Amount Of ROS Research Articles

The pathogenesis of ischemic hepatitis

Ischemic hepatitis is inflammation caused by necrosis of liver cells due to ischemia and hypoxia caused by low cardiac output or septic shock. It is often complicated by heart failure or severe septic shock. One of the pathogenesis of ischemic hepatitis is hepatocyte injury caused by ischemia and hypoxia, which results in damage-associated molecular patterns (DAMPs) release and binding to membrane receptors such as toll like receptors (TLRs) to cause inflammatory reactions.The other is when the ischemic liver is reperfused, hepatocyte mitochondrias will produce a large amount of ROS causing ischemia reperfusion injury. These two mechanisms and related molecular pathways are elaborated in this paper.

Selective striatal cell loss is ameliorated by regulated autophagy of the cortex

AimsThe harmful cellular environment leads to brain damage, and each brain subregion exhibits a differential vulnerability to its effects. This study investigated the causes of selectively striatal cell loss in systemic 3-nitropropionic acid (3-NP) infused mice. Main methodsThis study was performed in the neuronal cell line, primary neuron, cultured mouse brain, and mice brain tissues. The 3-NP solution was delivered using an osmotic mini-pump system for 7 days. ROS in brain tissue were detected and evaluated with the signals of CM-H2DCFDA for total cellular ROS and MitoSOX Red for mitochondrial ROS. Cellular ROS and the functional status of mitochondria were assessed with a detection kit and analyzed using flow cytometry. To quantify oxidative damaged DNA, apurinic/apyrimidinic (AP) site numbers in DNA were measured. The protein expression level was assessed using Western blotting, and immunohistochemistry was performed. Cleaved caspase-3 activities were measured by using an enzyme-linked immunosorbent assay (ELISA) kit. Key findingsBy 3-NP, mitochondrial dysfunction was higher in the striatum than in the cortex, and mitochondria-derived ROS levels were higher in the striatum than in the cortex. However, autophagy that may restore the energy depletion resulting from mitochondrial dysfunction occurred comparably less in the striatum than in the cortex. Inhibition of ASK1 by NQDI1 regulates MAPK signaling, apoptosis, and autophagy. Regulated autophagy of the cortex improved non-cell autonomously striatal damaged condition. SignificanceThis study illustrated that the different vulnerabilities of the brain subregions, striatum or cortex, against 3-NP are rooted in different mitochondria-derived ROS amounts and autophagic capacity.

Abstract 1011: Disulfiram superior to ALDH1A1 inhibitor analogs in targeting ovarian cancer stem cells

Abstract Epithelial ovarian cancer (EOC) is a global health burden and remains the fifth leading cause of cancer related death in women worldwide with the poorest five-year survival rate of the gynecological malignancies. Disease recurrence is the major cause of morbidity and mortality of EOC, considered to be driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs). TIC populations in EOC can be identified by the expression of molecular markers such as aldehyde dehydrogenase (ALDH), CD133, Nanog and Sox2. Although the TICs have been characterized, little progress has been made in finding drugs to specifically target this population, which has driven the research and development of novel therapies to prevent relapse. We previously showed that disulfiram, an ALDH inhibitor, effectively targeted TICs in terms of viability, spheroid formation, oxidative stress and also prevented relapse in an in vivo model of EOC. In this study we sought to determine whether specific targeting of ALDH isoenzyme ALDH1A1 would provide similar benefit as the broader pathway inhibition by disulfiram. NCTs 505 and 506 are isoenzyme specific ALDH1A1 inhibitors whose activity was compared to the effects of disulfiram. Following treatment with either the NCTs or disulfiram, the viability of TICs versus adherent cells, sphere formation, oxidative stress and cell death in our in vitro relapse model were measured and compared in OC cell lines. We found that disulfiram decreased the viability of TICs significantly more effectively versus non-TIC cells, while no trend was observed when the cells were treated with the NCTs. Disulfiram also induced greater amounts of ROS than the NCTs and affected the expression of proteins associated with the NFkB and JNK signaling pathways. Comparison of disulfiram to the direct targeting of ALDH1A1 with the NCTs suggests that disulfiram's broader cellular effects are more suitable as a therapeutic to eradicate TICs from tumors and prevent OC relapse. In addition to providing insight into a fitting treatment for TICs, the comparison of disulfiram to NCTs 505 and 506 has increased our understanding of disulfiram's mechanism of action. Further elucidation of disulfiram's mechanism has the potential to reveal additional targets to treat OC TICs and prevent disease recurrence. Citation Format: Michael Caminear, Brittney Harrington, Christina Annunziata. Disulfiram superior to ALDH1A1 inhibitor analogs in targeting ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1011.

CP12 Is Involved in Protection against High Light Intensity by Suppressing the ROS Generation in Synechococcus elongatus PCC7942.

We previously reported that CP12 formed a complex with GAPDH and PRK and regulated the activities of these enzymes and the Calvin–Benson cycle under dark conditions as the principal regulatory system in cyanobacteria. More interestingly, we found that the cyanobacterial CP12 gene-disrupted strain was more sensitive to photo-oxidative stresses such as under high light conditions and paraquat treatment. When a mutant strain that grew normally under low light was subjected to high light conditions, decreases in chlorophyll and photosynthetic activity were observed. Furthermore, a large amount of ROS was accumulated in the cells of the CP12 gene-disrupted strain. These data suggest that CP12 also functions under light conditions and may be involved in protection against oxidative stress by controlling the flow of electrons from Photosystem I to NADPH.

Extraction of Antioxidant Compounds from Blueberry Fruit Waste and Evaluation of Their In Vitro Biological Activity in Human Keratinocytes (HaCaT)

The purpose of this study was to investigate the biological properties of an extract obtained from the waste of blueberry fruit. The study covered the optimization of extraction of antioxidants from blueberry pomace and the determination of antioxidant properties of the extract using HaCaT as the model organism. Research showed that the yield of antioxidants extraction from blueberry waste was dependent on the applied extraction conditions. Based on the mathematical models, the optimal conditions of extraction process in which the maximum quantity of antioxidant compounds is achieved from the waste mass unit, i.e., the relation of the waste mass to the volume of ethanol equal to 1:17.36, and process time equal to 1000 s. The obtained extract was characterized by high antioxidant activity, which was shaped by high content of polyphenols, mainly anthocyanins. Moreover, the extract showed a high ability to protect HaCaT cells from the occurrence of oxidative stress induced by H2O2. Cells treated with the extract and H2O2 generated a lower amount of ROS than cells treated with H2O2 only. The obtained results will be base of further studies on applying the extract in production of diet supplements and functional foods with increased antioxidant activity. Moreover, the main research material is blueberry pomace which is a troublesome waste material for juice producers. Consequently, according to a sustainable development idea, the study results will provide an opportunity to increase interest in the problem of rational use of the waste material to a certain extent.

TLR4/TRAF6/NOX2 signaling pathway is involved in ventilation-induced lung injury via endoplasmic reticulum stress in murine model

In ventilation-induced lung injury (VILI), prolonged nonpathogen-mediated inflammation is triggered as a result of alveolar hyperinflation. In our previous study, we suggested that endoplasmic reticulum (ER) stress-mediated inflammation was involved in VILI, but how ER stress is triggered remains unknown. Toll-like receptor 4 (TLR4) activation plays an important role in mechanical ventilation (MV)-induced lung inflammation, however, it is unknown whether ER stress is activated by TLR4 to participate in VILI. In this study, C57BL/6 mice were exposed to MV with high tidal volumes (HTV 20 ml/kg). Mice were pretreated with TAK-242 the TLR4 inhibitor, C25-140, the TRAF6 inhibitor, or GSK2795039, the NOX2 inhibitor. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to measure lung injury, inflammatory responses and mRNA/protein expression associated with ER stress and the TLR4/TRAF6/NOX2 signaling pathway. Our results indicate that MV with HTV caused the TLR4/TRAF6/NOX2 signaling pathway activation and production of large amounts of ROS, which led to ER stress and NF-κB mediated inflammation in VILI. Furthermore, TLR4/TRAF6/NOX2 signaling pathway inhibition attenuated ER stress response and alleviate lung injury in mice.

Artemisinin co-delivery system based on manganese oxide for precise diagnosis and treatment of breast cancer

Tumor microenvironment (TME) responsive intelligent system can realize the specific release and uniform distribution of chemotherapy drugs in tumor tissues, to achieve high-efficiency and low-toxic treatment of tumors. In this paper, drug delivery system TKD@RBCm-Mn2O3-ART with the above characteristics was constructed. We synthesized hollow mesoporous manganese trioxide (Mn2O3) nanoparticles and firstly found that they owned time-dependent size transformation feature in simulated TME. The particle size decreased from 318 nm to 50 nm and 6 nm at 1 h and 4 h in simulated TME, respectively. Then artemisinin (ART) was loaded into Mn2O3 to realize the co-delivery of Mn2+ and ART. The modification of homologous red cell membrane (RBCm) and TKD peptide was aimed at long circulation and tumor targeting in the body. In vitro results demonstrated that in the presence of GSH, the cumulative drug release percentage could achieve 97.5%. Meanwhile, Mn2O3 exhibited a good imaging capability in tumor, with the relaxation rate of 6.3113 mM−1 s−1. After entering into MCF-7 cells, TKD@RBCm-Mn2O3/ART synchronously released Mn2+ and ART to generate large amount of ROS and induce DNA damage. In vivo results proved TKD@RBCm-Mn2O3/ART could arrive the deep area of solid tumors and achieve accurate diagnosis and treatment of breast cancer.

ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer

BackgroundReactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.MethodsIndocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.ResultsCompared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.ConclusionsLipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.

Oxidative damage in the liver and brain of the rats exposed to frequency-dependent radiofrequency electromagnetic exposure: biochemical and histopathological evidence

The study aimed to discover a link between the liver and brain's functional status due to frequency dependent-radiofrequency electromagnetic radiation (RF-EMR). Forty Wistar rats were randomly classified as control (sham-exposed) and EMR exposed groups. Animals were exposed to 900, 1800, and 2100 MHz with the specific absorption rate (SAR) 0.434 (W/Kg), 0.433 (W/Kg), and 0.453 (W/Kg) respectively. Animal exposure was limited at 1 h/day, 5 days/week for 1 month with a restricted power density (900 MHz- 11.638 µW/m2, 1800- 11.438 µW/m2 and 2100 MHz frequency- 8.237 µW/m2). Exposure at various frequencies showed a frequency-dependent change in the body weight and hematologic parameters (RBCs, WBCs, platelets, hemoglobin, and hematocrit) as compared with the control group (p ≤ 0.01) (p ≤ 0.001). A significant elevation in serum transaminases and bilirubin, urea, uric acid, and creatinine was noted, whereas albumin significantly decreased after EMR exposure (p ≤ 0.01) (p ≤ 0.001). The blood glucose, lipid peroxidation, triglycerides, and cholesterol were elevated while adenosine triphosphatases, acetylcholinesterase, and tissue antioxidants such as glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione Peroxidase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenases were decreased significantly (p ≤ 0.001). Histopathological observations of the liver showed centrilobular mononuclear cell infiltration and swelling in sinusoidal spaces, while in the brain degenerated pyramidal and Purkinje neurons were seen. Furthermore, Substantial evidence was found that the brain is more susceptible to oxidative mutilation compare to the liver of exposed animals. In conclusion, RF-EMR exposure showed oxidative damage to the liver, increasing the incidence of brain damage in a frequency-dependent manner. Highlights EMR exposure showed frequency-dependent toxicity. Alterations in blood profile and modifications in the serological markers. Increasing lipid peroxidation indicating membrane damage. Inhibition of acetylcholinesterase activity affecting cholinergic neurotransmission. EMR exposure resulted in the loss of cellular energy and production of excess amounts of ROS thereby altering several antioxidant enzymes. Histopathological evidence of severe degenerative changes in the liver and brain.

Amelioration of Oxidative Stress Through Supplementation of Self- formulated Anti-oxidant Mixture for Early Recovery and Prophylaxis of Bovine Mastitis in Kashmir Valley

Background: During lactation, mammary epithelial cells exhibit a high metabolic rate and thus produce large amounts of ROS and lipid peroxides in vivo (Jin et al. 2014; Ganguly et al., 2016). A surplus of ROS and the absence of optimal amounts of antioxidants (which neutralize these free radicals or ROS) results in oxidative stress (Lykkesfeldt and Svendsen, 2007). A clinical study was undertaken on Bovine Mastitis in Kashmir valley to study the relation between oxidative stress and clinical mastitis. An attempt was also made to see the effect of supplementation of self-formulated anti-oxidant trace mineral mixture on recovery and prophylaxis of Bovine mastitis through amelioration of oxidative stress.Methods: The oxidative stress was assessed through estimation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO). In addition, blood trace mineral status for copper (Cu), zinc (Zn), manganese (Mn) and selenium (Se) were also assessed in mastitic animals and compared with normal healthy lactating animals. The utility of anti-oxidants in clinical management of mastitis was measured through response to treatment with trace minerals like Cu, Zn, Mn and Se in addition to conventional antibiotic therapy. Two groups of mastitic animals received two therapeutic regimens. Group I animals received antibiotics and self formulated anti-oxidant mixture at therapeutic doses while as Group II animals received only antibiotics (at same dose rate and frequency). Clinical recovery was assessed on the basis of CMT point score, milk somatic cell count and milk biochemistry. For prophylactic study, forty recently parturated lactating animals having susceptibility to occurrence of mastitis were divided into two groups of twenty animals each. One group of animals was supplemented with self-formulated anti-oxidant mixture at prophylactic doses for a period of thirty days so as to see the effect of supplementation on oxidative stress parameters and occurrence of clinical mastitis.Result: A significant decrease was found in the values of SOD, catalase, GSH and Cu, Zn, Mn and Se but a significant increase was found in the values of MDA and NO in clinical cases of mastitis as compared to healthy control group. Therapeutic regimen I proved efficacious than the therapeutic regimen II in treatment of clinical mastitis with higher recovery rates and lesser number of mean days required for recovery in group I than group II animals. The efficacy of prophylactic treatment was monitored by occurrence of mastitis during the course of therapy and one month after therapy. Group I animals did not suffer from clinical mastitis and showed considerable improvement in oxidative stress parameters, milk SCC and blood trace mineral status as compared to group II.

Protective Effects of Alpha Lipoic Acid Against Arsenic Induced Oxidative Stress in Isolated Rat Liver Mitochondria.

Arsenic as a heavy metal and toxic pollutant has been established that has the hepatotoxic effect in animal and human models. Previous studies showed that mitochondria as the first target of arsenic toxicity has a pathogenic role in liver diseases. This study investigated alpha lipoic acid (ALA) as an antioxidant could ameliorate against liver toxicity induced by arsenic in rat mitochondria. First, mitochondria were isolated by the liver tissue centrifugation protocol. Then, isolated mitochondria were exposed with different concentrations of ALA and arsenic in different times for receiving the optimum dose and time. Finally, mitochondria were pretreated with the optimum concentrations and times of ALA and then treated with optimum concentration and time of arsenic (160 μg/ml; 30 min). The results demonstrated a significant decrease in total mitochondrial dehydrogenase activity (mitochondrial complex II) by 3, 4 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay after arsenic exposure. Mitochondria treated with arsenic also showed a significant increase in ROS generation, MMP, and MDA levels. The activity of mitochondrial catalase and mitochondrial GSH significantly decreased after exposure of mitochondria with arsenic. Pretreatment of mitochondria with ALA improved mitochondrial complex II activity; decreased mitochondrial membrane damage, MDA, and ROS amounts; and ameliorated mitochondrial GSH levels and mitochondrial catalase activity. These findings revealed that arsenic induced oxidative stress and mitochondria dysfunction, while ALA improved mitochondrial function through increasing of antioxidant defense or preserving of complex II, but suggested that ALA could prevent from mitochondria dysfunction.

Photocatalytic performance and antibacterial mechanism of Cu/Ag-molybdate powder material

Mo-containing semiconductors have attracted significant attention because of their unique photosensitivity, rendering superior visible-light photocatalytic activity. The current study utilizes a combination of theoretical and experimental approaches to systematically investigate the correlation between crystal structure, morphology, photocatalytic activity and stability of rod-shaped copper molybdate (Cu3Mo2O9) and layered silver molybdate nanomaterials (Ag2MoO4). At the same time, Escherichia coli (E. coli) is used, as a model gram-negative bacterium, to demonstrate antimicrobial properties of Cu3Mo2O9 and Ag2MoO4. The results reveal that as-prepared Cu3Mo2O9 and Ag2MoO4 exhibit superior antibacterial performance and excellent photocatalytic activity. Finally, the antibacterial mechanism is proposed based on experimental results, revealing that the sterilization is achieved by ion sterilization and formation of a certain amount of ROS and medium acidification. The present work enhances our understanding of the Cu/Ag-molybdate antibacterial mechanism and demonstrates the feasibility of constructing Mo-containing photocatalysts with high photocatalytic and antimicrobial activities.

Why Is the Invasive Plant Sphagneticola trilobata More Resistant to High Temperature than Its Native Congener?

Climate change and invasive alien species threaten biodiversity. High temperature is a worrying ecological factor. Most responses of invasive plants aimed at coping with adversity are focused on the physiological level. To explore the molecular mechanisms underlying the response of an invasive plant (Sphagneticola trilobata L.) to high temperature, using a native species (Sphagneticola calendulacea L.) as the control, relevant indicators, including photosynthetic pigments, gas exchange, chlorophyll fluorescence, the antioxidant system, and related enzyme-coding genes were measured. The results showed that the leaves of S. calendulacea turned yellow, photosynthetic pigment content (Chl a, Chl b, Car, Chl) decreased, gas exchange (Pn) and chlorophyll fluorescence parameters (Fv/Fm, ΦPSII) decreased under high temperature. It was also found that high temperature caused photoinhibition and a large amount of ROS accumulated, resulting in an increase in MDA and relative conductivity. Antioxidant enzymes (including SOD, POD, CAT, and APX) and antioxidants (including flavonoids, total phenols, and carotenoids) were decreased. The qPCR results further showed that the expression of the PsbP, PsbA, and RubiscoL, SOD, POD, CAT, and APX genes was downregulated, which was consistent with the results of physiological data. Otherwise, the resistance of S. trilobata to high temperature was better than that of S. calendulacea, which made it a superior plant in the invasion area. These results further indicated that the gradual warming of global temperature will greatly accelerate the invasion area of S. trilobata.

Comparative proteomic analysis of parasitic loranthus seeds exposed to dehydration stress

Parasitic loranthus [Taxillus chinensis (DC.) Danser] is an important medicinal plant that produces recalcitrant seeds that are sensitive to dehydration. Desiccation tolerance is critical for the survival of recalcitrant seeds in low-moisture environments. Clarifying how these seeds respond to desiccation is important for long-term conservation. Thus, the viability, germination, microstructure, and antioxidant enzyme activities of dehydrated parasitic loranthus seeds were investigated. Diverse organelles were degraded or deformed during dehydration treatments. Additionally, superoxide dismutase and catalase activities gradually decreased in response to desiccation stress. A proteomic analysis involving TMT-labeling and LC–MS/MS were performed. A total of 1479 proteins were identified, of which 141 were differentially expressed proteins (DEPs) at 16 and 36 h after initiating the dehydration treatments. A functional annotation based on gene ontology revealed that the DEPs were mainly localized in chloroplasts and were related to energy metabolism, responses to stimuli, and the regulation of biological processes. A KEGG pathway enrichment analysis determined that several of the identified proteins were associated with signal transductions, photosynthesis, and glycolysis/gluconeogenesis. The results suggest that the efficient removal of excessive ROS amounts may be crucial for promoting parasitic loranthus seed germination under dehydration stress conditions. A series of candidate dehydration stress-related proteins were identified and may be relevant for enhancing the dehydration tolerance of the recalcitrant seeds. To the best of our knowledge, this is the first study to elucidate the possible molecular mechanisms underlying the sensitivity of recalcitrant parasitic loranthus seeds to dehydration via a proteomic analysis involving TMT-labeling.

Evaluation of cell biomarkers as in vitrophotoprotective assays for sunscreen formulations

Objectives: The aim of this study was to evaluate cellular indicators, which change with exposure to ultraviolet (UV) radiation and can be used as parameters for measuring sunscreens efficiency. Methods: Commercial strains of L929 and HaCaT cells (skin dermis and epidermis, respectively), from the cell bank of Rio de Janeiro, were exposed to different doses of UVA (350 nm) and UVB (309 nm) radiation. The evaluation of the photoprotective potential of sunscreens was analyzed with cell viability, lipid peroxidation and ROS generation tests. Samples of sunscreen with SPF values ranging from 15 to 60 were applied to a quartz plate superimposed on the top of a microplate containing the cell culture, and then the system was irradiated. Results: The viability and lipid peroxidation of the two cell lines remained unchanged after exposure to UVA radiation. When exposed to UVB radiation, the reduction in viability and the increase in lipid peroxides were dose-dependent, that is, they varied from 3.15% to 95.4%, and from 1.2 to 42.7 nM MDA/pg protein, respectively, both for the L929 strain. The dose of 0.5 J/cm2 reduced by 41.4%±1.67 the number of viable cells, and the dose of 30 J/cm2 promoted the oxidation of 42.7 nM of MDA/pg protein. These doses were selected to evaluate the photoprotective effectiveness of commercial sunscreens. Sunscreens exposed to UVB rays could prevent the loss of cell viability (viability remained around 100% for higher SPF) and the formation of lipid peroxides (30 to 80% reduction of peroxide levels). None of the two cell strains, submitted to UVB radiation, formed amounts of intracellular ROS in a dose-dependent manner. Under exposure to UVA radiation, only the HaCaT cell line produced the largest amounts of ROS in a dose-dependent manner. After treating these cells with photoprotective formulations (20 J/cm2), the researchers observed a reduction in the amount of ROS formed. Conclusions: The parameters of cell viability and lipid peroxidation were promising to evaluate the photoprotective capacity of sunscreens against UVB radiation. The generation of ROS expressed in the HaCaT strain can discriminate the photoprotective potential of formulations against UVA radiation, as sunscreens reduced the formation of ROS. These results suggest that in vitro tests that evaluate the damage caused to cells can predict cellular indicators of the photoprotective effectiveness of sunscreens and contribute to minimize these tests in the initial phase of product research and development.

PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway.

A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.

ROS as Regulators of Cellular Processes in Melanoma.

In this review, we examine the multiple roles of ROS in the pathogenesis of melanoma, focusing on signal transduction and regulation of gene expression. In recent years, different studies have analyzed the dual role of ROS in regulating the redox system, with both negative and positive consequences on human health, depending on cell concentration of these agents. High ROS levels can result from an altered balance between oxidant generation and intracellular antioxidant activity and can produce harmful effects. In contrast, low amounts of ROS are considered beneficial, since they trigger signaling pathways involved in physiological activities and programmed cell death, with protective effects against melanoma. Here, we examine these beneficial roles, which could have interesting implications in melanoma treatment.

Effects of Strong Acidic Electrolyzed Water in Wound Healing via Inflammatory and Oxidative Stress Response.

Strong acidic electrolyzed water (StAEW) is known to inactivate microorganisms but is not fully explored in the medical field. This study is aimed at exploring StAEW as a potential wound care agent and its mechanism. StAEW (pH: 2.65, ORP: 1159 mV, ACC: 32.1 ppm) was sprayed three times a day to the cutaneous wounds of hairless mice for seven days. Wound morphological and histological features and immune-redox markers were compared with saline- (Sal-) and alcohol- (Alc-) treated groups. Results showed that the StAEW group showed a significantly higher wound healing percentage than the Sal group on days 2, 4, 5, and 6 and the Alc group on day 4. The StAEW group also showed earlier mediation on proinflammatory cytokines such as tumor necrosis factor-α, interleukin- (IL-) 6, IL-1β, and keratinocyte chemoattractant. In addition, basic fibroblast growth factor and platelet-derived growth factor were found to be significantly changed in favor of the fibroblast synthesis and angiogenesis. In line, the StAEW group showed a controlled amount of ROS and significantly decreased compared to the Alc group. The StAEW group also favored oxidative stress balance through antioxidant responses. Additionally, matrix metalloproteinases (MMP) 9 and MMP1 were also modulated for keratinocyte and cell migration. Taken together, this study has proven the wound healing effect of StAEW and its earlier mediation through oxidative and inflammatory responses.

High photocatalytic performance of Bi2O(OH)2SO4: Based on dual anion synergistic effect

A series of Bi2O(OH)2SO4 samples have been successfully synthesized via the hydrothermal method by changing the concentrations of Na2SO4, which exhibit a straw-like structure. Herein, the sample with the addition of Na2SO4 was 1.5 mmol (BS-1.5) exhibiting the best photocatalytic performance due to the role of SO42− anion groups. In addition, the exceedingly positive valence band (VB, 4.35 eV) is contributing to the production of OH. Furthermore, an amount of ROS is produced due to the synergistic effect of SO4− and OH−, and result in the excellent catalytic performance. In summary, Bi2O(OH)2SO4 is suitable for practical application in the field of the water purification.

Zinc-pretreatment triggers glutathione and Nrf2-mediated protection against inorganic mercury-induced cytotoxicity and intrinsic apoptosis in PC12 cells

Mercury (Hg) is a hazardous metal, poses environmental problems with severe human health effects; whereas zinc (Zn) is an essential micronutrient with antioxidant properties. The purpose of this research was to investigate the effect of Zn on inorganic Hg-induced cytotoxicity in the PC12 cells. The cells were treated with HgCl2 (5 μM) for 48 h with/without 1 h prior ZnCl2-treatment (100 μM) and deliberated for further analysis. After 48 h of incubation with only Hg2+, the cell showed reduced cell viability, compromised cell membrane, DNA degradation, depleted glutathione level, ROS generation and drastically increased apoptosis. Subsequently, Hg2+-treated cells demonstrated a significant downregulation of akt, mTOR, ERK1, Nrf2, HO1, Bcl-2, Bcl-xL, and upregulation of p53, Bax, cytochrome c and cleaved caspase 3, indicating intrinsic apoptosis induction. However, cells pretreated with Zn2+ before Hg2+-exposure showed a significant improvement in cell viability, cell membrane, DNA damage, glutathione level, ROS amount and apoptotic cells, with a significant upregulation in mTOR, akt, ERK1, Nrf2, HO1, Bcl-2 and Bcl-xL, and downregulation in p53, Bax, cytochrome c and cleaved caspase 3, indicating inhibition of apoptosis. The findings suggested that Zn2+-pretreatment not only improves glutathione content but also induces activation of Nrf2-HO1 pathway, which would tend to suppress Hg-cytotoxicity.