Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination.

The Mpk1 MAPK of the yeast cell wall integrity pathway uses a noncatalytic mechanism to activate transcription of stress-induced genes by recruitment of initiation factors to target promoters. We show here that Mpk1 additionally serves a function in transcription elongation that is also independent of its catalytic activity. This function is mediated by an interaction between Mpk1 and the Paf1 subunit of the Paf1C elongation complex. A mutation in Paf1 that blocks this interaction causes a specific defect in transcription elongation of an Mpk1-induced gene, which results from Sen1-dependent premature termination through a Nab3-binding site within the promoter-proximal region of the gene. Our findings reveal a regulatory mechanism in which Mpk1 overcomes transcriptional attenuation by blocking recruitment of the Sen1-Nrd1-Nab3 termination complex to the elongating polymerase. Finally, we demonstrate that this mechanism is conserved in an interaction between the human ERK5 MAPK and human Paf1.

Sex Differences in Dietary Sodium evoked NCC Regulation and Blood Pressure in Male and Female Sprague Dawley, Dahl Salt-Resistant and Dahl Salt-Sensitive Rats.

Hypertension affects approximately 1 in 2 US adults and sex plays an important role in the pathogenesis of hypertension.​ The sodium chloride cotransporter (NCC), regulated by a kinase network including with-no-lysine kinases (WNK) 1 and WNK4, STE20/SPS1-related proline alanine rich kinase (SPAK), and oxidative stress response 1 (OxSR1) is critical to sodium reabsorption and blood pressure regulation. Dietary salt differentially modulates the NCC in salt-sensitive and salt-resistant rats, in part by modulation of WNK/SPAK/OxSR1 signaling. In these studies, we tested the hypothesis that sex-dependent differences in NCC regulation contribute to the development of the salt sensitivity of blood pressure using male and female Sprague Dawley, Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. In normotensive salt resistant SD and DSR rats a high salt diet evoked significant decreases in NCC activity, expression, and phosphorylation. In males these changes were associated with no change in WNK1 expression and a decrease in WNK4 levels and suppression of SPAK/OxSR1 expression and phosphorylation. In contrast in females decreased NCC activity associated with suppression of SPAK/OxSR1 expression and phosphorylation. In hypertensive DSS rats the ability of females to suppress NCC (in opposition to males) via a SPAK/OxSR1 mechanism likely contributes to their lower magnitude of salt-sensitive hypertension. Collectively our findings support the existence of sex differences in male versus female rats with NCC regulation during dietary salt intake involving suppression of WNK4 expression in male rats only and the involvement of SPAK/OxSR1 signaling in both males and females.

A Bee Trp-Arg Dense Peptide with Antiproliferation Efficacy against the Prostate Cancer Cell Line DU145.

Prostate cancer accounts for 14% of male cancer-related fatalities in the UK. Given the challenges associated with hormone-based therapies in the context of androgen-independent prostate cancer, there is an imperative need for research into anticancer drugs. N0821, a peptide belonging to the Trp-Arg dense region and derived from the homologous region of various bee species, shows substantial potential for an anticancer effect. Both MTT assays and 3D spheroid assays were conducted to substantiate its antiproliferation potential and strongly indicated the antiproliferation effect of N0820 (WWWWRWWRKI) and N0821 (YWWWWRWWRKI). Notably, the mechanism underlying this effect is related to the downregulation of CCNA2 and the upregulation of CCNE1. Cell cycle arrest results from the reduction of CCNA2 in the S/G2 phase, leading to the accumulation of CCNE1. Our peptides were predicted to make an α-helix structure. This can act as an ion channel in the cell membrane. Therefore, we analyzed genes implicated in the influx of calcium ions into the mitochondria. Trp-Arg dense-region peptides are known for their antibacterial properties in targeting cell membranes, making the development of resistance less likely. Hence, further research in this area is essential and promising.

FUS-induced neurotoxicity is prevented by inhibiting GSK-3ß in a Drosophila model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS)-linked mutations in fused in sarcoma (FUS) lead to the formation of cytoplasmic aggregates in neurons. They are believed to play a critical role in the pathogenesis of FUS-associated ALS. Therefore, the clearance and degradation of cytoplasmic FUS aggregates in neurons may be considered a therapeutic strategy for ALS. However, the molecular pathogenic mechanisms behind FUS-associated ALS remain poorly understood. Here, we report GSK-3ß as a potential modulator of FUS-induced toxicity. We demonstrated that RNAi-mediated knockdown of Drosophila ortholog Shaggy in FUS-expressing flies suppresses defective phenotypes, including retinal degeneration, motor defects, motor neuron degeneration and mitochondrial dysfunction. Furthermore, we found that cytoplasmic FUS aggregates were significantly reduced by Shaggy knockdown. In addition, we found that the levels of FUS proteins were significantly reduced by co-overexpression of Slimb, a F-box protein, in FUS-expressing flies, indicating that Slimb is critical for the suppressive effect of Shaggy/GSK-3ß inhibition on FUS-induced toxicity in Drosophila. These findings revealed a novel mechanism of neuronal protective effect through SCFSlimb-mediated FUS degradation via GSK-3ß inhibition, and provided in vivo evidence of the potential for modulating FUS-induced ALS progression using GSK-3ß inhibitors.

Bilateral Visual Impairment following Combination Chemotherapy with Carboplatin in Patients with Small Cell Lung Cancer: A Case Report.

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.

Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.

Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase (MAPK) family, is involved in key cellular processes. However, overexpression and upregulation of ERK5 have been reported in various cancers, and ERK5 is associated with almost every biological characteristic of cancer cells. Accordingly, ERK5 has become a novel target for the development of anticancer drugs as inhibition of ERK5 shows suppressive effects of the deleterious properties of cancer cells. Herein, we report the synthesis and identification of a novel ERK5 inhibitor, MHJ-627, and verify its potent anticancer efficacy in a yeast model and the cervical cancer HeLa cell line. MHJ-627 successfully inhibited the kinase activity of ERK5 (IC50: 0.91 µM) and promoted the mRNA expression of tumor suppressors and anti-metastatic genes. Moreover, we observed significant cancer cell death, accompanied by a reduction in mRNA levels of the cell proliferation marker, proliferating cell nuclear antigen (PCNA), following ERK5 inhibition due to MHJ-627 treatment. We expect this finding to serve as a lead compound for further identification of inhibitors for ERK5-directed novel approaches for oncotherapy with increased specificity.

Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a drosophila homolog of FUS, in the brain.

Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, GstO2 knockdown in Drosophila led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. Drosophila Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after GstO2 knockdown in vivo. Downregulation of GstO2 decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of Drosophila.

Filipendula glaberrima Nakai extract inhibits the bacterial infection by induction of HBD2 and HBD3 expression, and reduction of the inflammatory activity.

Defensins and inflammation are innate immune barriers of the body against infectious pathogens. Searching for a compound that can inhibit infectious diseases by affecting human ß-defensin (HBD) and proinflammatory cytokines is the new trend in research to control bacterial infection. The aim of this study is to provide a natural compound, Filipendula glaberrima Nakai extract (FGE), which is able to induce the expression of an antimicrobial defensin as well as reduce inflammation. FGE induced the expression of HBD2 and HBD3 through activating both p38 and NF-κB signaling pathways. Furthermore, FGE inhibited the expression of TNF-α and IL-6 via p38 and NF-κB pathways in Staphylococcus aureus-stimulated THP1 cells. Injection of FGE alleviated cutaneous erythema and swelling caused by S. aureus injection in mice ears. Taken together, FGE could reduce bacterial infection by inducing the expression of defensin and anti-inflammatory activity.

Alpinia japonica extract induces apoptosis of hepatocellular carcinoma cells through G0/G1 cell cycle arrest and activation of JNK.

Hepatic cancer was the third most prevalent cause of cancer-related death worldwide in 2018, and its incidence is increasing. While therapeutic agents for hepatic cancer have improved, these agents can cause serious side effects, including damage to healthy tissues. To overcome this limitation, more than 3,000 plants have been used globally as common alternatives for cancer treatment. The anti-cancer activity of Alpinia japonica, one of the traditional herbal medicines (Korean name: Kkot-yang-ha), was investigated. Water extract of A. japonica (AJ) decreased the cell viability of hepatic cancer cells. AJ extract showed greater than 70% loss of mitochondrial potential in HepG2 cells as demonstrated by JC-1 staining. Apoptosis was induced by treatment with AJ extract as shown through FACS analysis, and G0/G1 phase arrest of 76.66% HepG2 cells was confirmed through cell cycle analysis and quantitative RT-PCR. Improper regulation of ERK1/2 might contribute to cell death, and JNK activation is necessary for apoptosis induced by stress stimuli. AJ extract stimulated the phosphorylation of JNK and ERK1/2, mitogen-activated protein kinases (MAPKs), in HepG2 cells. AJ extract has anticancer activity by inhibiting cell cycle progression, leading to apoptosis of hepatic cancer cells. This extract could potentially be used as a therapeutic agent for hepatic cancer.

PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. RESULTS: Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). CONCLUSION: A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

Peripapillary microvasculature changes after vitrectomy in epiretinal membrane via swept-source OCT angiography.

PURPOSE: To evaluate the peripapillary microvasculature changes in patients with epiretinal membrane (ERM) following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling using swept-source optical coherence tomography angiography (SS-OCTA). METHOD: Medical records and multimodal imaging data of 33 eyes after PPV for ERM were retrospectively reviewed. Peripapillary SS-OCTA images of 6×6 mm2 were recorded at at pre- and post-operatively every 6 months for 1 year. A semi-automated method was used to analyzed SS-OCTA images, excluding the optic disc area, using the MATLAB software. The peripapillary vessel density (pVD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) was quantified in four quadrants (superior, inferior, nasal and temporal). RESULT: The mean pVD in SCP and DCP decreased at 6- and 12-months follow-up. In sectoral analysis, superior, inferior, and temporal quadrants pVD in SCP and DCP were significantly reduced at 1 year after vitrectomy (all p < 0.05). Meanwhile, inferior quadrants pVD in SCP and DCP showed the earliest significant reduction at 6-months (p = 0.022 and 0.048, respectively). A reduction of post-operative mean pVD in DCP was significantly greater in patients with diabetic retinopathy (p = 0.043). CONCLUSION: Peripapillary capillary density significantly decreased after surgical removal of ERM. Vitrectomy with ILM peeling can cause peripapillary microvascular damage starting in inferior sector.

Optical coherence tomography angiography biomarkers in a bi-monthly maintenance dosing aflibercept in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen. METHODS: This prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment. RESULTS: Patients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017). CONCLUSIONS: The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD. TRIAL REGISTRATION: The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).

Perifoveal Microvascular Changes following Internal Limiting Membrane Peeling Surgery for Epiretinal Membrane and Macular Hole.

INTRODUCTION: The aim of the study was to evaluate perifoveal microvasculature changes following pars plana vitrectomy with internal limiting membrane peeling for the epiretinal membrane (ERM) and macular hole (MH). METHODS: This retrospective study included 59 eyes from 59 patients. Subjects were divided into two groups: an ERM group (n = 43) and an MH group (n = 16) based on the initial diagnosis. Swept-source optical coherence tomography angiography (SS-OCTA) was performed in the macular area, pre- and postoperatively. Perifoveal microvascular changes were calculated using MATLAB from the 6 × 6 mm SS-OCTA images, excluding the foveal avascular zone. Pre- and postoperative perifoveal vessel densities (pfVDs) were separately analyzed in six sectors (superior, superotemporal, inferotemporal, inferior, inferonasal, and superonasal) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The baseline characteristics and other clinical factors were compared between the ERM and MH groups. RESULTS: The postoperative best-corrected visual acuity significantly improved in both groups (p < 0.05). One year after surgery, the pfVD in the SCP of the ERM group significantly decreased in the inferotemporal sector (p = 0.049). The postoperative pfVD in the DCP of the MH group significantly decreased in temporal sectors (p < 0.05). The postoperative mean pfVD in the SCP in the MH group was significantly lower than that in the ERM group (p = 0.003). The presence of a dissociated optic nerve fiber layer (DONFL) was 75% in the MH group and 22% in the ERM group (p = 0.018). The correlation between the pfVD and DONFL was not statistically significant. CONCLUSION: Postoperative pfVD reduction in the temporal sector, a corresponding area in which DONFL is present after MH surgery, was significantly observed. After vitreoretinal surgery in MH patients, OCTA may serve as a useful tool for monitoring perifoveal microvascular changes, especially in temporal sectors.

The Unknown Abnormal Condition Monitoring Method for Pumped-Storage Hydroelectricity.

Pumped-storage hydroelectricity (PSH) is a facility that stores energy in the form of the gravitational potential energy of water by pumping water from a lower to a higher elevation reservoir in a hydroelectric power plant. The operation of PSH can be divided into two states: the turbine state, during which electric energy is generated, and the pump state, during which this generated electric energy is stored as potential energy. Additionally, the condition monitoring of PSH is generally challenging because the hydropower turbine, which is one of the primary components of PSH, is immersed in water and continuously rotates. This study presents a method that automatically detects new abnormal conditions in target structures without the intervention of experts. The proposed method automatically updates and optimizes existing abnormal condition classification models to accommodate new abnormal conditions. The performance of the proposed method was evaluated with sensor data obtained from on-site PSH. The test results show that the proposed method detects new abnormal PSH conditions with an 85.89% accuracy using fewer than three datapoints and classifies each condition with a 99.73% accuracy on average.

Continuous Structural Displacement Monitoring Using Accelerometer, Vision, and Infrared (IR) Cameras.

With the rapid development of computer vision, vision cameras have been used as noncontact sensors for structural displacement measurements. However, vision-based techniques are limited to short-term displacement measurements because of their degraded performance under varying illumination and inability to operate at night. To overcome these limitations, this study developed a continuous structural displacement estimation technique by combining measurements from an accelerometer with vision and infrared (IR) cameras collocated at the displacement estimation point of a target structure. The proposed technique enables continuous displacement estimation for both day and night, automatic optimization of the temperature range of an infrared camera to ensure a region of interest (ROI) with good matching features, and adaptive updating of the reference frame to achieve robust illumination-displacement estimation from vision/IR measurements. The performance of the proposed method was verified through lab-scale tests on a single-story building model. The displacements were estimated with a root-mean-square error of less than 2 mm compared with the laser-based ground truth. In addition, the applicability of the IR camera for displacement estimation under field conditions was validated using a pedestrian bridge test. The proposed technique eliminates the need for a stationary sensor installation location by the on-site installation of sensors and is therefore attractive for long-term continuous monitoring. However, it only estimates displacement at the sensor installation location, and cannot simultaneously estimate multi-point displacements which can be achieved by installing cameras off-site.

Development of a Real-Time 6-DOF Motion-Tracking System for Robotic Computer-Assisted Implant Surgery.

In this paper, we investigate a motion-tracking system for robotic computer-assisted implant surgery. Failure of the accurate implant positioning may result in significant problems, thus an accurate real-time motion-tracking system is crucial for avoiding these issues in computer-assisted implant surgery. Essential features of the motion-tracking system are analyzed and classified into four categories: workspace, sampling rate, accuracy, and back-drivability. Based on this analysis, requirements for each category have been derived to ensure that the motion-tracking system meets the desired performance criteria. A novel 6-DOF motion-tracking system is proposed which demonstrates high accuracy and back-drivability, making it suitable for use in computer-assisted implant surgery. The results of the experiments confirm the effectiveness of the proposed system in achieving the essential features required for a motion-tracking system in robotic computer-assisted implant surgery.

MSF Enhances Human Antimicrobial Peptide ß-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways.

Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human ß-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.

Effects of Stocking Density on Stress, Hematological Responses, and Growth of Black Rockfish Sebastes schlegelii.

The objective of the current study was to evaluate the effect of stocking density on juvenile Black Rockfish Sebastes schlegelii (average weight = 12 g) in terms of stress, hematological responses, and growth performance during a 4-month growth trial in a flow-through system. The initial stocking densities were 1.3 kg/m3 (low), 1.8 kg/m3 (medium), and 2.3 kg/m3 (high), and the final densities were 4.9 kg/m3 (low), 5.6 kg/m3 (medium), and 6.3 kg/m3 (high). At the end of the trial, the high stocking density significantly affected growth characteristics, levels of growth hormone and insulin-like growth factor 1, and hematological indices (hematocrit, red blood cell count, and hemoglobin level) compared to the medium and low stocking densities. The plasma cortisol and immunoglobulin-M levels were significantly higher at the high density than at the other two densities. Taken together, while the low and medium stocking densities (final densities of up to 5.6 kg/m3 ) did not affect stress and hematological indices or growth, the high stocking density (final density of 6.3 kg/m3 ) significantly impacted those variables, which suggests an allostatic load at that density. Thus, the use of a final stocking density less than 6.3 kg/m3 should be considered to avoid compromising the stress and health condition and growth of Black Rockfish at this size and temperature range.

Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of Trapa japonica) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet.

Background and Objectives: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. Materials and Methods: This study investigated the pharmacological effects of water chestnut (fruit of Trapa japonica) extracts (WC: 50-200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). Results: Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group. The WC (50 mg/kg)-administered group showed no significant improvements in diabetic complications. However, HFD-induced obesity and diabetes-related complications such as hyperlipidemia, diabetic nephropathy, nonalcoholic fatty liver disease (NAFLD), oxidative stress, activity of antioxidant defense systems, and gene expressions were significantly and dose-dependently inhibited and/or normalized by oral administration of WC (100 mg/kg and 200 mg/kg), particularly at a dose of 100 mg/kg. Conclusions: The results of this study suggest that WC at an appropriate dose could be used to develop an effective therapeutic drug or functional food for type II diabetes and various associated complications, including NAFLD.