Elucidating the Functional Roles of Helper and Cytotoxic T Cells in the Cell-Mediated Immune Responses of Olive Flounder (Paralichthys olivaceus).

In higher vertebrates, helper and cytotoxic T cells, referred to as CD4 and CD8 T lymphocytes, respectively, are mainly associated with adaptive immunity. The adaptive immune system in teleosts involves T cells equivalent to those found in mammals. We previously generated monoclonal antibodies (mAbs) against olive flounder (Paralichthys olivaceus) CD4 T cells, CD4-1 and CD4-2, and used these to describe the olive flounder's CD4 Tcell response during a viral infection. In the present study, we successfully produced mAbs against CD8 T lymphocytes and their specificities were confirmed using immuno-blotting, immunofluorescence staining, flow cytometry analysis andreverse transcription polymerase chain reaction (RT-PCR). The results showed that these mAbs are specific for CD8 T lymphocytes. We also investigated variations in CD4 and CD8 T cells populations, and analyzed the expression of immune-related genes expressed by these cells in fish infected with nervous necrosis virus or immunized with thymus dependent and independent antigens. We found that both CD4 and CD8 T lymphocyte populations significantly increased in these fish and Th1-related genes were up-regulated compared to the control group. Collectively, these findings suggest that the CD4 and CD8 T lymphocytes in olive flounder are similar to the helper and cytotoxic T cells found in mammals, and Th1 and cytotoxic immune responses are primarily involved in the early adaptive immune response against extracellular antigens.

Newly Identified AhR-Active Compounds in the Sediments of an Industrial Area Using Effect-Directed Analysis.

Effect-directed analysis was used to identify previously unidentified aryl hydrocarbon receptor (AhR) agonists in sediments collected from a highly industrialized area of Ulsan Bay, Korea. The specific objectives were to (i) investigate potent fractions of sediment extracts using the H4IIE-luc bioassay, (ii) determine the concentrations of known AhR agonists (polycyclic aromatic hydrocarbons (PAHs) and styrene oligomers (SOs)), (iii) identify previously unreported AhR agonists in fractions by use of GC-QTOFMS, and (iv) evaluate contributions of individual compounds to overall AhR-mediated potencies, found primarily in fractions containing aromatics with log Kow 5-8. Greater concentrations of PAHs and SOs were also found in those fractions. On the basis of GC-QTOFMS and GC-MSD analyses, 16 candidates for AhR agonists were identified in extracts of sediments. Of these, seven compounds, including 1-methylchrysene, benzo[j]fluoranthene, 3-methylchrysene, 5-methylbenz[a]anthracene, 11H-benzo[b]fluorene, benzo[b]naphtho[2,3-d]furan, and benzo[b]naphtho[2,1-d]thiophene, exhibited significant AhR activity. Relative potency values of newly identified AhR agonists were found to be greater than or comparable to that of benzo[a]pyrene (BaP). The potency balance analysis showed that newly identified AhR agonists explained 0.07-16% of bioassay-derived BaP-EQs. These chemicals were widely distributed in industrial sediments; thus, it is of immediate importance to conduct studies on sources and potential effects of those chemicals.

Evaluation of residual toxicity of hypochlorite-treated water using bioluminescent microbes and microalgae: Implications for ballast water management.

Total residual oxidants (TRO) in treated ballast water can produce various disinfection by-products (DBPs) depending on local conditions, such as salinity and organic matter content in water. Because TRO and DBPs are known to be harmful to aquatic organisms and humans, ecotoxicity tests have been proposed for screening the residual toxicity before discharging treated ballast water. In the present study, we aimed to address the decay rates and toxicity changes of TRO under various conditions in salinity, initial TRO concentrations, and residence time of TRO. In addition, the toxicological sensitivities of bioluminescent bacteria Vibrio fischeri and a commonly-used microalgae Skeletonema costatum relative to the residual toxicity of TRO and six selected DBPs were determined. Decay rate of TRO concentration increased as a function of salinity and was affected by the initial concentrations of TRO. Unexpectedly, significant bioluminescence inhibition was observed for hypochlorite-treated water at < 0.1 mg L-1 TRO (expressed as Cl2), which is a lower concentration than the maximum allowable discharge concentration (MADC) to marine waters established by the International Maritime Organization (IMO). The ecotoxicological thresholds of no observed effective concentration and median effect concentration for all tested DBPs were about 3-10 times lower for V. fischeri than for S. costatum. The results indicate that bioluminescent microbes possess an ecologically-relevant sensitivity to both TRO and DBPs in ballast water. In general, bioassay using V. fischeri was potentially more effective than microalgae for screening the total toxicity of TRO and DBPs in treated ballast water, especially given that ballast water usually contains a highly variable and complex mixture of toxicants.

Medialis pedis flap for reconstruction of weight bearing heel.

BACKGROUND: Among the various flaps available for the reconstruction of the heel, a medial plantar flap has been widely accepted as the most ideal. This flap, however, involves the medial plantar nerve and its cutaneous branches, which may lead to postoperative hyperesthesia and dual sensation. The purpose of this report was to report the outcomes of the use of the medialis pedis flap for the coverage of weight bearing heel soft tissue defect. PATIENTS AND METHODS: A total of 8 patients who had undergone reconstruction of the weight bearing heel with the medialis pedis flap were enrolled for this study. There were 6 male and 2 female patients and the mean age was 46 years. The causes of the defects included pressure sore, crushing injury and malignant melanoma. The mean size of the defects was 3 × 4 cm. Five cases were reconstructed with island flaps and 3 were covered with free flaps. RESULTS: The mean size of the flaps was 3×5 cm. All flaps survived. One case developed arterial insufficiency and was treated with a vein graft. Ambulation in normal shoes was possible in all the patients. Seven cases did not report pain, but 1 case complained of mild pain. No case reported complications including pain at the donor site, ulcerations, sensory loss, hyperesthesia, or sensory disturbance. The mean follow-up period was 14.4 months. CONCLUSIONS: The medialis pedis flap may be considered a useful flap for the reconstruction of soft tissue defects smaller than 5 cm in the weight bearing heel.

Relationship between abstract thinking and eye gaze pattern in patients with schizophrenia.

BACKGROUND: Effective integration of visual information is necessary to utilize abstract thinking, but patients with schizophrenia have slow eye movement and usually explore limited visual information. This study examines the relationship between abstract thinking ability and the pattern of eye gaze in patients with schizophrenia using a novel theme identification task. METHODS: Twenty patients with schizophrenia and 22 healthy controls completed the theme identification task, in which subjects selected which word, out of a set of provided words, best described the theme of a picture. Eye gaze while performing the task was recorded by the eye tracker. RESULTS: Patients exhibited a significantly lower correct rate for theme identification and lesser fixation and saccade counts than controls. The correct rate was significantly correlated with the fixation count in patients, but not in controls. CONCLUSIONS: Patients with schizophrenia showed impaired abstract thinking and decreased quality of gaze, which were positively associated with each other. Theme identification and eye gaze appear to be useful as tools for the objective measurement of abstract thinking in patients with schizophrenia.

The effect of simulated auditory hallucinations on daily activities in schizophrenia patients.

BACKGROUND: Auditory hallucinations often influence schizophrenia patients in many aspects. In order to develop effective behavioral interventions for overcoming enduring auditory hallucinations, it is necessary to understand how the annoying symptom affects the daily lives of the patients. This study evaluated the effect of hearing unusual voices on performing the activities of daily life in schizophrenia patients. METHODS: Eighteen hallucinating patients, 18 nonhallucinating patients and 20 normal controls performed the virtual daily-life task of packing 8 items for travel under 3 conditions: (1) without unusual voices and without avatars, (2) with unusual voices and without avatars and (3) with unusual voices and with avatars. Task completion time and the number of times the packing list was checked were recorded as a measure of the task performance. RESULTS: When exposed to unusual voices without avatars, hallucinating patients checked the packing list fewer times than nonhallucinating patients, and they required longer to complete the task, as positive and negative symptoms were worse. Subjective responses to unusual voices were stronger in hallucinating patients than in nonhallucinating patients. CONCLUSIONS: Daily-life activities of hallucinating patients may be less easily influenced by odd auditory stimuli in a nonsocial situation than those of nonhallucinating patients; however, hallucinating patients may feel more strongly affected by unusual voices. To better evaluate and thereby understand the difficulties faced by hallucinating patients in their daily life, the discrepancies between objective and subjective measures as well as social situations should be taken into consideration.

Evaluation of metal contamination in brackish area sediments South Korea, using receiver operation characteristic curve.

Brackish areas are where freshwater and seawater meet and possess high geographical and biological importance. However, no unified evaluation method exists for brackish sediments. Therefore, this study applies both the fresh water-sediment quality guidelines (F-SQGs) and the marine-sediment quality guidelines (M-SQGs) to evaluate metal contamination in brackish areas of Korea. The predicted reliability was examined using a receiver operation characteristic (ROC) curve. In the threshold effect level (TEL) evaluation of F-SQGs and M-SQGs, some metals (Cu, Zn, Hg, and Cd) showed significant differences according to guideline characteristics. The ROC curve showed that the predicted reliability of F-SQGs was 97.8 %, which was higher than M-SQGs (91.7 %). From the results of TEL evaluation and ROC curve prediction, F-SQGs are more suitable for the evaluation of brackish sediments in South Korea than M-SQGs.

Optimal timing of percutaneous transhepatic gallbladder drainage and subsequent laparoscopic cholecystectomy according to the severity of acute cholecystitis.

Backgrounds/Aims: The optimal timing of percutaneous transhepatic gallbladder drainage (PTGBD) and subsequent laparoscopic cholecystectomy (LC) according to the severity of acute cholecystitis (AC) has not been established yet. Methods: This single-center, retrospective study included 695 patients with grade I or II AC without common bile duct stones who underwent PTGBD and subsequent LC between January 2010 and December 2019. Difficult surgery (DS) (open conversion, subtotal cholecystectomy, adjacent organ injury, transfusion, operation time ≥ 90 minutes, or estimated blood loss ≥ 100 mL) and poor postoperative outcome (PPO) (postoperative hospital stay ≥ 7 days or Clavien-Dindo grade ≥ II postoperative complication) were defined to comprehensively evaluate intraoperative and postoperative outcomes, respectively. Results: Of 695 patients, 403 had grade I AC and 292 had grade II AC. According to the receiver operating characteristic curve and multivariate logistic regression analyses, an interval from symptom onset to PTGBD of > 3.5 days and an interval from PTGBD to LC of > 7.5 days were significant predictors of DS and PPO, respectively, in grade I AC. In grade II AC, the timing of PTGBD and subsequent LC were not statistically related to DS or PPO. Conclusions: In grade I AC, performing PTGBD within 3.5 days after symptom onset can reduce surgical difficulties and subsequently performing LC within 7.5 days after PTGBD can improve postoperative outcomes. In grade II AC, early PTGBD cannot improve the surgical difficulty. In addition, the timing of subsequent LC is not correlated with surgical difficulties or postoperative outcomes.

Effects of torrefaction on product distribution and quality of bio-oil from food waste pyrolysis in N2 and CO2.

Waste food utilization to produce bio-oil through pyrolysis has received increasing attention. The feedstock can be utilized more efficiently as its properties are upgraded. In this work, the mixed food waste (MFW) was pretreated via torrefaction at moderate temperatures (250-275 °C) under an inert atmosphere before fast pyrolysis. The pyrolysis of torrified MFW (T-MFW) was performed in a bubbling fluidized-bed reactor (FBR) to study the influence of torrefaction on the pyrolysis product distribution and bio-oil compositions. The highest liquid yield of 39.54 wt% was observed at a pyrolysis temperature of 450℃. The torrefaction has a significant effect on the pyrolysis process of MFW. After torrefaction, the higher heating values (HHVs) of the pyrolysis bio-oils (POs) ranged from 31.51 to 34.34 MJ/kg, which were higher than those of bio-oils from raw MFW (27.69-31.58 MJ/kg). The POs mainly contained aliphatic hydrocarbons (alkenes and ketones), phenolic, and N-containing derivatives. The pyrolysis of T-MFW was also carried out under the CO2 atmosphere. The application of CO2 as a carrier gas resulted in a decrease in the liquid yield and an increase in the gas product yield. In addition, the carbon and nitrogen content of POs increased, whereas the oxygen was reduced via the release of moisture and CO. Using CO2 in pyrolysis inhibited the generation of nitriles derivatives in POs, which are harmful to the environment. These results indicated that the application of CO2 to the thermal treatment of T-MFW could be feasible in energy production as well as environmental pollution control.

Anhedonia Relates to the Altered Global and Local Grey Matter Network Properties in Schizophrenia.

Anhedonia is one of the major negative symptoms in schizophrenia and defined as the loss of hedonic experience to various stimuli in real life. Although structural magnetic resonance imaging has provided a deeper understanding of anhedonia-related abnormalities in schizophrenia, network analysis of the grey matter focusing on this symptom is lacking. In this study, single-subject grey matter networks were constructed in 123 patients with schizophrenia and 160 healthy controls. The small-world property of the grey matter network and its correlations with the level of physical and social anhedonia were evaluated using graph theory analysis. In the global scale whole-brain analysis, the patients showed reduced small-world property of the grey matter network. The local-scale analysis further revealed reduced small-world property in the default mode network, salience/ventral attention network, and visual network. The regional-level analysis showed an altered relationship between the small-world properties and the social anhedonia scale scores in the cerebellar lobule in patients with schizophrenia. These results indicate that anhedonia in schizophrenia may be related to abnormalities in the grey matter network at both the global whole-brain scale and local-regional scale.

The relationship between ambivalence, alexithymia, and salience network dysfunction in schizophrenia.

Ambivalence in schizophrenia is worth investigating its association with salience processing and alexithymia using functional MRI. Twenty-two patients with schizophrenia and 22 healthy controls were scanned during the ambivalence task of matching picture (ambivalent, positive and negative) and word (positive and negative) stimuli, and the Toronto Alexithymia Scale (TAS) was rated. Patients exhibited decreased activity in the anterior cingulate cortex (ACC) and insula compared to controls, and ACC activity in the ambivalent condition was negatively correlated with the TAS score in patients. Ambivalence in schizophrenia may be based on salience network dysfunction, and this disturbance may be related to alexithymia.

Anti-Inflammatory Effect of Artemisia argyi on Ethanol-Induced Gastric Ulcer: Analytical, In Vitro and In Vivo Studies for the Identification of Action Mechanism and Active Compounds.

Artemisia argyi is widely used as traditional medicine in East Asia. However, its effects against inflammation and gastric ulcers have not been reported yet. We analyzed anti-inflammatory activity and its molecular mechanisms of A. argyi using RAW264.7 cells line, then evaluated the curative efficacy in rats with acute gastric ulcers. Nitric oxide and IL-6 production was measured using Griess reagent and an ELISA kit. Inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and mucin (MUC)1, MUC5AC, and MUC6 mRNA were determined by SYBR Green or Taqman qRT-PCR methods. The phosphorylation of ERK, JNK, p38, and c-Jun protein were detected by western blotting. RW0117 inhibited LPS-induced NO and IL-6 production. The mRNA levels of iNOS and IL-6 were strongly suppressed. The phosphorylation of ERK, JNK, and c-Jun decreased by treatment with RW0117. Oral administration of RW0117 recovered the amount of mucin mRNA and protein level that was decreased due to gastric ulcers by HCl-EtOH. A. argyi exhibited strong anti-inflammatory effects and contributed to the modulation of HCl-EtOH-induced gastric ulcer in rats.

Fatty Acid Derivatives Isolated from the Oil of Persea americana (Avocado) Protects against Neomycin-Induced Hair Cell Damage.

Avocado oil is beneficial to human health and has been reported to have beneficial effects on sensorineural hearing loss (SNHL). However, the compounds in avocado oil that affect SNHL have not been identified. In this study, we identified 20 compounds from avocado oil, including two new and 18 known fatty acid derivatives, using extensive spectroscopic analysis. The efficacy of the isolated compounds for improving SNHL was investigated in an ototoxic zebrafish model. The two new compounds, namely (2R,4R,6Z)-1,2,4-trihydroxynonadec-6-ene and (2R,4R)-1,2,4-trihydroxyheptadecadi-14,16-ene (compounds 1 and 2), as well as compounds 7, 9, 14, 17 and 19 showed significant improvement in damaged hair cells in toxic zebrafish. These results led to the conclusion that compounds from avocado oil as well as oil itself have a regenerative effect on damaged otic hair cells in ototoxic zebrafish.

Expression profiling of calcium induced genes in cultured human keratinocytes.

Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. To examine the gene expression profile in calcium-induced keratinocyte differentiation, we constructed a normalized cDNA library using mRNA isolated from these calcium-treated keratinocytes. After sequencing about 10,000 clones, we were able to obtain 4,104 independent genes. They consisted of 3,699 annotated genes and 405 expressed sequence tags (ESTs). Some were the genes involved in constituting epidermal structures and others were unknown genes that are probably associated with keratinocytes. In particular, we were able to identify genes located at the chromosome 1q21, the locus for the epidermal differentiation complex, and 19q13.1, another probable locus for epidermal differentiation-related gene clusters. One EST located at the chromosome 19q13.1 showed increased expression by calcium treatment, suggesting a novel candidate gene relevant to keratinocyte differentiation. These results demonstrate the complexity of the transcriptional profile of keratinocytes, providing important clues on which to base further investigations of the molecular events underlying keratinocyte differentiation.

The Relationship between Neuropsychiatric Symptoms and Default-Mode Network Connectivity in Alzheimer's Disease.

OBJECTIVE: Neuropsychiatric symptoms of dementia are prevalent and extremely burdening for the patient and caregivers, but the underlying mechanism of these symptoms has not been investigated. This study aimed to investigate the relationship between neuropsychiatric symptoms and default-mode functional connectivity in Alzheimer's disease. METHODS: Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Functional magnetic resonance imaging was conducted on seventy patients with Alzheimer's disease during rest. We conducted a seed-based functional connectivity analysis to identify anterior and posterior default-mode networks (DMN). Seeds were the medial prefrontal cortex (Montreal Neurological Institute 12, 51, 36; seed radius=3 mm) for the anterior DMN and the precuneus (Montreal Neurological Institute -6, -63, 27; seed radius=3 mm) for the posterior DMN We then correlated the scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective, and psychosis syndrome) with maps of connectivity in the default-mode network. RESULTS: There was a significant correlation between decreased connectivity in the medial prefrontal cortex of the anterior defaultmode network and hyperactivity (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) syndrome (p<0.05, family wise error cluster-level corrected). CONCLUSION: Our study demonstrated that hyperactivity syndrome is related to hypoconnected default-mode network in Alzheimer's disease. This finding suggests that specific network alterations are associated with certain neuropsychiatric syndromes.

Anti-Obesity Effect of DKB-117 through the Inhibition of Pancreatic Lipase and α-Amylase Activity.

This study sought to evaluate the effects of Phaseolus multiflorus var. albus Bailey extract (PM extract) and Pleurotus eryngii var. ferulae extract (PF extract) on the inhibition of digestive enzymes and to confirm the anti-obesity effect of DKB-117 (a mixture of PM extract and PF extract) in digestive enzyme inhibition in a mouse model of obesity induced by a high-fat diet. In in vitro studies, PM extract and PF extract have increased dose-dependent inhibitory activity on α-amylase (Inhibitory concentration (IC50 value: 6.13 mg/mL)) and pancreatic lipase (IC50 value; 1.68 mg/mL), respectively. High-fat diet-induced obese mice were orally administered DKB-117 extracts at concentrations of 100, 200, and 300 mg/kg/day, while a positive control group was given orlistat (pancreatic lipase inhibitor) and Garcinia cambogia (inhibiting the enzymes needed to synthesize carbohydrates into fat) at concentrations of 40 and 200 mg/kg/day, respectively, for eight weeks. As a result, body weight, fat mass (total fat mass, abdominal fat, and subcutaneous fat) detected with microcomputed tomography, fat mass (abdominal fat and inguinal fat) after an autopsy, and liver triglyceride levels were decreased significantly in the DKB-117 (300 mg/kg/day) group compared to those in the HFD control group. Additionally, we obtained results indicating that the presence of carbohydrates was found more in the DKB-117-300 (300 mg/kg/day) group than in the HFD control group. These data clearly show that DKB-117 extracts are expected to have an anti-obesity effect through a complex mechanism that promotes carbohydrate release through the inhibition of carbohydrate-degrading enzymes while blocking lipid absorption through lipase inhibition.

A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum.

This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0-9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

Korean Medication Algorithm for Schizophrenia 2019, Second Revision: Treatment of Psychotic Symptoms.

Objective: In 2001, the Korean College of Neuropsychopharmacology and the Korean Society for Schizophrenia Research developed the Korean Medication Algorithm Project for Schizophrenia (KMAP-SPR 2001, revised 2006) through a consensus of expert opinion. The present study was carried out to support the second revision of the KMAP-SPR. Methods: Based on clinical guidelines and studies on the treatment of psychotic symptoms in schizophrenia, the Executive committee completed a draft of KMAP-SPR 2019. To obtain an expert consensus, a Review committee of 100 Korean psychiatrists was formed and 69 responded to a 30-item questionnaire. Based on their responses, the KMAP-SPR 2019 was finalized. Results: The revised schizophrenia algorithm now consists of 5 stages. At Stage 1, monotherapy with atypical antipsychotics was recommended by expert reviewers as the first-line strategy. At Stage 2, most reviewers recommended the use of typical or atypical antipsychotic drugs not used at Stage 1. At Stage 3, many reviewers agreed with the administration of clozapine. At Stage 4, a combination of clozapine and other agents such as antipsychotics, mood stabilizers, antidepressants, or electroconvulsive therapy was recommended. At Stage 5, most reviewers recommended combined treatment with an antipsychotic other than clozapine; and a mood stabilizer, antidepressant, or electroconvulsive therapy. At any stage, prescribing long-acting injectable antipsychotics at the discretion of the clinician was recommended. Conclusion: Compared with previous versions, the KMAP-SPR 2019 now recommends using clozapine earlier in treatment- refractory schizophrenia. In addition, the use of long-acting injectable antipsychotics is now considered to be available at any stage.

Effects of polluted and non-polluted suspended sediments on the oxygen consumption rate of olive flounder, Paralichthys olivaceus.

The potential ecological impacts of elevated suspended sediments (SS) in coastal areas due to human activities remain unclear. In particular, physiological response of benthic fish to SS exposure in polluted environment has not been documented. We determined sub-lethal toxicity of polluted and non-polluted SS to olive flounder. Test organism was exposed to varying concentrations of SS (0-4000 mg L-1) and real-time oxygen consumption rate (OCR) was measured for 12 h. The early-juvenile was sensitive to SS, particularly at >500 mg L-1, but late-juvenile was tolerant up to 4000 mg SS L-1. Metal polluted SS (HQmetal > 1) increased OCR in general, particularly at >1000 SS mg L-1. Combined effect of copper and SS exposure on fish was either synergistic or antagonistic. Overall, potential adverse effect of polluted SS on fish greatly varied at different life stage and/or by metal pollution gradients.

Protective Mechanisms of Avocado Oil Extract Against Ototoxicity.

Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-α or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-α was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.