Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton-Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment.

The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.

In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.

Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.

Alterations in cell viability, reactive oxygen species production, and modulation of gene expression involved in mitogen-activated protein kinase/extracellular regulating kinase signaling pathway by glyphosate and its commercial formulation in hepatocellular carcinoma cells.

Glyphosate (N-phosphonomethyl glycine) is a non-selective, organophosphate herbicide widely used in agriculture and forestry. We investigated the possible toxic effects of the glyphosate active compound and its commercial formulation (Roundup Star®) in the human hepatocellular carcinoma (HepG2) cell line, including their effects on the cytotoxicity, cell proliferation, reactive oxygen species (ROS) levels, and expression of oxidative stress-related genes such as HO-1, Hsp70 Nrf2, L-FABP, and Keap1. MTT and NRU tests indicated that the IC50 values of Roundup Star® were 219 and 140 µM, respectively, and because glyphosate failed to induce cell death at the studied concentrations, an IC50 value could not be determined for this cell line. Roundup Star at concentrations of 50 and 100 µM significantly increased (39.58% and 52%, respectively) cell proliferation, which 200 µM of glyphosate increased by 35.38%. ROS levels increased by 27.97% and 44.77% for 25 and 100 µM of Roundup Star and 32.74% and 38.63% for 100 and 200 µM of glyphosate exposure. In conclusion, Roundup Star and glyphosate significantly increased expression levels of selected genes related to the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. This suggests that ROS production and the MAPK/ERK signaling pathway may be key molecular mechanisms in the toxicity of glyphosate in liver cells.

Dalbavancin Boosts the Ability of Neutrophils to Fight Methicillin-Resistant Staphylococcus aureus.

Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils.

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models.

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: (1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; (2) the biological effect was influenced by the nature of the central azole ring of the ligands-1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; (3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin's lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.

Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production.

Ruthenium complexes are developed as substitutes for platinum complexes to be used in the chemotherapy of hematological and gynecological malignancies, such as ovarian cancer. We synthesized and screened 14 ruthenium half-sandwich complexes with bidentate monosaccharide ligands in ovarian cancer cell models. Four complexes were cytostatic, but not cytotoxic on A2780 and ID8 cells. The IC50 values were in the low micromolar range (the best being 0.87 µM) and were similar to or lower than those of the clinically available platinum complexes. The active complexes were cytostatic in cell models of glioblastoma, breast cancer, and pancreatic adenocarcinoma, while they were not cytostatic on non-transformed human skin fibroblasts. The bioactive ruthenium complexes showed cooperative binding to yet unidentified cellular target(s), and their activity was dependent on reactive oxygen species production. Large hydrophobic protective groups on the hydroxyl groups of the sugar moiety were needed for biological activity. The cytostatic activity of the ruthenium complexes was dependent on reactive species production. Rucaparib, a PARP inhibitor, potentiated the effects of ruthenium complexes.

Fengycins, Cyclic Lipopeptides from Marine Bacillus subtilis Strains, Kill the Plant-Pathogenic Fungus Magnaporthe grisea by Inducing Reactive Oxygen Species Production and Chromatin Condensation.

Rice blast caused by the phytopathogen Magnaporthe grisea poses a serious threat to global food security and is difficult to control. Bacillus species have been extensively explored for the biological control of many fungal diseases. In the present study, the marine bacterium Bacillus subtilis BS155 showed a strong antifungal activity against M. grisea The active metabolites were isolated and identified as cyclic lipopeptides (CLPs) of the fengycin family, named fengycin BS155, by the combination of high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS). Analyses using scanning and transmission electron microscopy revealed that fengycin BS155 caused morphological changes in the plasma membrane and cell wall of M. grisea hyphae. Using comparative proteomic and biochemical assays, fengycin BS155 was demonstrated to reduce the mitochondrial membrane potential (MMP), induce bursts of reactive oxygen species (ROS), and downregulate the expression level of ROS-scavenging enzymes. Simultaneously, fengycin BS155 caused chromatin condensation in fungal hyphal cells, which led to the upregulation of DNA repair-related protein expression and the cleavage of poly(ADP-ribose) polymerase (PARP). Altogether, our results indicate that fengycin BS155 acts by inducing membrane damage and dysfunction of organelles, disrupting MMP, oxidative stress, and chromatin condensation, resulting in M. grisea hyphal cell death. Therefore, fengycin BS155 and its parent bacterium are very promising candidates for the biological control of M. grisea and the associated rice blast and should be further investigated as such.IMPORTANCE Rice (Oryza sativa L.) is the most important crop and a primary food source for more than half of the world's population. Notably, scientists in China have developed several types of rice that can be grown in seawater, avoiding the use of precious freshwater resources and potentially creating enough food for 200 million people. The plant-affecting fungus Magnaporthe grisea is the causal agent of rice blast disease, and biological rather than chemical control of this threatening disease is highly desirable. In this work, we discovered fengycin BS155, a cyclic lipopeptide material produced by the marine bacterium Bacillus subtilis BS155, which showed strong activity against M. grisea Our results elucidate the mechanism of fengycin BS155-mediated M. grisea growth inhibition and highlight the potential of B. subtilis BS155 as a biocontrol agent against M. grisea in rice cultivation under both fresh- and saltwater conditions.

Effect of freezing bull semen in two non-egg yolk extenders on post-thaw sperm quality.

Traditionally, extenders for bull semen included egg yolk or milk, but recently there has been a move to avoid material of animal origin. The aim of this study was to evaluate the effects of two commercial extenders (based on soya lecithin and liposomes) on bull sperm quality after cryopreservation. Post-thaw sperm quality was evaluated by computer-assisted sperm analysis and flow cytometric assessment of membrane integrity, chromatin integrity, mitochondrial membrane potential, production of reactive oxygen species and tyrosine phosphorylation. Furthermore, an artificial insemination (AI) trial was conducted, and 56-day non-return rates were evaluated. Semen frozen in the liposome-based extender showed similar membrane integrity and higher mitochondrial membrane potential compared to those in the soya lecithin-based extender. Chromatin integrity and production of live H2 O2 + reactive oxygen species were similar in both extenders. Less superoxide was produced in the samples extended with liposome-based extender, with or without menadione stimulation. Chromatin integrity and tyrosine phosphorylation were not affected by either type of extender. No differences in 56-day non-return rate between extenders containing soya lecithin and liposomes were observed in the AI trial (66% ± 0.8 and 65% ± 0.8, respectively). In conclusion, the sperm quality of bull semen frozen in the two extenders that do not contain material of animal origin was similar, although the semen frozen in the liposome-based extender had higher mitochondrial membrane potential. Either extender could be used in situations where extenders containing material of animal origin are to be avoided.

Vitamin E-Coated Dialyzer Inhibits Oxidative Stress.

AIM: To examine the effects of vitamin E-coated dialyzer on oxidative stress in vitro. METHODS: A dialyzer with a synthetic polymer membrane (APS-11SA) and vitamin E-coated dialyzer (VPS-11SA) were connected to a blood tubing line, and U937 cells were circulated in the device. The circulating fluid was collected at 1, 2, 5, 10, 25, and 50 cycles, which are estimated numbers of passes through the dialyzer. Intracellular reactive oxygen species (ROS) production, malondialdehyde (MDA), and Cu/Zn-superoxide dismutase (SOD) were quantified. RESULTS: Intracellular ROS production was increased in the first cycle by APS-11SA and was decreased throughout the experiment by VPS-11SA. Intracellular ROS production in the VPS-11SA device was lower, and MDA levels were decreased. MDA levels were lower during VPS-11SA processing than during APS-11SA processing. Cu/Zn-SOD levels remained unchanged. CONCLUSION: Our results highlight anti-oxidative-stress effects of a vitamin E-coated dialyzer.

Effects of single layer centrifugation (SLC) on bull spermatozoa prior to freezing on post-thaw semen characteristics.

Single layer centrifugation (SLC) has been shown to select the most robust spermatozoa from the ejaculate in several species. Here the effects of SLC prior to freezing on various parameters of frozen-thawed bovine sperm quality are reported. Semen from 8 bulls was layered on top of a species-specific colloid, Bovicoll. After centrifugation for 20 min at 300 g, the resulting sperm pellet was resuspended in OPTIXcell® (IMV Technologies, l'Aigle, France); the SLC-selected sperm samples and uncentrifuged controls were frozen. On thawing, all sperm samples were analysed for membrane integrity, production of reactive oxygen species, mitochondrial membrane potential (MMP) and chromatin integrity. The SLC-treated samples had a higher percentage of live, superoxide-positive spermatozoa than uncentrifuged samples (27.9 ± 5.1% versus 21.7 ± 6.7%; p = .03). They had a higher proportion of spermatozoa with high mitochondrial membrane potential than uncentrifuged samples (55.9 ± 8.2% versus 40.5 ± 15.1%; p = .03) and also a lower proportion of spermatozoa with low mitochondrial membrane potential than non-treated samples (42.0 ± 8.5% versus 55.9 ± 14.4%; p = .04). No significant effects of treatment were found for membrane integrity or chromatin integrity. The effect of bull was significant on the proportions of dead, superoxide-positive spermatozoa and live, hydrogen peroxide-negative spermatozoa, as well as on membrane integrity, but it was not significant for mitochondrial membrane potential or chromatin integrity. These results suggest that SLC selects the most metabolically active bull spermatozoa from the rest of the population in normal ejaculates; the pattern of reactive oxygen species production may be different in SLC-selected spermatozoa compared to unselected samples.

Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart.

As ~80% of diabetic patients die from heart failure, an understanding of diabetic cardiomyopathy is crucial. Mitochondria occupy 35-40% of the mammalian cardiomyocyte volume and supply 95% of the heart's ATP, and diabetic heart mitochondria show impaired structure, arrangement, and function. We predict that bioenergetic inefficiencies are present in diabetic heart mitochondria; therefore, we explored mitochondrial proton and electron handling by linking oxygen flux to steady-state ATP synthesis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (ΔΨ) within rat heart tissues. Sprague-Dawley rats were injected with streptozotocin (STZ, 55 mg/kg) to induce type 1 diabetes or an equivalent volume of saline (control, n = 12) and fed standard rat chow for 8 wk. By coupling high-resolution respirometers with purpose-built fluorometers, we followed Magnesium Green (ATP synthesis), Amplex UltraRed (ROS production), and safranin-O (ΔΨ). Relative to control rats, the mass-specific respiration of STZ-diabetic hearts was depressed in oxidative phosphorylation (OXPHOS) states. Steady-state ATP synthesis capacity was almost one-third lower in STZ-diabetic heart, which, relative to oxygen flux, equates to an estimated 12% depression in OXPHOS efficiency. However, with anoxic transition, STZ-diabetic and control heart tissues showed similar ATP hydrolysis capacities through reversal of the F1F0-ATP synthase. STZ-diabetic cardiac mitochondria also produced more net ROS relative to oxygen flux (ROS/O) in OXPHOS. While ΔΨ did not differ between groups, the time to develop ΔΨ with the onset of OXPHOS was protracted in STZ-diabetic mitochondria. ROS/O is higher in lifelike OXPHOS states, and potential delays in the time to develop ΔΨ may delay ATP synthesis with interbeat fluctuations in ADP concentrations. Whereas diabetic cardiac mitochondria produce less ATP in normoxia, they consume as much ATP in anoxic infarct-like states.

Multiscale measurement of cardiac energetics.

Herein we describe our laboratories' experimental methods for interrogating cardiac energetics at the organ (whole heart), tissue (trabecula) and perforated fibre (mitochondrial) levels. In whole heart and trabecula experiments, we focus on measuring pressure-volume (force-length) work and oxygen consumption (heat production) from which mechanical efficiency is derived. In both preparations (i.e. across scales differing by three orders of magnitude) we find efficiency values of 10%-15%. Mitochondrial experiments invoke a trio of titration protocols to yield information on oxygen consumption, ATP flux, membrane potential, electron leak and reactive oxygen species production, the latter two of which index energy transfer inefficiencies.

Triadimenol promotes the production of reactive oxygen species and apoptosis with cardiotoxicity and developmental abnormalities in zebrafish.

Various types of fungicides, especially triazole fungicides, are used to prevent fungal diseases on farmlands. However, the developmental toxicity of one of the triazole fungicides, triadimenol, remains unclear. Therefore, we used the zebrafish animal model, a representative toxicological model, to investigate it. Triadimenol induced morphological alterations in the eyes and body length along with yolk sac and heart edema. It also stimulated the production of reactive oxygen species and expression of inflammation-related genes and caused apoptosis in the anterior regions of zebrafish, especially in the heart. The phosphorylation levels of Akt, ERK, JNK, and p38 proteins involved in the PI3K and MAPK pathways, which are important for the development process, were also reduced by triadimenol. These changes led to malformation of the heart and vascular structures, as observed in the flk1:eGFP transgenic zebrafish models and a reduction in the heart rate. In addition, the expression of genes associated with cardiac and vascular development was also reduced. Therefore, we elucidated the mechanisms associated with triadimenol toxicity that leads to various abnormalities and developmental toxicity in zebrafish.

The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases.

Periodontitis is a chronic oral inflammatory disease that is caused by dental plaque pathogens. Periodontal disease development and evolution are based on the host immune system, humoral and cellular immunity, the integrity of the tissues, and certain endocrine and nutritional factors. Mitochondria are significantly involved in periodontal infections and inflammation, which play a role in the inflammatory response in a variety of ways. In general, oxidative stress causes a stressful environment that subsequently leads to tissue damage and chronic inflammation. Several mutations and alterations in mitochondrial DNA lead the disease to an aggressive condition, by causing dysregulated mitochondrial function. Such mutations are significantly associated with various diseases. Numerous studies indicate chronic periodontitis patients have a decreased level of mitochondrial membrane potential, as well as adenosine triphosphate, and an increased level of reactive oxygen species production, which causes cell death in the periodontium and affects tissue growth. Further studies into the association between mitochondria and periodontitis might be helpful for the treatment and prevention of the diseases.

Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study.

Xanthine oxidoreductase (XOR) and its products contribute to the development of chronic inflammation and oxidative stress. Excessive XOR activity is believed to promote inflammatory responses and atherosclerotic plaque formation, which are major cardiovascular risk factors. The mechanisms of XOR activity in the development and progression of cardiovascular disease (CVD), coupled with the complexity of the relationship between XOR activity and the biological effects of uric acid; reactive oxygen species; and nitric oxide, which are the major products of XOR activity, have long been debated, but have not yet been clearly elucidated. Recently, a system for measuring highly sensitive XOR activity in human plasma was established, and there has been progress in the research on the mechanisms of XOR activity. In addition, there are accumulating findings about the relationship between XOR activity and CVD. In this narrative review, we summarize existing knowledge regarding plasma XOR activity and its relationship with CVD and discuss future perspectives.

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.

The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC50 value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC50 value of the complexes. The complexes containing [(η6-p-cymene)Ru(II)], [(η6-p-cymene)Os(II)] or [(η5-Cp*)Ir(III)] were biologically active unlike the complex containing [(η5-Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC50 values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positive Enterococcus and Staphylococcus aureus isolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.

Effect of dimethyl alpha-ketoglutarate supplementation on the in vitro developmental competences of ovine oocytes.

The supplementation of dimethyl alpha-ketoglutarate (DMKG) during the in vitro maturation (IVM) process has been shown to improve the in vitro developmental competences of porcine oocytes. Here, the effects of DMKG supplementation in IVM medium on the development competencies of ovine oocytes were investigated by analyzing the nuclear maturation rate to metaphase II (MII) stage, ATP synthesis, cortical granules (CGs) dynamic, F-actin polymerization, mitochondrial activity, mitochondrial damage, reactive oxygen species (ROS) production, intracellular glutathione (GSH) production, DNA damage, cellular apoptosis, fertilization capacity and blastocyst development potential of ovine oocytes. In addition, the oxidative stress damage model induced by H2O2 treatment was applied to confirm the antioxidative effect of DMKG supplementation on the development of ovine oocytes. The results showed that compared with MII oocytes without DMKG supplementation (Control group), 3 mM DMKG supplementation during IVM significantly (P < 0.05) increased nuclear maturation rate, ATP synthesis, CGs dynamic, F-actin polymerization, mitochondrial activity, GSH production and embryonic developmental competence and decreased ROS production, mitochondrial damage, DNA damage and cellular apoptosis level of ovine MII oocytes. Moreover, the reductions in the developmental competences of ovine MII oocytes caused by H2O2 induced oxidative stress damages were effectively ameliorated by the co-supplementation in IVM of 3 mM DMKG (P < 0.05). Our results demonstrate the promising effect of DMKG supplementation on the in vitro developmental competence of ovine oocytes via the reduction of oxidative stress damages and indicates further research into the clinical applications of DMKG and the development of ovine breeding technologies is warranted.

Beneficial Effect of Selenium Doped Carbon Quantum Dots Supplementation on the in vitro Development Competence of Ovine Oocytes.

Background: After the synthesis of selenium doped carbon quantum dots (Se/CDs) via a step-by-step hydrothermal synthesis method with diphenyl diselenide (DPDSe) as precursor, the beneficial effects of Se/CDs' supplementation on the in vitro development competence of ovine oocytes were firstly investigated in this study by the assay of maturation rate, cortical granules' (CGs) dynamics, mitochondrial activity, reactive oxygen species (ROS) production, epigenetic modification, transcript profile, and embryonic development competence. Results: The results showed that the Se/CDs' supplementation during the in vitro maturation (IVM) process not only enhanced the maturation rate, CGs' dynamics, mitochondrial activity and embryonic developmental competence of ovine oocytes, but remarkably decreased the ROS production level of ovine oocytes. In addition, the expression levels of H3K9me3 and H3K27me3 in the ovine oocytes were significantly up-regulated after the Se/CDs' supplementation, in consistent with the expression levels of 5mC and 5hmC. Moreover, 2994 up-regulated differentially expressed genes (DEGs) and 846 repressed DEGs were found in the oocytes after the Se/CDs' supplementation. According to the analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), these DEGs induced by the Se/CDs' supplementation were positively related to the progesterone mediated oocyte maturation and mitochondrial functions. And these remarkably up-regulated expression levels of DEGs related to oocyte maturation, mitochondrial function, and epigenetic modification induced by the Se/CDs' supplementation further confirmed the beneficial effect of Se/CDs' supplementation on the in vitro development competence of ovine oocytes. Conclusion: The Se/CDs prepared in our study significantly promoted the in vitro development competence of ovine oocytes, benefiting the extended research about the potential applications of Se/CDs in mammalian breeding technologies.

Parkinson's disease protein 7 protected against oxidative stress of myocardial infarction direct through p47phox and nicotinamide adenine dinucleotide phosphate oxidase 4.

In the present study, we aimed to investigate the role and mechanism of Parkinson's disease protein 7 (Park7) in myocardial infarction (MI). The Park7 expression in the serum and tissues was down-regulated in mice with MI. Recombinant Park7 protein protected against MI-induced injury and reduced oxidative stress in mice model. Conversely, knockout Park7 increased injury of MI and promoted oxidative stress in MI mice model. In embryonic rat cardiac myoblasts H9c2 cells, over-expression of Park7 reduced reactive oxygen species (ROS)-induced oxidative stress, while down-regulation of Park7 increased ROS-induced oxidative stress. Park7 combined nicotinamide adenine dinucleotide phosphate (NADPH) oxidase cytoplasmic subunit p47phox protein had direct effect on inducing NADPH activator. The inhibition of p47phox reduced the effects of Park7 in ROS production of H2O2-treated H9c2 cells. The regulation of NADPH participated in the effects of Park7 on ROS production of in both MI mice model and H2O2-treated H9c2 cells. Our data demonstrated that Park7 protects against oxidative stress in MI model direct through p47phox and NADPH oxidase 4.

Tritiated Water Exposure in Zebrafish (Danio rerio): Effects on the Early-Life Stages.

Tritium, a radioactive isotope of hydrogen of natural and anthropogenic origin, is ubiquitously present in the environment. Effluents of nuclear centers of production are significant anthropogenic sources. With the upcoming project of thermonuclear fusion, tritium releases in the environment may increase. It is therefore important to characterize the ecological risk linked to tritium. The effects of tritiated water (HTO) were therefore studied in zebrafish larvae exposed for 10 d to different dose rates, 1.1 × 102 , 4.1 × 102 , and 3.8 × 103 µGy/h for larvae corresponding, respectively, to a water contamination of 104 , 105 , and 106 Bq/mL of HTO. Those dose rates were higher than 10 µGy/h, which is the threshold recommended to start monitoring ecosystems where radiological contaminants are present. Mortality, embryo-larval development, immune toxicity, genotoxicity, neurotoxicity, and alterations of tissues were investigated. The results showed that HTO exposure induced DNA damage and reactive oxygen species production and modulated the expression of genes involved in detoxification processes. Moreover, modifications of the muscular tissues (degradation of myofibrils at 4 d post fertilization and disorganization of mitochondria at later stages) were observed. The results differed with HTO dose rates and with developmental stages. These results will drive future research for the development of new HTO-sensitive biomarkers and will allow us to progress in the characterization of the modes of action of tritium in fish. Environ Toxicol Chem 2020;39:648-658. © 2019 SETAC.