Antibacterial activity of bacteriophage-encoded endolysins against planktonic and biofilm cells of pathogenic Escherichia coli.

This study was designed to assess the possibility of using bacteriophage-encoded endolysins for controlling planktonic and biofilm cells. The endolysins, LysEP114 and LysEP135, were obtained from plasmid vectors containing the endolysin genes derived from Escherichia coli phages. The high identity (>96%) was observed between LysEP114 and LysEP135. LysEP114 and LysEP135 were characterized by pH, thermal, and lactic acid stability, lytic spectrum, antibacterial activity, and biofilm eradication. The molecular masses of LysEP114 and LysEP135 were 18.2 kDa, identified as muramidases. LysEP114 and LysEP135 showed high lytic activity against the outer membrane-permeabilized E. coli KCCM 40405 at below 37°C, between pH 5 to 11, and below 70 mM of lactic acid. LysEP114 and LysEP135 showed the broad rang of lytic activity against E. coli KACC 10115, S. Typhimurium KCCM 40253, S. Typhimurium CCARM 8009, tetracycline-resistant S. Typhimurium, polymyxin B-resistant S. Typhimurium, chloramphenicol-resistant S. Typhimurium, K. pneumoniae ATCC 23357, K. pneumoniae CCARM 10237, and Shigella boydii KACC 10792. LysEP114 and LysEP135 effectively reduced the numbers of planktonic E. coli KCCM by 1.7 and 2.1 log, respectively, when treated with 50 mM lactic acid. The numbers of biofilm cells were reduced from 7.3 to 4.1 log CFU/ml and 2.2 log CFU/ml, respectively, when treated with LysEP114- and LysEP135 in the presence of 50 mM lactic acid. The results suggest that the endolysins in combination with lactic acid could be potential alternative therapeutic agents for controlling planktonic and biofilm cells.

Effects of red-light irradiation and melatonininjection on the antioxidant capacity and occurrence of apoptosis in abalones (Haliotis discus hannai) subjected to thermal stress.

High ocean temperatures caused by global warming induce oxidative stress in aquatic organisms. Melatonin treatment and irradiation using red light-emitting diodes (LEDs) have been reported to reduce oxidative stress in a few aquatic organisms. However, the effects of red LED irradiation and melatonin injection on the antioxidant capacity and degree of apoptosis in abalones, which are nocturnal organisms, have not yet been reported. In this study, we compared the expression levels of antioxidant enzymes, total antioxidant capacity, and the degree of apoptosis in abalones subjected to red LED irradiation and melatonin treatment. The results revealed that at high water temperatures (25 °C), the mRNA expression levels of the superoxide dismutase (SOD) and glutathione peroxidase (GPx) genes and the antioxidant activity of SOD decreased in abalones in the red-LED irradiated and melatonin-treated groups compared with those in abalones in the control group. Although high water temperatures induced DNA damage in the abalone samples, the degree of apoptosis was lower in the red-LED irradiated and melatonin-treated groups than in the control group. Overall, the abalones in the melatonin-treated and red-LED irradiated groups showed reduced oxidative stress and increased antioxidant enzyme levels under thermal stress compared with those in the control group. Therefore, red LED irradiation is a promising alternative to melatonin treatment, which is difficult to administer continuously for a long time, for protecting abalones from oxidative stress.

The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest.

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

Organ-Specific Mitochondrial Alterations Following Ischemia-Reperfusion Injury in Post-Cardiac Arrest Syndrome: A Comprehensive Review.

BACKGROUND: Mitochondrial dysfunction, which is triggered by systemic ischemia-reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. METHODS AND RESULTS: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. CONCLUSIONS: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury.

Investigating ischemia and reperfusion-induced organ damage in severe cardiac arrest: A comprehensive proteomics perspective.

Image 1.

Melatonin injection and red light irradiation affect the antioxidant response and cell damage in disk abalone (Haliotis discus hannai) exposed to high water temperatures.

The effects of red light-emitting diode (LED) light irradiation (630 nm, 0.5 W/m2) and melatonin (10-8 and 10-7 M) on oxidative stress and physiological responses in abalones exposed to high temperatures (28°C) were investigated. Changes in messenger RNA (mRNA) expressions of melatonin receptor (MT-R), heat shock protein 70 (HSP70), and antioxidant enzymes, as well as alterations in H2O2 levels in the hemolymph, were examined. The results revealed that high-temperature-stressed abalones treated with melatonin injections or exposed to red LED light showed a significant increase in MT-R mRNA expression, while HSP70 mRNA expression decreased. Notably, HSP70 mRNA expression levels in the red LED light-irradiated group were similar to those in the group injected with 10-8 M melatonin after 24 h exposure. Abalones treated with melatonin at 20°C or irradiated with red LED light exhibited decreased H2O2 levels and reduced antioxidant enzyme mRNA expression compared with those of the control group. However, the high-temperature environment induced oxidative stress in abalones, leading to increased antioxidant enzyme mRNA expression compared with that under 20°C conditions. Moreover, abalones exposed to high-temperature stress exhibited hepatopancreatic DNA damage, which was attenuated by melatonin treatment or red LED light irradiation. Hence, red LED light reduces oxidative stress, boosts antioxidant enzymes, and alleviates DNA damage in high-temperature-stressed abalones, akin to 10-8 M melatonin treatment. Therefore, considering the practical challenges of continuous melatonin administration to abalones, utilizing red LED light emerges as a practical, effective alternative to protect abalones from oxidative stress compared to 10-8 M melatonin treatment.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Exposure to bisphenol A and fiber-type microplastics induce oxidative stress and cell damage in disk abalone Haliotis discus hannai: Bioaccumulation and toxicity.

Along with environmental pollution caused by rapid economic development and industrialization, plastic waste is emerging as a global concern in relation to marine ecosystems and human health. Among the microplastics, fiber-type microfibers (MF) and bisphenol A (BPA), which are widely used as plasticizers, do not decompose well in the ocean, and tend to accumulate in organisms, generating an increased oxidative stress response. This study investigated the abalones' antioxidant and cell death responses following exposure to the environmental pollutants MF and BPA. Levels of malondialdehyde (MDA) and DNA damage increased over time, demonstrating the degree of lipid peroxidation and DNA damage in abalones exposed to individual and combined environmental conditions of MF and BPA. Compared to the single MF and BPA exposure groups, the combined exposure group showed a higher expression of antioxidant enzymes. A similar pattern was seen in the expression of the apoptosis enzyme caspase-3. Both MF and BPA caused oxidative stress and antioxidant enzymes were expressed to alleviate it, but it is believed that cell damage occurred because the stress level exceeded the allowed range.

Toxic effects of polystyrene microbeads and benzo[α]pyrene on bioaccumulation, antioxidant response, and cell damage in goldfish Carassius auratus.

Microplastics (MP) are harmful, causing stress in aquatic species and acting as carriers of hydrophobicity. In aquatic environments, benzo[α]pyrene (BaP) is an endocrine-disrupting chemical that accumulates in the body and causes toxic reactions in living organisms. We investigated the effects of single and combined microbead (MB) and BaP environments on goldfish antioxidant response and apoptosis. For 120 h, goldfish were exposed to single (MB10, MB100, and BaP5) and combined (MB10+BaP5 and MB100+BaP5) environments of 10 and 100 beads/L of 0.2 µm polystyrene MB and 5 µg/L BaP. We measured MB and BaP bioaccumulation as well as plasma parameters including ALT, AST, and glucose. The level of oxidative stress was determined by evaluating lipid peroxidation (LPO) and total antioxidant capacity (TAC) in plasma, as well as antioxidant-related genes for superoxide dismutase and catalase (SOD and CAT) and caspase-3 (Casp3) mRNA expression in liver tissue. The TUNEL assay was used to examine SOD in situ hybridization and apoptosis in goldfish livers. Except for the control group, plasma LPO levels increased at the end of the exposure period in all experimental groups. TAC increased up to 24 h of exposure and then maintained a similar level until the trial ended. SOD, CAT, and Casp3 mRNA expression increased substantially up to 120 h as the exposure concentration and time increased. The TUNEL assay revealed more signals and apoptotic signals in the combined exposure environments as a consequence of SOD in situ hybridization than in single exposure environments. These results suggest that combined exposure to toxic substances causes oxidative stress in organisms, which leads to apoptosis.

Neurological Improvement via Lysophosphatidic Acid Administration in a Rodent Model of Cardiac Arrest-Induced Brain Injury.

Lysophosphatidic acid (LPA) serves as a fundamental constituent of phospholipids. While prior studies have shown detrimental effects of LPA in a range of pathological conditions, including brain ischemia, no studies have explored the impact of LPA in the context of cardiac arrest (CA). The aim of this study is to evaluate the effects of the intravenous administration of an LPA species containing oleic acid, LPA (18:1) on the neurological function of rats (male, Sprague Dawley) following 8 min of asphyxial CA. Baseline characteristics, including body weight, surgical procedure time, and vital signs before cardiac arrest, were similar between LPA (18:1)-treated (n = 10) and vehicle-treated (n = 10) groups. There was no statistically significant difference in 24 h survival between the two groups. However, LPA (18:1)-treated rats exhibited significantly improved neurological function at 24 h examination (LPA (18:1), 85.4% ± 3.1 vs. vehicle, 74.0% ± 3.3, p = 0.045). This difference was most apparent in the retention of coordination ability in the LPA (18:1) group (LPA (18:1), 71.9% ± 7.4 vs. vehicle, 25.0% ± 9.1, p < 0.001). Overall, LPA (18:1) administration in post-cardiac arrest rats significantly improved neurological function, especially coordination ability at 24 h after cardiac arrest. LPA (18:1) has the potential to serve as a novel therapeutic in cardiac arrest.

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

Degradation of phenol by perborate in the presence of iron-bearing and carbonaceous materials.

We investigated the oxidation of phenol by perborate-a newly proposed oxidant-in the presence of iron-bearing and carbonaceous materials through batch experiments. We hypothesized that the oxidation of phenol by perborate was enhanced due to the formation of reactive oxygen species (ROS) in the presence of iron-bearing or carbonaceous materials. Zero-valent iron and ferrous iron (Fe2+) promoted the oxidation of phenol by perborate. Biochar, granular activated carbon, an anode carbonaceous material recovered from a spent Li-ion battery, and graphite also accelerated the oxidation of phenol by perborate. Quenching experiments with radical scavengers and electron paramagnetic resonance (EPR) analysis revealed that hydroxyl (˙OH) and superoxide (O2˙-) radicals were generated and enhanced the degradation of phenol in the perborate systems. Singlet oxygen (1O2) was involved in the iron-bearing material-perborate systems. Moreover, we found that Persil®, a commercial perborate detergent, enhances the oxidation of phenol in the presence of iron-bearing and carbonaceous materials. Our results suggest that perborate can be used for advanced oxidation processes to remediate recalcitrant organic contaminants in natural environments and engineered systems.

Combined antimicrobial effect of phage-derived endolysin and depolymerase against biofilm-forming Salmonella Typhimurium.

This study was designed to evaluate the antimicrobial activity of phage-derived endolysin (LysPB32) and depolymerase (DpolP22) against planktonic and biofilm cells of Salmonella Typhimurium (STKCCM). Compared to the control, the numbers of STKCCM were reduced by 4.3 and 5.9 log, respectively, at LysPB32 and LysPB32 + DpolP22 in the presence of polymyxin B (PMB) after 48-h incubation at 37 °C. LysPB32 + DpolP22 decreased the relative fitness (0.8) and the cross-resistance of STKCCM to chloramphenicol (CHL), cephalothin (CEP), ciprofloxacin (CIP), and tetracycline (TET) in the presence of PMB. The MICtrt/MICcon ratios of CHL, CEP, CIP, PMB, and TET were between 0.25 and 0.50 for LysPB32 + DpolP22 in the presence of PMB. These results suggest that the application of phage-encoded enzymes with antibiotics can be a promising approach for controlling biofilm formation on medical and food-processing equipment. This is noteworthy in that the application of LysPB32 + DpolP22 could increase antibiotic susceptibility and decrease cross-resistance to other antibiotics.

Microplastic polyamide toxicity: Neurotoxicity, stress indicators and immune responses in crucian carp, Carassius carassius.

This study aimed to determine the toxicity standard and potential risks and effects of polyamide (PA) exposure on neurotoxicity, stress indicators, and immune responses in juvenile crucian carp Carassius carassius. Numerous microplastics (MPs) exists within aquatic environments, leading to diverse detrimental impacts on aquatic organisms. The C. carassius (mean weight, 23.7 ± 1.6 g; mean length, 13.9 ± 1.4 cm) were exposed to PA concentrations of 0, 4, 8, 16, 32 and 64 mg/L for 2 weeks. Among the neurotransmitters, the acetylcholinesterase (AChE) activity in the liver, gill, and intestine of C. carassius was significantly inhibited by PA exposure. Stress indicators such as cortisol and heat shock protein 70 (HSP70) in the liver, gill, and intestine of C. carassius were significantly increased, while immune responses to lysozyme and immunoglobulin M (IgM) were significantly decreased. Our study demonstrates the toxic effects of MP exposure on crucian carp's neurotoxicity, stress indicators, and immune responses.

Effects of microfiber and bead microplastic exposure in the goldfish Carassius auratus: Bioaccumulation, antioxidant responses, and cell damage.

We confirmed antioxidant-related gene expression, bioaccumulation, and cell damage following exposure to various microplastics in vivo and in vitro in the goldfish Carassius auratus. Exposure of C. auratus to a 500 µm fiber-type microplastic environment (MF; 10 and 100 fibers/L) and two sizes (0.2 and 1.0 µm) of beads (MB; 10 and 100 beads/L) for 120 h increased superoxide dismutase (SOD) mRNA expression in the liver until 24 h followed by a decrease. Whereas, catalase (CAT) mRNA expression increased from 12 h to the end of the in vivo experiment. In vitro experiments were conducted with diluted microfibers (1 and 5 fibers/L) and microbeads (1 and 5 beads/L) using cultured liver cells. The results of SOD and CAT mRNA expression analysis conducted in vitro showed a tendency similar to those of experiments conducted in vivo. The H2O2 level increased in the high-concentration experimental groups compared with that in the low-concentration groups of 0.2-µm beads. In addition, the H2O2 level increased in both MF and MB groups from 12 h of exposure. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma were used as indicators of liver damage in fish. The ALT and AST levels increased up to 120 h after exposure. Caspase-3 (casp-3) mRNA expression was higher in the MB group than in the MF group. We visually confirmed liver casp-3 mRNA signals using in situ hybridization. The degree of DNA damage in the MF and MB high-concentration groups increased with the exposure time. The tail length and percent of DNA in the tail of the MB group were significantly higher than those of the MF group, confirming that DNA damage was greater in the MB group. Both fiber- and bead-type microplastics induced oxidative stress in C. auratus, but the bead-type induced greater stress than the fiber-type.

Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Review of cadmium toxicity effects on fish: Oxidative stress and immune responses.

Cadmium (Cd) in aquatic environments can cause environmental toxicity to fish and induce oxidative stress owing to an excessive production of reactive oxygen species in fish bodies. Fish have developed various antioxidant systems to protect themselves from reactive oxygen species; thus, a change in antioxidant responses in fish can be a criterion for evaluating oxidative stress resulting from Cd exposure. Because Cd exposure may be recognized as an exogenous substance by a fish body, it may lead to the stimulation or suppression of its immune system. Various immune responses can be assessed to evaluate Cd toxicity in fish. This review aimed to identify the impacts of Cd exposure on oxidative stress and immunotoxicity in fish as well as identify accurate indicators of Cd toxicity in aquatic ecosystems.