Increased Cell Damage Research Articles

Electrochemically Coupled Anaerobic Membrane Bioreactor Facilitates Remediation of Microplastic-Containing Wastewater

Ubiquitous microplastics (MPs) severely affect the efficiency of anaerobic membrane bioreactors (AMBR) for wastewater treatment and energy recovery by inhibiting the metabolic activity of anaerobic microorganisms. The electrochemical system can not only accelerate waste metabolism but also improve microbial resistance by promoting interspecies electron transfer within the system, which has broad application potential in the remediation of MPs wastewater. This paper attempts to evaluate the effect of electrical stimulation on the efficiency of biological wastewater treatment processes containing MPs employing an electrochemical system coupled to an anaerobic membrane bioreactor (ECAMBR). The results showed that although MP exposure inhibited methanogenic performance, electrical stimulation effectively alleviated this inhibitory effect. Further analysis showed that microplastics increased cell damage and affected enzyme activity, but electrical stimulation could affect the stress response of microorganisms, leading to changes in their cell viability and enzyme activities. The 16S-rRNA sequencing indicated that the highest abundance of hydrolytic–acidogenic bacteria Firmicutes and Bacteroidota was found at the phylum level, whereas at the genus level, it was Christensenellaceae_R-7_group, and methanogens were dominated by Methylomonas, Methyloversatilis, and Methylobacter. Functional prediction analysis indicated that carbohydrate metabolism, amino acid metabolism, and energy metabolism were the dominant metabolic pathways and that electrical stimulation could enhance their activities. This study demonstrated the important role of electrochemical stimulation in the remediation of wastewater containing high concentrations of MPs.

DNA damage and cell death in human oral squamous cell carcinoma cells: The potential biological effects of cannabidiol

ObjectiveThe present study examined the in vitro effects on oral squamous cell carcinoma cells (HSC-3) of cannabidiol (CBD), the main chemical component of Cannabis, proposed as a novel adjuvant therapy in the treatment of cancers. DesignCell viability (MTT assay), morphology (SEM), apoptosis and cell cycle (flow cytometry), and DNA damage (phospho-γ-H2AX immunofluorescence) were evaluated. Cytotoxicity was evaluated with concentrations between 100 µM and 1 µM, and two concentrations were selected for subsequent analysis: 25 µM, as toxic dose, and 6.25 µM, as non-toxic. ResultsCBD caused a dose- and time-dependent reduction in viability of 64 %, 96 %, and 99 % with 25 µM, 50 µM and 100 µM, respectively, after 72 h (p < 0.001), cell cycle arrest in G0-G1 phase with increased apoptosis in particular at 72 h for 25 µM (p < 0.001), significant morphological alterations with 25 µM, still present even at 6.25 µM, and significantly increased cell damage considering a significant increase in the percentage of highly positive cells (5 phosphorylated γH2AX foci), which is around 29 % for 25 µM and 19 % for 6.25 µM after 24 h. ConclusionsCBD inhibits oral cancer growth causing DNA damage. In general, induced cell cytotoxicity appears to be dose- and time-related. Doses of CBD ≥25 μM showed a high reduction in viability. CBD could possibly represent a new therapeutic molecule for its cytotoxic effects against oral squamous cell carcinoma. The mechanism involved in the suppressive effect caused by CBD needs further investigation.

Exosome miR-4738-3p-mediated regulation of COL1A2 through the NF-κB and inflammation signaling pathway alleviates osteoarthritis low-grade inflammation symptoms.

This study aimed to elucidate the roles of microRNA (miR)-4738-3p and the collagen type I alpha 2 chain (COL1A2) gene in the pathogenesis of osteoarthritis (OA) through bioinformatics analysis and cellular assays. The GSE55235 dataset was analyzed using the weighted gene co-expression network analysis (WGCNA) method to identify gene modules associated with OA. Key overlapping genes were identified from these modules and the GSE55235-differential expressed genes (DEGs). The expression levels of selected genes were determined in C28/I2 cells using the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-4738-3p and COL1A2 was examined in the context of interleukin 1 beta (IL-1β) induction. Exosome characterization was achieved through transmission electron microscopy (TEM), western blotting (WB), and other analyses. The study also investigated the functional relevance of miR-4738-3p in OA pathology through various molecular and cellular assays. Our findings revealed that the green module exhibited a strong correlation with the OA phenotype in the GSE55235 dataset, with COL1A2 emerging as a hub gene and miR-4738-3p as its key downstream target. IL-1β induction suggested that COL1A2 is involved in inflammation and apoptosis, while miR-4738-3p appeared to play an antagonistic role. The analysis of exosomes underscored the significance of miR-4738-3p in cellular communication, with an enhanced level of exo-miR-4738-3p antagonizing IL-1β-induced inflammation and promoting cell survival. Conversely, a reduction in exo-miR-4738-3p led to increased cell damage. This study established a clear regulatory relationship between miR-4738-3p and COL1A2, with the nuclear factor kappa B (NF-κB) signaling pathway playing a central role in this regulation. The miR-4738-3p significantly influences the OA-associated inflammation, primarily through modulation of COL1A2 and the NF-κB pathway. Therefore, targeting miR-4738-3p offers a potential therapeutic approach for OA, with exosome miR-4738-3p presenting a promising strategy.

Genome-wide identification of the CNGC gene family and negative regulation of drought tolerance by HvCNGC3 and HvCNGC16 in transgenic Arabidopsis thaliana

Cyclic nucleotide-gated ion channels (CNGCs), as non-selective cation channels, play essential roles in plant growth and stress responses. However, they have not been identified in Qingke (Hordeum vulgare L.). Here, we performed a comprehensive genome-wide identification and function analysis of the HvCNGC gene family to determine its role in drought tolerance. Phylogenetic analysis showed that 27 HvCNGC genes were divided into four groups and unevenly located on seven chromosomes. Transcription analysis revealed that two closely related members of HvCNGC3 and HvCNGC16 were highly induced and the expression of both genes were distinctly different in two extremely drought-tolerant materials. Transient expression revealed that the HvCNGC3 and HvCNGC16 proteins both localized to the plasma membrane and karyotheca. Overexpression of HvCNGC3 and HvCNGC16 in Arabidopsis thaliana led to impaired seed germination and seedling drought tolerance, which was accompanied by higher hydrogen peroxide (H2O2), malondialdehyde (MDA), proline accumulation and increased cell damage. In addition, HvCNGC3 and HvCNGC16-overexpression lines reduced ABA sensitivity, as well as lower expression levels of some ABA biosynthesis and stress-related gene in transgenic lines. Furthermore, Yeast two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that HvCNGC3 and HvCNGC16 interacted with calmodulin/calmodulin-like proteins (CaM/CML), which, as calcium sensors, participate in the perception and decoding of intracellular calcium signaling. Thus, this study provides information on the CNGC gene family and provides insight into the function and potential regulatory mechanism of HvCNGC3 and HvCNGC16 in drought tolerance in Qingke.

Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection

Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production. The Mitogen-Activated Protein kinase MpkA is essential for GT production and self-protection, interacts physically with GliT and GtmA and it is necessary for their regulation and subsequent presence in the vacuoles. The sensor histidine kinase SlnASln1 is important for modulation of MpkA phosphorylation. Our work emphasizes the importance of MpkA and compartmentalization of cellular events for GT production and self-defense.

Cytotoxicity of Anagallis arvensis L. Extracts: Implications for Traditional Healing

Anagallis arvensis L. comprises two species, specifically Anagallis foemina Mill. For centuries, the Navarra region in Spain has employed primulaceae as traditional wound healing remedies. Previous studies have established the antimicrobial and COX-inhibitory properties of this species. However, despite the known cytotoxic effects at high doses or with prolonged oral administration, there is a lack of definitive research to establish their toxicity. In this study, cytotoxicity was assessed using spectrophotometric methods, including the MTT and LDH assays, on PC12 and DHD/K12PROb cells. Notably, DHD/K12PROb cells exhibited heightened sensitivity to the extracts compared to PC12 cells, resulting in reduced cell survival and increased cell damage (LDH release). Significant reductions in cell survival were observed with methanol extracts exceeding 80 mg/ml. These findings suggest that the reported toxic effects in traditional medicine may be attributed to the cytotoxic nature of these plants.

Abstract 176: The Pathological Role of Aldose Reductase in Isolated Cardiomyocytes Undergoing Hypoxia / Reoxygenation After Prior Exposure to High Glucose Concentrations

Hyperglycemia increases the vulnerability of the cardiovascular system to ischemia/reperfusion (IR) injury. There are currently no effective therapeutic strategies. We hypothesized that hyperglycemia would increase glucose flux through the polyol pathway. Aldose reductase (AR) catalyzes the first step of this pathway by converting glucose to sorbitol. This reaction generates more oxidative stress due to the depletion of NADPH and osmotic stress caused by sorbitol accumulation, making the heart more susceptible to IR injury. This study aimed to better understand the injury mechanism in cardiomyocytes after high glucose exposure and IR injury. Confluent cardiomyocytes were exposed for 24 hours to 25, 50, or 100 mM glucose or 25 mM glucose with 25 or 75 mM sucrose concentrations added. The non-metabolizable sugar sucrose was used as an osmolarity control. Epalrestat, an AR inhibitor, was added at 0, 1, or 10 μM per well (n = 18 per group) during glucose or sucrose exposure. Cells were then subjected to 24 hours of hypoxic conditions (glucose-, sucrose- and serum-free media; 0.01% O 2 , 37 °C; hypoxic chamber) or normoxic conditions (complete media; 21% O 2 , 37 °C), followed by a 2-hour reoxygenation period in normoxic conditions. Cell injury was quantified by measurement of lactate dehydrogenase (LDH) release. Data were normalized to 25 mM glucose after control/normoxic conditions without AR inhibitor. A three-way ANOVA was conducted to compare groups, followed by the Holm-Šidák test. Increasing glucose concentrations lead to increased cell damage after hypoxia/reoxygenation. Adding the AR inhibitor during the glucose exposure period reduced LDH release after hypoxia/reoxygenation in a dose-dependent manner. The addition of sucrose did not increase cell injury. The AR inhibitor did not affect cells exposed to sucrose. The polyol pathway may play a dominant role in increased cell injury by hyperglycemia after hypoxia/reoxygenation.

Transcriptomic Responses to Nitrite Degradation by Limosilactobacillus fermentum RC4 and Effect of ndh Gene Overexpression on Nitrite Degradation.

The excessive nitrite residue may increase cell damage and cancer risk. Limosilactobacillu fermentum RC4 exhibited excellent nitrite degradation ability. Herein, the molecular mechanism of nitrite degradation by L. fermentum RC4 was studied by integrating scanning electron microscopy analysis, transcriptomics, and gene overexpression. The results demonstrated that the gene profile of RC4 cultured in MRS broth with 0, 100, and 300 mg/L NaNO2 varied considerably; RC4 responded to nitrite degradation by regulating pyruvate metabolism, energy synthesis, nitrite metabolism, redox equilibrium, protein protection, and signaling. High nitrite concentrations affected the morphology of RC4 with a longer phenotype, rough and wrinkle cell and reduced cell surface hydrophobicity. Moreover, an up-regulated expression of gene ndh encoding NADH dehydrogenase, which provides electrons for nitrite reduction by catalyzing NADH, was identified when RC4 was exposed to nitrite. Overexpression of ndh in RC4 increased the nitrite degradation rate by 2-9.5% in MRS broth with 100 mg/L NaNO2. Thus, the findings of this study could be helpful for the application of L. fermentum to reduce nitrite residues and improve food safety in fermented food products.

FDG-PET versus Amyloid-PET Imaging for Diagnosis and Response Evaluation in Alzheimer's Disease: Benefits and Pitfalls.

In June 2021, the US Federal Drug and Food Administration (FDA) granted accelerated approval for the antibody aducanumab and, in January 2023, also for the antibody lecanemab, based on a perceived drug-induced removal of cerebral amyloid-beta as assessed by amyloid-PET and, in the case of lecanemab, also a presumption of limited clinical efficacy. Approval of the antibody donanemab is awaiting further data. However, published trial data indicate few, small and uncertain clinical benefits, below what is considered "clinically meaningful" and similar to the effect of conventional medication. Furthermore, a therapy-related decrease in the amyloid-PET signal may also reflect increased cell damage rather than simply "amyloid removal". This interpretation is more consistent with increased rates of amyloid-related imaging abnormalities and brain volume loss in treated patients, relative to placebo. We also challenge the current diagnostic criteria for AD based on amyloid-PET imaging biomarkers and recommend that future anti-AD therapy trials apply: (1) diagnosis of AD based on the co-occurrence of cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, (2) therapy efficacy determined by favorable effect on cognitive ability, cerebral metabolism by FDG-PET, and brain volumes by MRI, and (3) neuropathologic examination of all deaths occurring in these trials.

Lipo-MGN nanoparticle hypoxia attenuation-mediated single-dose radiotherapy- and pH/ROS-responsive T1 contrast magnetic resonance imaging in hepatocellular carcinoma

Tumor hypoxia is an important factor for developing resistance to radiation therapy (RT) and presents a bleak prognosis in cancer patients undergoing treatment for RT resistant hepatocellular carcinoma. Here, we present the synthesis of liposome-coated Mn3O4 (MGN) nanoparticles (Lipo-MGN) and investigation of their therapeutic potential with RT utilizing a HepG2 cancer model. According to in vitro research, Lipo-MGN effectively produced oxygen in the presence of H2O2 and significantly reduced the expression of HIF-1 in human HepG2 cells that were under hypoxic conditions. Lipo-MGN reversed the radio-resistance brought on by hypoxia and increased cell damage. When Lipo-MGN and RT were administered together in a HepG2 xenograft mice model, the tumor growth was delayed more than with RT alone. As determined by MR imaging, liposome-MGN also exhibited T1 contrast enhancement in tumor. According to these findings, Lipo-MGNs may increase the impact of RT by focusing tumor hypoxia. Hypoxic, radioresistant HepG2 cancer may be treated with Lipo-MGN in clinical studies.

MiR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation.

Evidence suggests that the microRNA-181 (miR-181) family performs various roles in the pathophysiology of cerebral ischemia and reperfusion injury (CIRI). MiR-181a has been identified as a critical determinant of neuronal survival. Moreover, the significance of miR-181a in controlling neuronal death after CIRI has received little attention. The objective of this study was to assess the role of miR-181a in neuronal cell injury after CIRI. To mimic the in-vitro and in-vivo CIRI, we developed an oxygen-glucose deficiency/reoxygenation (OGD/R) model in SH-SY5Y cells and a transient middle cerebral artery occlusion model in rats. MiR-181a expression was significantly higher in both in-vivo and in-vitro CIRI models. The overexpression of miR-181a increased cell damage and oxidative stress caused by OGD/R, whereas inhibition of miR-181a reduced both. PTEN has also been found to be a direct miR-181a target. PTEN overexpression reduced cell apoptosis and oxidative stress induced by miR-181a upregulation under an OGD/R condition. Furthermore, we found that the rs322931 A allele was related to increased miR-181a levels in IS peripheral blood and higher susceptibility to IS. The current results offer new insights into the understanding of the molecular pathophysiology of CIRI, as well as possible new treatment candidates.

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Algal cell inactivation and damage via cold plasma-activated bubbles: Mechanistic insights and process benefits

Cold plasma-based oxidation, wherein several reactive species are produced by combining a gas with electrical discharges, can treat algal-impacted waters. A novel approach to discharge cold plasma via bubbles, known as cold plasma-activated bubbles (CPABs), has gained attention due to increased interfacial area and residence time of bubbles, thereby effectively transporting reactive species. In this study, the efficacy of air-CPABs and oxygen-CPABs in treating Chlorella vulgaris-laden MilliQ and phosphate buffered saline (PBS) in the immediate and long-term (168 h) was evaluated via flow cytometry. Air-CPABs and O2-CPABs were equally effective in the immediate and long-term for reducing cell numbers (65–100 % MilliQ; 0–45 % PBS) and increasing cell damage and inactivation (100 % in MilliQ and PBS in 3 h and 168 h, respectively). However, O2-CPABs are preferable due to negligible nitrite and nitrate concentrations in the treated water compared to air-CPABs where nitrite and nitrate concentrations were 36–122 mg·L−1 and 42–298 mg·L−1, respectively, thereby, exceeding regulatory guideline limits. After air-CPAB treatment, the ratio of “intact but inactive” cells to “damaged but active” cells in PBS increased from 0.8 to 1 to 1.2–33.6, suggesting that healthy cells were inactivated prior to damage. This ratio declined from 3.6 to 16 to ∼ 1 in O2-CPABs, caused by increasing numbers of “damaged but active” cells. For both, O2− and OH radicals had the greatest impact on algal cell removal in MilliQ (0–28 %); O3 and O2− caused the most damage and inactivation (36–41 %) when using O2-CPABs in PBS. CPAB energy yields (3.95–8.82 × 1010 cells·kWh−1) were comparable to- or ∼ 3–7 × greater than those achieved via non-bubble plasma discharges at relatively lower discharge power (2.2–4.3 kW), indicating that CPABs efficiently utilised the discharged power for algal treatment and promoted sustainability.

Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear. Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker. Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH. All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways. First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.

Effect of Gamma Radiation and Curcuma xanthorrhiza Extract Capsules on Damage Mus musculus Liver Cells

Gamma radiation produces free radicals when interacting with cells. The free radical can be neutralized and caught by an antioxidant compound. This research aimed to analyze the effect of gamma radiation exposure and treated Curcuma xanthorrhiza extract capsules on the cells damage to the mice’s liver. This study used mice of the Balb/c strain with an average body weight of 18-20 grams, aged 6-8 weeks and male. This study required 80 animals for 3 groups, namely K- (without radiation and extract), R- (gamma radiation without extract of Curcuma xanthorrhiza) and R+ (given extract and then irradiated). Radiation exposure was given for 10 minutes, 20 minutes, 30 minutes, 40 minutes and 50 minutes, while Curcuma xanthorrhiza extract was given in 5 different doses, namely, 1.4 g/kg body weight; 2.0 g/kg body weight; 2.6 g/kg body weight; 3.2 g/kg body weight and 3.8 g/kg body weight. The damaging of liver cells is done by analyzing its microscopic picture. The result showed increased exposure time to gamma radiation causes increased cell damage. Cell damage is low in a row of increasing Curcuma xanthorrhiza extract dose. The adequate amount of Curcuma xanthorrhiza extract is 3.8 g/kg body weight.

Antibacterial Activity of Lactic Acid Producing Leuconostoc mesenteroides QZ1178 Against Pathogenic Gallibacterium anatis.

Lactic acid bacteria (LAB) convert carbohydrates into organic acids [mainly lactic acid (LA)], which reportedly have bactericidal activities. Gallibacterium anatis is a Gram-negative bacteria which infects birds, and causes significant economic losses. In this study, we investigated the antibacterial activity of the LA producing, Leuconostoc mesenteroides QZ1178 from Qula (fermented food), against G. anatis, using the Oxford cup method. Our data showed that L. mesenteroides QZ1178 inhibited G. anatis isolates from different origins; however, L. mesenteroides QZ1178 antibacterial activity dropped dramatically at pH 5.5–pH 6. The LA concentration and pH of the liquid broth containing L. mesenteroides QZ1178 after 24 h culture was 29 mg/mL and 3.6, respectively. This concentration (29 mg/mL at pH 3.6) and the antibiotic, cefotaxime (minimum inhibitory concentration (MIC) 2.5 μg/mL) effectively inhibited G. anatis (GAC026) growth as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Gallibacterium anatis treated with LA exhibited extensive cell surface collapse, increased cell damage, cell membrane disruption, and cytoplasmic leakage, indicative of cell lysis. We suggest L. mesenteroides QZ1178 exerts potential antibacterial effects against the poultry pathogen, G. anatis via LA.

The controversial effects of dehydrated powder of Gracilaria birdiae as a food supplement to juvenile male rats

The present study aimed to characterize in vitro antioxidant properties of red algae (Gracilaria birdiae) powder and to investigate its potential protective and antioxidant effects in male rats, with and without co-exposure to a ternary mixture of agrochemicals. The focus was on reproductive and DNA damage parameters, both known as vulnerable targets for oxidative stress induced by this class of toxicants. It is important to emphasize that the dehydrated powder of G. birdiae used in the present study is already commercialized for food purposes. In vitro tests revealed that G. birdiae dehydrated powder preserves important antioxidant features of the algae, demonstrating potential for use as food supplements. On the other hand, in vivo tests showed that dietary supplementation with 5% of the homogenate of dehydrated G. birdiae, per se, impaired spermatogenesis due to increased cell damage and consequent cell death in the seminiferous epithelium, without interfering with antioxidant enzymes and androgenic status of the animals. In addition, no beneficial or protective effect of G. birdiae homogenate was observed in animals co-exposed to the agrochemical mixture. Contrary to expectation, in the experimental conditions presented here, powder of G. birdiae was able to induce reproductive toxicity and provoke DNA damage. The data obtained call attention to the importance of discussing the use of food supplementation in the prevention and maintenance of health and the need for better regulating the processing procedures and market of natural supplements.

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3.

In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.