[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

The Effect of Cr Addition on the Strength and High Temperature Oxidation Resistance of Y2O3 Dispersion Strengthened Mo Composites.

Y2O3 dispersion-strengthened Molybdenum (Mo) composites were prepared by the mechanical alloying of Mo and Y powders then consolidation by spark plasma sintering. The effects of Chromium (Cr) addition (0 wt. %, 5 wt. %, 10 wt. % and 15 wt. %, respectively) on the mechanical performance and high-temperature oxidation resistance of Mo-Y2O3 were investigated. The introduction of Cr had a significant influence on the mechanical property and oxidation resistance of the Mo-Y2O3 composite. The highest bending strength reached 932 MPa when the addition of Cr content was 5 wt. % (Mo-5Cr-1Y sample). This improvement is likely attributable to the dual mechanism of grain refinement and solid solution strengthening. Moreover, the Mo-5Cr-1Y sample showed the thinnest oxide layer thickness after high-temperature oxidation tests, and exhibited the best oxidation resistance performance compared with the other samples. First principle calculation reveals that Cr could improve the Mo-MoO3 interface bonding to prevent rapid spalling of the oxide layer. Meanwhile, Cr also facilitates the formation of the dense Cr2(MoO4)3 layer on the surface, which can inhibit further oxidation.

Tumor necrosis factor α1 decreases mucosal immune and antioxidant response in the midgut of hybrid fish (white crucian carp ♀ × red crucian carp ♂).

Tumor necrosis factor α1 (TNFα) is a pleiotropic cytokine involved in immune regulation and cellular homeostasis, but the crucial role of TNFα in fish gut remained unclear. The current study aimed to evaluate the immunoregulatory function of TNFα1 on gut barrier in a novel hybrid fish (WR), which was produced by crossing white crucian carp (Carassius cuvieri, ♀) with red crucian carp (Carassius auratus red var, ♂). In this study, WR-tnfα1 sequence was identified, and a high-level expression was detected in the intestine. Elevated levels of WR-tnfα1 expressions were detected in immune-related tissues and cultured fish cells on stimulation. The appearance of vacuolization and submucosal rupture was observed in TNFα1-treated midgut of WR, along with elevated levels of goblet cell atrophy, whereas no significant changes were detected in most expressions of tight-junction genes and mucin genes. In contrast, WR receiving gut perfusion with WR-TNFα1 showed a remarkable decrease in antioxidant status in midgut, whereas the expression levels of apoptotic genes and redox responsive genes increased sharply. These results suggested that TNFα1 could exhibit a detrimental effect on antioxidant defense and immune regulation in the midgut of WR.

Clinical knowledge-guided deep reinforcement learning for sepsis antibiotic dosing recommendations.

Sepsis is the third leading cause of death worldwide. Antibiotics are an important component in the treatment of sepsis. The use of antibiotics is currently facing the challenge of increasing antibiotic resistance (Evans et al., 2021). Sepsis medication prediction can be modeled as a Markov decision process, but existing methods fail to integrate with medical knowledge, making the decision process potentially deviate from medical common sense and leading to underperformance. (Wang et al., 2021). In this paper, we use Deep Q-Network (DQN) to construct a Sepsis Anti-infection DQN (SAI-DQN) model to address the challenge of determining the optimal combination and duration of antibiotics in sepsis treatment. By setting sepsis clinical knowledge as reward functions to guide DQN complying with medical guidelines, we formed personalized treatment recommendations for antibiotic combinations. The results showed that our model had a higher average value for decision-making than clinical decisions. For the test set of patients, our model predicts that 79.07% of patients will achieve a favorable prognosis with the recommended combination of antibiotics. By statistically analyzing decision trajectories and drug action selection, our model was able to provide reasonable medication recommendations that comply with clinical practices. Our model was able to improve patient outcomes by recommending appropriate antibiotic combinations in line with certain clinical knowledge.

Cloning, expression and functional characterization of recombinant tumor necrosis factor α1 (TNFα1) from white crucian carp in gut immune regulation.

TNFα is one of important cytokines belonging to TNF superfamily, which can exhibit a pleiotropic effect in immune modulation, homeostasis as well as pathogenesis. However, its immunoregulatory function on mucosal immunity in fish gut are still unclear. In this study, we aimed to investigated the immunoregulatory role of TNFα1 in midgut of white crucian carp (WCC). WCC-TNFα1 sequence and its deduced structure were firstly identified in WCC. Then, tissue-specific analysis revealed that high-level WCC-TNFα1 expression was detected in gill. After Aeromonas hydrophila and lipopolysaccharide (LPS) stimulated, increased trends of WCC-TNFα1 expressions were detected in immune-related tissues and cultured fish cells, respectively. WCC anal-intubated with WCC-TNFα1 fusion protein showed the increased levels of edema and fuzzy appearance in impaired villi, along with atrophy and reduction of goblet cells (GC). Moreover, the expression levels of tight junction (TJ) genes and mucin genes were consistently lower than those of the control (P < 0.05). WCC-TNFα1 treatment could sharply decrease antioxidant status in midgut, while the expression levels of caspase (CASP) genes, unfolded protein response (UPR) genes and redox response genes increased dramatically. Our results suggested that WCC-TNFα1 could exhibit a detrimental effect on antioxidant and mucosal immune regulation in midgut of WCC.

Upregulation of oxidative stress by triphenyl phosphate (TPhP) exposure causes antioxidant insult and apoptotic process in Epithelioma papulosum cyprini (EPC) cells.

Triphenyl phosphate (TPhP) is the predominant compound of organophosphate flame retardants (OPFRs), which can elicit a toxicological effect on physiological response and tissue development of fish. In this study, we investigated the effect of TPhP exposure on cell viability, antioxidant capacities, and apoptosis in EPC cells. Current study revealed that TPhP exposure could decrease cell viability and promote intracellular oxidative stress in EPC cells. In addition, high-dose TPhP exposure could facilitate antioxidant insults and cause mitochondrial collapse in a dose-dependent manner, along with increased gene expressions involved in apoptosis and unfolded protein response (UPR). These results indicated that reactive oxygen species (ROS)-induced cytotoxic stress and cell death were involved in antioxidant insults and apoptotic activation in TPhP-exposed fish cells.

Alteration of synergistic immune response in gut-liver axis of white crucian carp (Carassius cuvieri) after gut infection with Aeromonas hydrophila.

Aeromonas hydrophila can pose a great threat to the survival of farmed fish. In current study, we investigated the pathological characteristics and immune response in gut-liver axis of white crucian carp (WCC) upon gut infection. WCC anally intubated with A. hydrophila exerted a tissue deformation in damaged midgut with elevated levels of goblet cells along with a significant decrease in tight junction proteins and villi length-to-width ratios. In addition, immune-related gene expressions and antioxidant properties increased dramatically in gut-liver axis of WCC following gut infection with A. hydrophila. These results highlighted the immune modulation and redox alteration in gut-liver axis of WCC in response to gut infection.

Gut-liver immune and redox response in hybrid fish (Carassius cuvieri ♀ × Carassius auratus red var. ♂) after gut infection with Aeromonas hydrophila.

Aeromonas hydrophila can pose a great threat to fish survival. In this study, we investigated the differential immune and redox response in gut-liver axis of hybrid fish (WR) undergoing gut infection. WR anally intubated with A. hydrophila showed severe midgut injury with decreased length-to-width ratios of villi along with GC hyperplasia and enhanced antioxidant activities, but expression profiles of cytokines, chemokines, antibacterial molecules, redox sensors and tight junction proteins decreased dramatically. In contrast, immune-related gene expressions and antioxidant activities increased significantly in liver of WR following gut infection with A. hydrophila. These results highlighted the differential immune regulation and redox balance in gut-liver axis response to bacterial infection.

Long-term Survival in Hospitalized Patients with Lung Cancer among Peasants in the Coal-producing Area in Eastern Yunnan, China / 中国肺癌杂志

BACKGROUND@#Xuanwei and Fuyuan are rural counties, located in the late Permian coal poly area of eastern Yunnan and western Guizhou, where lung cancer mortality rates are among the highest in the China, with similarity for both men and women, younger age at diagnosis and death, and higher in rural areas than in urban areas. In this paper, long-term follow-up of lung cancer cases in local peasants was conducted to observe their survival prognosis and its influencing factors.@*METHODS@#Data of patients diagnosed with lung cancer from January 2005 to June 2011, who had lived in Xuanwei and Fuyuan counties for many years, were collected from 20 hospitals at the local provincial, municipal and county levels. To estimate survival outcomes, individuals were followed up until the end of 2021. The 5-year, 10-year and 15-year survival rates were estimated using the Kaplan-Meier method. Survival differences were examined with Kaplan-Meier curves and Cox proportional hazards models.@*RESULTS@#A total of 3,017 cases were effectively followed up (2,537 peasants and 480 non-peasants). The median age at diagnosis was 57 years, and the median follow-up time was 122 months. During the follow-up period, 2,493 cases (82.6%) died. The distribution of cases by clinical stage was as follows: stage I (3.7%), stage II (6.7%), stage III (15.8%), stage IV (21.1%) and unknown stage (52.7%). Treatment at the provincial, municipal and county-level hospitals accounted for 32.5%, 22.2% and 45.3%, respectively, and surgical treatment was performed in 23.3% of cases. The median survival time was 15.4 months (95%CI: 13.9-16.1), and the 5-year, 10-year and 15-year overall survival rates were 19.5% (95%CI: 18.0%-21.1%), 7.7% (95%CI: 6.5%-8.8%) and 2.0% (95%CI: 0.8%-3.9%), respectively. Peasants with lung cancer had a lower median age at diagnosis, higher proportion residing in remote rural areas, and higher use of bituminous coal as a household fuel. They also have a lower proportion of early-stage cases, treatment at provincial or municipal hospitals, and surgical treatment, leading to poorer survival outcomes (HR=1.57). Even when considering factors such as gender, age, residential location, clinical stage at diagnosis, histological type, hospital level of service, and surgical intervention, peasants still exhibit a survival disadvantage. Multivariable Cox model analysis comparing peasants and non-peasants reveals that surgical intervention, tumor-node-metastasis (TNM) stage, and hospital level of service are common factors influencing survival prognosis, while the use of bituminous coal as a household fuel, hospital level of service and adenocarcinoma (compared to squamous cell carcinoma) are independent prognostic factors for lung cancer survival among peasants.@*CONCLUSIONS@#The lower lung cancer survival rate among peasants is associated with their lower socioeconomic status, lower proportion of early-stage diagnoses, lower proportion of surgical interventions, and treatment at provincial-level hospitals. Furthermore, the impact of other factors such as high-risk exposure to bituminous coal pollution on survival prognosis requires further investigation.

Sex-specific associations of the urinary fourteen-metal mixture with NAFLD and liver fibrosis among US adults: A nationally representative study.

Although previous studies have examined the hepatotoxicity of single metal exposure, the associations between metal mixture and non-alcoholic fatty liver disease (NAFLD) or fibrosis remain unclear. This study investigated the associations of urinary metal mixture with the risks of NAFLD and liver fibrosis in US adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017.01 to 2020.03. Vibration-controlled transient elastography was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are indicators of NAFLD and liver fibrosis respectively. Three novel mixture modeling approaches including the Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) were used to estimate the associations of the urinary fourteen-metal mixture with Ln CAP and Ln LSM. There were 2283 adults aged over 18 years (1209 women and 1074 men) were included. Among women, urinary metal mixture was positively associated with Ln CAP in the BKMR and qgcomp models (both P < 0.05). However, no significantly associations of urinary metal mixture with Ln CAP were observed among men in all models (all P > 0.05). The metal mixture was not associated with Ln LSM in the three models regardless of genders (all P > 0.05). In conclusion, we observed sex-specific associations between urinary metal mixture and the prevalence of NAFLD in US adults. These findings emphasize the role of environmental heavy metal exposure in the development of NAFLD, and confirm the need for more prospective cohort studies on sex-specific manner.

Transcriptome analysis and co-expression network reveal the mechanism linking mitochondrial function to immune regulation in red crucian carp (Carassius auratus red var) after Aeromonas hydrophila challenge.

Aeromonas hydrophila is a common pathogen of freshwater fish. In this study, A. hydrophila infection was shown to cause tissue damage, trigger physiological changes as well as alter the expression profiles of immune- and metabolic-related genes in immune tissues of red crucian carp (RCC). Transcriptome analysis revealed that acute A. hydrophila infection exerted a profound effect on mitochondrial oxidative phosphorylation linking metabolic regulation to immune response. In addition, we further identified cellular senescence, apoptosis, necrosis and mitogen-activated protein kinase signal pathways as crucial signal pathways in the kidney of RCC subjected to A. hydrophila infection. These findings may have important implications for understanding modulation of immunometabolic response to bacterial infection.

Comparative analysis on the immunoregulatory roles of ferritin M in hybrid fish (Carassius cuvieri ♀ × Carassius auratus red var ♂) and its parental species after bacterial infection.

Ferritin M is involved in the regulation of fish immunity. In this study, open reading frame (ORF) sequences of ferritin M from hybrid fish and its parental species were 534 bp. Tissue-specific analysis indicated that the highest level of ferritin M from red crucian carp was observed in kidney, while peaked expressions of ferritin M from white crucian carp and hybrid carp were observed in gill. Elevated levels of ferritin M from hybrid carp and its parental species were detected in immune-related tissues following Aeromonas hydrophila infection or in cultured fish cell lines after lipopolysaccharide (LPS) challenge. Ferritin M overexpression could attenuate NF-κB and TNFα promoter activity in their respective fish cells. Purified ferritin M fusion proteins elicited in vitro binding activity to A. hydrophila and Edwardsiella tarda, lowered bacterial dissemination to tissues and alleviated inflammatory response. Furthermore, treatment with ferritin M fusion proteins could mitigate bacteria-induced liver damage and rescue antioxidant activity. These results suggested that ferritin M in hybrid fish showed a similar immune defense against bacteria infection in comparison with those of its parental species.

Using RSM for Optimum of Optimum Production of Peptides from Edible Bird's Nest By-Product and Characterization of Its Antioxidant's Properties.

In this research, the neutrase hydrolysis conditions of edible bird's nest (EBN) by-products were optimized by response surface methodology (RSM). Antioxidant peptides were then isolated from the EBN by-products by ultrafiltration and chromatography taking the DPPH radical scavenging ability as an indicator. The antioxidant activity of the purified peptides was estimated by radical scavenging ability and sodium nitroprusside (SNP)-induced damage model in PC12 cells. When the enzyme concentration was10 kU/g-hydrolysis temperature was 45 °C, and hydrolysis time was 10.30 h, the degree of hydrolysis (DH) of EBN by-product hydrolysate (EBNH) was the highest. The purified peptide exerted strong scavenging ability with EC50 values of 0.51, 1.31, and 0.65 mg/mL for DDPH, ABTS, and O2- radicals, respectively. In addition, the purified peptides could significantly reduce the SNP-induced oxidative damage of PC12 cells, and twelve peptides that were rich in leucine (Leu), valine (Val), and lysine (Lys) were identified by LC-MS/MS. These results suggested that EBN by-products have potential as new materials for natural antioxidant peptides.

Metabolite features and oxidative response in kidney of red crucian carp (Carassius auratus red var) after Aeromonas hydrophila challenge.

Aeromonas hydrophila can threaten the survival of freshwater fish. In this study, A. hydrophila challenge could induce tissue damage, promote antioxidant imbalance as well as alter the transcript levels of oxidative stress indicators, apoptotic genes and metabolic enzyme genes in kidney of red crucian carp (RCC). Metabolomics analysis revealed that A. hydrophila challenge had a profound effect on amino acid metabolism and lipid metabolism. In addition, we further identified dipeptides, fatty acid derivatives, cortisol, choline and tetrahydrocortisone as crucial biomarkers in kidney of RCC subjected to A. hydrophila infection. These results highlighted the importance of metabolic strategy against bacterial infection.

A novel ferritin L (FerL) in hybrid crucian carp could participate in host defense against Aeromonas hydrophila infection and diminish inflammatory signals.

FerL, a multifunctional iron-storage polypeptide, not only exhibited a regulatory role in iron metabolism, but also participated in the regulation of fish immunity. In this study, ORF sequence of WR-FerL was 522 bp, encoding 173 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-FerL was detected in spleen. A. hydrophila challenge and LPS stimulation could sharply enhance WR-FerL mRNA expression in tissues and fish cells, respectively. Purified WR-FerL fusion peptide exhibited in vitro binding activity to A. hydrophila and endotoxin, limited bacterial dissemination to tissues as well as attenuated A. hydrophila-induced production of pro-inflammatory cytokines. Moreover, WR-FerL overexpression could abrogate NF-κB and TNFα promoter activity in fish cells. These results indicated that WR-FerL could play an important role in host defense against A. hydrophila infection.

Blood cell characterization and transcriptome analysis reveal distinct immune response and host resistance of different ploidy cyprinid fish following Aeromonas hydrophila infection.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

Comparative analysis of erythrocyte hemolysis, plasma parameters and metabolic features in red crucian carp (Carassius auratus red var) and triploid hybrid fish following Aeromonas hydrophila challenge.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila challenge could promote the erythrocyte hemolysis, increase free hemoglobin (FHB) level and generate malondialdehyde (MDA) production in plasma but decrease the levels of total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (ALP) and lysozyme (LZM) of red crucian carp (RCC, 2 N = 100) and triploid hybrid fish (3 N fish, 3 N = 150) following A. hydrophila challenge. Elevated expression levels of heat shock protein 90 alpha (HSP90α), matrix metalloproteinase 9 (MMP-9), free fatty acid receptor 3 (FFAR3), paraoxonase 2 (PON2) and cytosolic phospholipase A2 (cPLA2) were observed in A. hydrophila-infected fish. In addition, A. hydrophila challenge could significantly increase expressions of cortisol, leucine, isoleucine, glutamate and polyunsaturated fatty acids (PUFAs) in RCC and 3 N, while glycolysis and tricarboxylic acid cycle appeared to be inactive. We identified differential fatty acid derivatives and their metabolic networks as crucial biomarkers from metabolic profiles of different ploidy cyprinid fish subjected to A. hydrophila infection. These results highlighted the comparative metabolic strategy of different ploidy cyprinid fish against bacterial infection.

Ferritin H can counteract inflammatory response in hybrid fish and its parental species after Aeromonas hydrophila infection.

Ferritin H can participate in the regulation of fish immunity. Tissue-specific analysis revealed that the highest expressions of Ferritin H in parental species were observed in spleen, while peaked level of Ferritin H mRNA in hybrid fish was observed in liver. In addition, A. hydrophila challenge could sharply enhance their Ferritin H mRNA expression in liver, kidney and spleen. To further investigate their roles in immune regulation, their Ferritin H fusion proteins were produced in vitro. Ferritin H fusion proteins could exhibit a direct binding activity to A. hydrophila and endotoxin in a dose-dependent manner, restrict dissemination of A. hydrophila to tissues and abrogate inflammatory cascades. Moreover, treatment with Ferritin H fusion proteins could reduce A. hydrophila-induced lipid peroxidation. These results indicated that Ferritin H in hybrid fish elicited a similar immune regulation of A. hydrophila-induced inflammatory signals in comparison with those of its parents.

A novel NK-lysin in hybrid crucian carp can exhibit cytotoxic activity in fish cells and confer protection against Aeromonas hydrophila infection in comparison with Carassius cuvieri and Carassius auratus red var.

NK-lysin, an effector of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), not only exhibits cytotoxic effect in fish cells, but also participates in the immune defense against pathogenic infection. In this study, ORF sequences of RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin were 369 bp. Tissue-specific analysis revealed that the highest expressions of RCC-NK-lysin and WCC-NK-lysin were observed in gill, while the peaked level of WR-NK-lysin mRNA was observed in spleen. A. hydrophila infection sharply increased RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin mRNA expression in liver, trunk kidney and spleen. In addition, elevated levels of NK-lysin mRNA were observed in cultured fin cell lines of red crucian carp (RCC), white crucian carp (WCC) and their hybrid offspring (WR) after Lipopolysaccharide (LPS) challenge. RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin exerted regulatory roles in inducing ROS generation, modulating mitochondrial membrane potential, decreasing fish cell viability and antagonizing survival signalings, respectively. RCC/WCC/WR-NK-lysin-overexpressing fish could up-regulate expressions of inflammatory cytokines and decrease bacterial loads in spleen. These results indicated that NK-lysin in hybrid fish contained close sequence similarity to those of its parents, possessing the capacities of cytotoxicity and immune defense against bacterial infection.

Effect of Lipopolysaccharide (LPS) stimulation on apoptotic process and oxidative stress in fibroblast cell of hybrid crucian carp compared with those of Carassius cuvieri and Carassius auratus red var.

Bacterial LPS is a heat-stable endotoxin and wall components of gram negative bacteria, which can exhibit a toxicological effect on physiology and biochemical activities of fish. In this study, we investigated the effect of LPS exposure on cell viability, oxidative stress, caspase activity and immune-related gene expressions in cultured fin cell lines of red crucian carp, white crucian carp and their hybrid offspring. LPS stimulation could reduce fish cell viability, whereas gene expression levels and promoter activities in inflammatory signals increased dramatically. Moreover, enhanced levels of intracellular oxidative stress and decreased levels of mitochondrial membrane potential (MMP) were observed in LPS-induced fish cells. N-Acetyl-L-cysteine (NAC) could alleviate LPS-stimulated reactive oxygen species (ROS) generation and caspase-3 activity in fish cells. These results suggested that ROS-mediated cytotoxic stress was involved in LPS-induced inflammation and mitochondrial damage in cultured fish cells.