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This study aimed to biochemically and histopathologically investigate the effect of sunitinib on oxidative testicular damage induced by ischemia/reperfusion in rats.Experimental animals were divided into three groups of six rats each: testicular torsion-detorsion (TTD), sunitinib+testicular torsion-detorsion (STD), and sham control (SC). Sunitinib (25mg/kg) was administered orally to the STD group by gavage. Normal saline (0.9% NaCl) was administered orally to the TTD and control groups as the solvent. One hour after administration of sunitinib and 0.9% NaCl, all animal groups were done torsion-detorsion. Then, all the rats were killed by high-dose anesthesia, and their testicles were removed. Biochemical and histopathological examinations were performed on the removed testicular tissues.Malondialdehyde; it was observed that the results in the STD group were close to those of the SC group and statistically significant lower compared to the TTD group (p=0.001). The glutathione values were statistically significantly higher in the STD group compared to the TTD group (p0.001). Nuclear factor kappa B values, revealing a statistically significant difference between the TTD and STD groups (p0.001). The TNF-α levels were measured and indicating that the results of the STD group were statistically significantly lower than those of the TTD group (p0.001). Histopathologically, animal tissues given sunitinib were observed to resemble normal tissues.Sunitinib was shown to prevent histopathological changes in testicular tissue against ischemia/reperfusion damage.

The induction of oxidative species, driven by oscillating electric field (E), has recently emerged as an effective approach for tumor inhibition, so-called electrodynamic therapy (EDT). While it offers a series of advantages attracting considerable attention, the fundamental mechanism and improvement strategies for EDT approach are being endeavored extensively with the aid of new material explorations. An interesting phenomenon observed in early studies is that the on-site concentration of chloride ion is highly favored for the induction of oxidative species and the efficacy of tumor inhibition. Following this discovery ignored previously, here for the first time, fine Pt/Cu alloy nanoparticles (PtCu3 NPs) are integrated with chloride ion transporter (CIT) for EDT-based combinational therapy. In this system, while PtCu3 NPs induce oxidative species under an electric field, it also effectively transforms endogenous H2O2 into •OH and consumes intracellular glutathione (GSH). More importantly, with the aid of CIT, PtCu3-PEG@CIT NPs promote the intracellular concentration of chloride ion (Cl−) by transporting extracellular Cl−, facilitating the generation of oxidative species considerably. Meanwhile, CIT delivered intracellularly increases lysosomal pH, leading to the disruption of cellular autophagy and weakening the treatment resistance. In consequence, significant tumor inhibition is enabled both in vitro and in vivo, due to the combination of unique characteristics offered by PtCu3-PEG@CIT.

Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition. Herein, an injectable microsphere (MS@MCL) for local lactate exhaustion was constructed by grafting manganese dioxide (MnO2) -lactate oxidase (LOX) composite nanozyme on microfluidic hyaluronic acid methacrylate (HAMA) microspheres via chemical bonds, achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo. The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency. Furthermore, chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement. It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells (NPCs) in vitro. In the rat degenerative intervertebral disc model caused by lactate injection, MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix (ECM) degradation as well as inflammatory damage in vivo. Altogether, this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.

Background: The major hurdles for successful cancer treatment are drug resistance and invasiveness developed by breast cancer stem cells (BCSC). Objective: As these two processes are highly energy-dependent, the identification of the main ATP supplier required for stem cell viability may result advantageous in the design of new therapeutic strategies to deter malignant carcinomas. Methods: The energy metabolism (glycolysis and oxidative phosphorylation, OxPhos) was systematically analyzed by assessing relevant protein contents, enzyme activities, and pathway fluxes in BCSC. Once identified as the main ATP supplier, selective energy inhibitors and canonical breast cancer drugs were used to block stem cell viability and metastatic properties. Results: OxPhos and glycolytic protein contents, as well as HK and LDH activities were several times higher in BCSC than in their parental line, MCF-7 cells. However, CS, GDH, COX activities, and both energy metabolism pathway fluxes were significantly lower (38-86%) in BCSC than in MCF-7 cells. OxPhos was the main ATP provider (>85%) in BCSC. Accordingly, oligomycin (a specific and potent canonical OxPhos inhibitor) and other non-canonical drugs with inhibitory effect on OxPhos (celecoxib, dimethylcelecoxib) significantly decreased BCSC viability, levels of epithelial-mesenchymal transition proteins, invasiveness, and induced ROS over-production, with IC50 values ranging from 1 to 20 μM in 24 h treatment. In contrast, glycolytic inhibitors (gossypol, iodoacetic acid, 3-bromopyruvate, 2-deoxyglucose) and canonical chemotherapeutic drugs (paclitaxel, doxorubicin, cisplatin) were much less effective against BCSC viability (IC50> 100 μM). Conclusion: These results indicated that the use of some NSAIDs may be a promising alternative therapeutic strategy to target BCSC.

Herein, we report an unprecedented regiospecific oxidative Mizoroki-Heck type reaction for the synthesis of ɑ-difluoromethyl homoallylic alcohols. The reaction shows broad substrate scopes and high functional group tolerance. Late-stage functionalization of complex biologically active molecules demonstrates the synthetic potential of this transformation. Mechanistic study supports the involvement of MnBr2 catalyzed radical 1,2-silyl transfer.

SIGNIFICANCE The imbalance in redox homeostasis is known as oxidative stress, which is relevant to many diseases such as cancer, arteriosclerosis, and neurodegenerative disorders. Overproduction of reactive oxygen species (ROS) is one of the factors that trigger the redox state imbalance in vivo. ROS have high reactivity and impair biomolecules, while antioxidants and antioxidant enzymes, such as ascorbate and glutathione, reduce the overproduction of ROS to rectify the redox imbalance. Owing to this, redox monitoring tools have been developed to understand the redox fluctuations in oxidative stress-related diseases. Recent Advances: In an attempt to monitor redox substances, including ROS and radical species, versatile modalities have been developed, such as electron spin resonance, chemiluminescence, and fluorescence. In particular, many fluorescent probes have been developed that are selective for ROS. This has significantly contributed to understanding the relevance of ROS in disease onset and progression. CRITICAL ISSUES To date, the dynamics of ROS and radical fluctuation in in vivo redox states remain unclear, and there are few methods for the in vivo detection of redox fluctuations. FUTURE DIRECTIONS In this review, we summarize the development of radiolabeled probes for monitoring redox-relevant species by nuclear medical imaging that is applicable in vivo. In the future, translational research is likely to be advanced through the development of highly sensitive and in vivo applicable detection methods, such as nuclear medical imaging, to clarify the underlying dynamics of ROS, radicals, and redox substances in many diseases.

Introduction: This research was conducted to assess the effect of myo-inositol (MYO) in the freezing extender on the semen quality and oxidative stress parameters of frozen–thawed bull sperm. Mater...

Background The central clock of the suprachiasmatic nucleus (SCN) controls the metabolism of glucose and is sensitive to glucose shortage. However, it is only beginning to be understood how metabolic signals such as glucose availability regulate the SCN physiology. We previously showed that the ATP-sensitive K+ channel plays a glucose-sensing role in regulating SCN neuronal firing at times of glucose shortage. Nevertheless, it is unknown whether the energy-demanding Na+/K+-ATPase (NKA) is also sensitive to glucose availability. Furthermore, we recently showed that the metabolically active SCN constantly extrudes H+ to acidify extracellular pH (pHe). This study investigated whether the standing acidification is associated with Na+ pumping activity, energy metabolism, and glucose utilization, and whether glycolysis- and mitochondria-fueled NKAs may be differentially sensitive to glucose shortage. Methods Double-barreled pH-selective microelectrodes were used to determine the pHe in the SCN in hypothalamic slices. Results NKA inhibition with K+-free (0-K+) solution rapidly and reversibly alkalinized the pHe, an effect abolished by ouabain. Mitochondrial inhibition with cyanide acidified the pHe but did not inhibit 0-K+-induced alkalinization. Glycolytic inhibition with iodoacetate alkalinized the pHe, completely blocked cyanide-induced acidification, and nearly completely blocked 0-K+-induced alkalinization. The results indicate that glycolytic metabolism and activation of Na+ pumping contribute to the standing acidification. Glucoprivation also alkalinized the pHe, nearly completely eliminated cyanide-induced acidification, but only partially reduced 0-K+-induced alkalinization. In contrast, hypoglycemia preferentially and partially blocked cyanide-induced acidification. The result indicates sensitivity to glucose shortage for the mitochondria-associated oxidative glycolytic pathway. Conclusion Glycolytic metabolism and activation of glycolysis-fueled NKA Na+ pumping activity contribute to the standing acidification in the SCN. Furthermore, the oxidative and non-oxidative glycolytic pathways differ in their glucose sensitivity and utilization, with the oxidative glycolytic pathway susceptible to glucose shortage, and the non-oxidative glycolytic pathway able to maintain Na + pumping even in glucoprivation.

Abstract: Aging is defined as the functional loss of tissues and organs over time. This is a biological, irreversible, progressive, and universal process that results from genetic and environmental factors, such as diet, physical activity, smoking, harmful alcohol consumption, and exposure to toxins, among others. Aging is a consequence of molecular and cellular damage built up over time. This damage begins with a gradual decrease in physical and mental capacity, thus increasing the risk of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Neuronal, functional, and structural damage can be explained by an imbalance among free radicals, reactive oxygen species, reactive nitrogen species, and antioxidants, which finally lead to oxidative stress. Due to the key role of free radicals, reactive oxygen species, and reactive nitrogen species, antioxidant therapy may reduce the oxidative damage associated with neurodegeneration. Exogenous antioxidants are molecules that may help maintain the balance between the formation and elimination of free radicals, thus protecting the cell from their toxicity. Among them, polyphenols are a broad group of secondary plant metabolites with potent antioxidant properties. Here, we review several studies that show the potential role of polyphenol consumption to prevent, or slow down, harmful oxidative processes linked to neurodegenerative disorders.

Although sorafenib (Sora) shows improved efficacy in clinical liver cancer therapy, its therapeutic efficacy is still greatly limited due to side effects as well as drug resistance. Thus new drug intervention strategies are imperative. Our research showed the combined application of Dihydroartemisinin (DHA) and Sora had a synergistic inhibitory effect on HepG2 and SW480 cells, and DHA enhanced Sora efficacy on xenograft tumor in nude mice. DHA and Sora significantly inhibited the cell energy metabolism by decreasing the glycolysis rate and ATP synthesis rate of oxidative phosphorylation and induced ferroptosis by increasing the level of lipid reactive oxygen species (L-ROS), labile iron pool (LIP) as well as malondialdehyde (MDA) and decreasing the level of glutathione (GSH) in HepG2 cells. In addition, DHA and Sora significantly decreased the levels of SLC7A11 (xCT), GCLC, GPX4, and HO-1 protein in HepG2 cells. Importantly, the above-mentioned indicators changed more significantly after the combined application of DHA and Sora as compared with Sora. In conclusion, DHA and Sora had the same mechanism, and the combined application of them could have a synergistic anti-tumor effect by inducing ferroptosis and inhibiting energy metabolism in HepG2 cells.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two most common subtypes of lung cancer. Here, to identify new, targetable molecular properties of both subtypes, we monitored changes in the levels of heme- and oxidative phosphorylation (OXPHOS)-related proteins during lung tumorigenesis. Heme is a central molecule for oxidative metabolism and ATP generation via OXPHOS. Notably, both lung ADC and SCC tumors can be induced in the genetically engineered KLLuc mouse model harboring the G12D Kras mutation and a conditional Lkb1 knockout. We found that the levels of the rate-limiting heme synthesis enzyme ALAS1 and uptake protein SLC48A1, along with OXPHOS complex subunits, progressively increased as lung tumorigenesis advanced. Our data demonstrated that elevated levels of heme- and OXPHOS-related proteins were associated with both ADC and SCC. Importantly, treatment of KLLuc mice with a heme-sequestering protein, HeSP2, that inhibits heme uptake in tumor cells effectively arrested lung tumor progression, and both ADC and SCC tumors were strongly suppressed. Additionally, HeSP2 effectively suppressed the growth of both SCC and ADC tumor xenografts in NOD/SCID mice. Further analyses indicated that HeSP2 effectively diminished OXPHOS in both ADC and SCC, reduced angiogenesis, alleviated tumor hypoxia, and suppressed cell proliferation. These results show that the advancing of lung tumorigenesis requires progressive increase in cellular heme synthesis and uptake, leading to intensified OXPHOS activity and ATP generation and promoting aggressive tumorigenic functions. Implications: Heme sequestration is an effective strategy for the suppression of both ADC and SCC tumor initiation and development.

This study investigated the effects of mung bean protein (MPI) and a MPI-polyphenol complex on oxidative stress levels and intestinal microflora in a D-galactose-induced aging mouse model. MPI and MPI-polyphenol complex intervention significantly increased activity of superoxide dismutase (SOD) and catalase and other antioxidant enzymes, improved the abundance and diversity of intestinal flora, and decreased the Firmicutes to Bacteroidetes ratio. The addition of MPI and MPI-polyphenol complex can help the proliferation of Bacteroidetes, Bifidobacterium and Roseburia in the intestinal tract of aging mice, and inhibit the growth of Firmicutes and Ruminococcus. MPI significantly upregulated five pathways related to lipid and energy metabolism. Roseburia and Muribaculaceae were negatively correlated with malondialdehyde levels and positively correlated with SOD and other antioxidant enzyme indices. Our findings showed that MPI and MPI-polyphenol complexes can delay aging in mice by reducing oxidative damage and regulating intestinal flora. We also found a strong relationship between the abundance of intestinal flora and the levels of oxidative stress-related enzymes. This study provides theoretical support for the health and anti-aging benefits of mung bean food products.

The Ca2+ buffering capacity of mitochondria maintains the balance of cell physiological activities. The exogenous reactive oxygen species (ROS) can be used to break the balance, resulting in mitochondrial dysfunction and irreversible cell apoptosis. Herein, the CaCO3-based tumor microenvironment (TME) responsive nanoplatform (CaNPCAT+BSO@Ce6-PEG) was designed for oxygen/GSH depletion-boosted photodynamic therapy (PDT) and mitochondrial Ca2+-overloading synergistic therapy. In acidic TME, CaCO3 decomposed and released the cargos (catalase (CAT), buthionine sulfoximine (BSO), chlorin e6 (Ce6), and Ca2+). The tumor hypoxia and reductive microenvironment could be significantly reversed by CAT and BSO, which greatly enhanced the PDT efficacy. The generated 1O2 during PDT process not only directly killed cancer cells but also destroyed the Ca2+ buffering capacity, leading to the mitochondrial Ca2+-overloading. The increased Ca2+ concentration promoted the process of oxidative phosphorylation and inhibited the production of adenosine triphosphate (ATP), resulting in the acceleration of cell death. Under the joint action of enhanced PDT and mitochondrial Ca2+-overloading, the CaNPCAT+BSO@Ce6-PEG NPs showed remarkable synergistic effects in tumor inhibition without any side effects. STATEMENT OF SIGNIFICANCE: In the manuscript, a CaCO3-based nano-platform for tumor microenvironment response was designed. With the decomposition of CaNPCAT+BSO@Ce6-PEG NPs in the acidic tumor microenvironment, the released catalase (CAT) and buthionine sulfoximine (BSO) could relieve the tumor hypoxia and inhibit GSH production. Under 660 nm laser irradiation, the photodynamic effect was enhanced and caused apoptosis. Meanwhile, the Ca2+ buffering capacity was destroyed which led to the mitochondrial Ca2+-overloading. The synergistic effect of enhanced PDT and mitochondrial Ca2+-overloading made the CaNPCAT+BSO@Ce6-PEG NPs present remarkable antitumor performance.

Kupffer cells are a key source of reactive oxygen species (ROS) and are implicated in the development of steatohepatitis and fibrosis in nonalcoholic steatohepatitis (NASH). We recently developed a polythiolated and mannosylated human serum albumin (SH-Man-HSA), a nano-antioxidant that targets Kupffer cells, in which the mannosyl units on albumin allows their specific uptake by Kupffer cells via the mannose receptor C type 1 (MRC1), and in which the polythiolation confers antioxidant activity. The aim of this study was to investigate the therapeutic potential of SH-Man-HSA in NASH model mice. In livers from mice and/or patients with NASH, we observed a reduced blood flow in the liver lobes and the down-regulation in MRC1 expression in Kupffer cells, and SH-Man-HSA alone failed to improve the pathological phenotype in NASH. However, the administration of a nitric oxide (NO) donor restored hepatic blood flow and increased the expression of the mannose receptor C type 2 (MRC2) instead of MRC1. Consequently, treatment with a combination of SH-Man-HSA and an NO donor improved oxidative stress-associated pathology. Finally, we developed a hybrid type of nano-antioxidant (SNO-Man-HSA) via the S-nitrosation of SH-Man-HSA. This nanomedicine efficiently delivered both NO and thiol groups to the liver, with a hepatoprotective effect that was comparable to the combination therapy of SH-Man-HSA and an NO donor. These findings suggest that SNO-Man-HSA has the potential for functioning as a novel nano-therapy for the treatment of NASH.

This review highlights the biological importance of mitochondrial energy metabolism and the applications of multiple optical/electrochemical approaches to determine energy metabolites. Mitochondria, the main sites of oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis, provide the majority of energy required by aerobic cells for maintaining their physiological activity. They also participate in cell growth, differentiation, information transmission, and apoptosis. Multiple mitochondrial diseases, caused by internal or external factors, including oxidative stress, intense fluctuations of the ionic concentration, abnormal oxidative phosphorylation, changes in electron transport chain complex enzymes and mutations in mitochondrial DNA, can occur during mitochondrial energy metabolism. Therefore, developing accurate, sensitive, and specific methods for the in vivo and in vitro detection of mitochondrial energy metabolites is of great importance. In this review, we summarise the mitochondrial structure, functions, and crucial energy metabolic signalling pathways. The mechanism and applications of different optical/electrochemical methods are thoroughly reviewed. Finally, future research directions and challenges are proposed.

Background: Age-dependent toxic effects of organophosphorus pesticides (OPs) have not been fully understood. The current study aimed to investigate the cardiotoxic damage of chlorpyrifos (CPF) by evaluating oxidative modifications in young (2-month old), middle-aged (10- month old), and aged (20-month old) rats. Objective: Five mg/kg of CPF was administered orally for 45 days to young, middle-aged, and aged male Wistar rats. In the end, animals were anesthetized and the heart of each rat was dissected for biochemical assay. Methods: Malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) were assessed in the cardiac tissue of rats. Results: The results indicated an increase in the levels of MDA and NO, and also a decline in the levels of GSH and TAC as well as a decrease in the SOD activity in the heart of aged rats compared with young rats. CPF administration deteriorated these changes in the heart of exposed rats compared with the age-matched controls. Additionally, these oxidative modifications were more severe in aged rats versus other age. Conclusion: In conclusion, advancing age may increase oxidative changes in the heart of animals exposed to CPF. It is suggested that aging can affect cardiac toxicity induced by OPs.

1,3,5-Tri-O-caffeoyl quinic acid is a caffeoylquinic acid derivative isolated from the roots of Arctium lappa L. Our previous studies have revealed that the ethyl acetate extract of the roots of A. lappa L. and the caffeoylquinic acids contained in it possess antioxidant properties, especially 1,3,5-tri-O-caffeoyl quinic acid. The present study aimed to investigate the protective effects of 1,3,5-tri-O-caffeoyl quinic acid against hydrogen peroxide-induced oxidative stress and explore the underlying mechanism. We found that 1,3,5-tri-O-caffeoyl quinic acid prevented the decline of cell viability and excessive release of lactate dehydrogenase induced by hydrogen peroxide. In addition, Hoechst 33 342 staining and Annexin V-PI double staining showed that 1,3,5-tri-O-caffeoyl quinic acid inhibited hydrogen peroxide-induced neuronal cell apoptosis. 1,3,5-Tri-O-caffeoyl quinic acid reduced the excessive production of intracellular reactive oxygen species, decreased the malondialdehyde content, and improved the activity of superoxide dismutase. Furthermore, 1,3,5-tri-O-caffeoyl quinic acid restored the loss of mitochondrial membrane potential in SH-SY5Y cells induced by hydrogen peroxide. 1,3,5-Tri-O-caffeoyl quinic acid downregulated the overexpression of proapoptotic proteins, including Bax, cytochrome c, cleaved caspase-9, and cleaved caspase-3 as well as promoted the expression of the antiapoptotic protein Bcl-2. Moreover, the phosphorylation of mitogen-activated protein kinases induced by hydrogen peroxide was inhibited by 1,3,5-tri-O-caffeoyl quinic acid. Pretreatment with 1,3,5-tri-O-caffeoyl quinic acid also promoted the activation of phosphorylated Akt. Taken together, these findings suggest that 1,3,5-tri-O-caffeoyl quinic acid exerts protective effects against hydrogen peroxide-induced neuronal apoptosis. In addition, inhibition of the mitogen-activated protein kinase signaling pathway and the activation of Akt are implicated in the antioxidant activity of 1,3,5-tri-O-caffeoyl quinic acid, giving new insight in searching for a compound with antioxidant activity for the treatment of oxidative stress-associated neurological diseases.

Aerobic oxidative desulfurization (AODS) represents a sustainable way to deeply desulfurize transportation fuels through a high-performance catalyst to convert thiophenes into sulfones in an effici...

The installation of (benzo)thiophene-containing biaryls via coupling reactions has become a staple in designing photoelectric materials. Undeniably, C-H/C-H cross-coupling reactions between two (hetero)aromatics would be a shortcut toward these structural fragments. While more reliable cross-coupling technologies are well-established to provide C2-arylated (benzo)thiophenes, efficient methods that arylate the C3-position remain underdeveloped. Herein we provide insight into the factors that determine regioselectivity switching for these cross-coupling reactions. X-ray crystallographic analysis gives solid evidence for the key roles of triflate in regioselective dearomatization and acetate in base-assisted anti-β-deprotonated rearomatization. The first isolation and X-ray characterization of a medium-sized dearomatized cyclometalated adduct involving both substrates provide extra insight into aerobic oxidative Ar-H/Ar-H cross-coupling reactions. The mechanistic breakthrough incubates the first example, enabling C-H/C-H-type C3-arylation of benzothiophenes. Finally, this chemistry is used to design blue-emitting thermally activated delayed fluorescence (TADF) materials with a helicene conformation that exhibit a high maximum external quantum efficiency of 25.4% in OLED.

Pseudomonas aeruginosa is an important chassis for production of polyhydroxyalkanoates (PHA) and rhamnolipids (RHL). Advances in the understanding of the biosynthesis metabolism of these biocompounds are crucial for increasing yield. 13C-Metabolic Flux Ratio Analysis (13C-MFA) is a technique to estimate in vivo metabolic fluxes ratios. PHA and RHL are essentially non-growth associated products of biotechnological interest and both contain hydroxyalkanoates (HAs), whose labeling patterns could be accessed by GC-MS. In this study, to reveal the relative contributions of the Entner-Doudoroff (ED) pathway and the non-oxidative Pentose Phosphate (PP) pathway to PHA and RHL production, 13C-MFA was performed in Pseudomonas aeruginosa LFM634 when supplied with labeled glucose. This bacterial strain lacks both functional EMP and the oxidative PP branch. Labeling patterns in HAs were measured. Experiments with [U-13C] glucose indicated a low flux though PP pathway. An optimal design of labeling experiment showed that [6-13C] glucose would be the best substrate to enable an estimation of the ED flux with high accuracy. Results of experiments performed with this isotope indicated that about two-thirds of glyceraldehyde 3-phosphate is recycled through a cyclic ED architecture, suggesting that P. aeruginosa utilizes that cycle to regulate the NADPH/Acetyl-CoA ratio for PHA and RHL biosynthesis.

The electromagnetic field (EMF) is a vital issue in research, but its use as an alternative technique for insect management is still in its beginnings. The study aimed to evaluate the effects of exposure to the electromagnetic field on the biochemical analysis and morphological characteristics in Culex pipiens. Therefore, the third instar larvae were exposed to EMF frequency (50 Hz) at different intensities (250, 500, 1000 mT) for 1 h during four successive days. After end exposure to EMF, the biochemical analysis, oxidative stress parameters, body weight, and morphological features were investigated. The results showed that larval body weight and total protein content were decreased significantly in all treated groups compared to controls. The total lipid content significantly decreased at 500 & 1000 mT exposure, while the treatment group exposed to EMF at 250 mT was not statistically different compared to control. At a high intensity of EMF 1000 mT all oxidative stress parameters; catalase (CAT) and Glutathione S-transferase (GST) activity and lipid peroxidation level (MDA) were decreased significantly compared to the control. On the other hand, at a low intensity (250 mT), CAT and GST activity was significantly increased, while MDA content was not statistically changed. Scanning electron microscopy showed that both 500 & 1000 mT caused distinct malformations to the larval body parts, mouthparts, thorax and abdomen with last abdominal structures. In conclusion, the results demonstrated that EMF exposure is a considerable stress factor that affects oxidative state and morphological features in mosquitoes and give hope that EMF will be used as an alternative method for Culex pipiens vector control.

Although the oxidative dehydrogenation of propane with CO2 (CO2-ODP) is a sustainable route for producing propylene with the tandem conversion of CO2 to the value-added CO, its industrialization is...

Oxidative stress inflicts mitochondrial dysfunction, which has been recognized as a key driver of intestinal diseases. Resveratrol (RSV) and its derivative pterostilbene (PTS) are natural antioxidants and exert a protective influence on intestinal health. However, the therapeutic effects and mechanisms of RSV and PTS on oxidative stress-induced mitochondrial dysfunction and intestinal injury remain unclear. The present study used porcine and cellular settings to compare the effects of RSV and PTS on mitochondrial redox homeostasis and function to alleviate oxidative stress-induced intestinal injury. Our results indicated that PTS was more potent than RSV in reducing oxidative stress, maintaining intestinal integrity, and preserving the mitochondrial function of diquat-challenged piglets. In the in vitro study, RSV and PTS protected against hydrogen peroxide (H2O2)-induced mitochondrial dysfunction in intestinal porcine enterocyte cell line (IPEC-J2) by facilitating mitochondrial biogenesis and increasing the activities of mitochondrial complexes. In addition, both RSV and PTS efficiently mitigated mitochondrial oxidative stress by increasing sirtuin 3 protein expression and the deacetylation of superoxide dismutase 2 and peroxiredoxin 3 in H2O2-exposed IPEC-J2 cells. Furthermore, RSV and PTS preserved mitochondrial membrane potential, which restrained the release of cytochrome C from mitochondria to the cytoplasm and caspase-3 activation and further reduced apoptotic rates in H2O2-exposed IPEC-J2 cells. Mechanistically, depletion of sirtuin 1 (SIRT1) abrogated RSV's and PTS's benefits against mitochondrial reactive oxygen species overproduction, mitochondrial dysfunction, and apoptosis in H2O2-exposed IPEC-J2 cells, suggesting that SIRT1 was required for RSV and PTS to protect against oxidative stress-induced intestinal injury. In conclusion, RSV and PTS improve oxidative stress-induced intestinal injury by regulating mitochondrial redox homeostasis and function via SIRT1 signaling pathway. In offering this protection, PTS is superior to RSV.

Hypothesis: A detailed quantitative description of the effects of antioxidants in inhibiting lipid peroxidation in oil-in-water emulsions can be achieved by determining the relationships between the rates of initiation of the lipid peroxidation reaction, the length of the induction period preceding the propagation step of the radical oxidation process and the effective antioxidant interfacial concentrations. Experiments : We successfully prepared and characterized a series of olive oil-in-water nanoemulsions and allowed them to spontaneously oxidize. Their oxidative stability was evaluated by carrying out in the presence, and absence, of antioxidants derived from gallic acid, by monitoring the formation of primary oxidation products with time, by determining the corresponding induction periods, and by determining the effective interfacial concentrations of the antioxidants in the intact emulsions. Findings: Results show that both, the length of the induction periods and the antioxidant interfacial concentrations change concomitantly, increasing with the hydrophobicity of the antioxidant up to a maximum at the octyl derivative; longer aliphatic chains decrease their efficiency. The ratio between the interfacial antioxidant concentration and the induction period remains constant independently of the antioxidant, demonstrating that the effective concentrations of antioxidant at the interface control their efficiencies in emulsions. Financiado para publicación en acceso aberto: Universidade de Vigo/CISUG Xunta de Galicia | Ref. ED431D 2017/18 Fundação para a Ciência e a Tecnologia | Ref. UID/QUI/50006/2013 Universidade de Vigo

A novel photocatalyzed trifluoromethylthio-trifluoromethylation of alkenes has been developed, using CF3SO2Na as both CF3 and SCF3 source. This photocatalyzed dual-oxidative strategy, which combine...

Heme is an essential nutritional, metabolic, and signaling molecule in living organisms. Pathogenic microbes extract heme from hosts to obtain metallonutrient, while heme fuels mitochondrial respiration and ATP generation in lung tumor cells. Here, we generated small heme-sequestering proteins (HeSPs) based on bacterial hemophores. These HeSPs contain neutral mutations in the heme-binding pocket and hybrid sequences from hemophores of different bacteria. We showed that HeSPs bind to heme and effectively extracted heme from hemoglobin. They strongly inhibited heme uptake and cell proliferation and induced apoptosis in non–small cell lung cancer (NSCLC) cells, while their effects on nontumorigenic cell lines representing normal lung cells were not significant. HeSPs strongly suppressed the growth of human NSCLC tumor xenografts in mice. HeSPs decreased oxygen consumption rates and ATP levels in tumor cells isolated from treated mice, while they did not affect liver and blood cell functions. IHC, along with data from Western blotting and functional assays, revealed that HeSPs reduced the levels of key proteins involved in heme uptake, as well as the consumption of major fuels for tumor cells, glucose, and glutamine. Further, we found that HeSPs reduced the levels of angiogenic and vascular markers, as well as vessel density in tumor tissues. Together, these results demonstrate that HeSPs act via multiple mechanisms, including the inhibition of oxidative phosphorylation, to suppress tumor growth and progression. Evidently, heme sequestration can be a powerful strategy for suppressing lung tumors and likely drug-resistant tumors that rely on oxidative phosphorylation for survival.

Boron nitride (BN) as an emerging and revolutionary metal-free catalyst has demonstrated great potential in various oxidative dehydrogenation reactions. However, traditional BN sheets always presen...

Antioxidants scavenge free radicals and may help prevent disease. However, due to poor stability, continuous intake is required. This study investigates the ability of cyclodextrin inclusion to improve the stability of the novel antioxidant edaravone. Kinetic models of cyclodextrin protection against edaravone oxidative decomposition were assessed and the data obtained was analyzed using Hanes–Woolf plots and Scatchard plots. In addition, complexation was analyzed using phase-solubility diagrams. The results show that cyclodextrin inclusion can control the oxidation rate of antioxidant molecules such as edaravone. This paper also demonstrates a substantial variation in the quantitative stability constant when calculated using different methods. This observation is relevant to determining complexation during the many and varied applications of cyclodextrins. The study establishes mechanisms to enhance the stability of antioxidants, which in turn may be useful to improve their bioavailability and may have translational implications in future.

Methods to detect and quantify disease biomarkers with high specificity and sensitivity in biological fluids play a key role in enabling clinical diagnosis, including point-of-care testing. Myeloperoxidase (MPO) is an emerging biomarker for the detection of inflammation, neurodegenerative diseases, and cardiovascular disease, where excess MPO can lead to oxidative damage to biomolecules in homeostatic systems. While numerous methods have been developed for MPO analysis, most techniques are challenging in clinical applications due to the lack of amplification methods, high cost, or other practical drawbacks. Enzyme-linked immunosorbent assays are currently used for the quantification of MPO in clinical practice, which is often limited by the availability of antibodies with high affinity and specificity and the significant nonspecific binding of antibodies to the analytical surface. In contrast, nucleic acid-based biosensors are of interest because of their simplicity, fast response time, low cost, high sensitivity, and low background signal, but detection targets are limited to nucleic acids and non-nucleic acid biomarkers are rare. Recent studies reveal that the modification of a genome in the form of phosphorothioate is specifically sensitive to the oxidative effects of the MPO/H2O2/Cl- system. We developed an oxidative cleavage-based three-dimensional DNA biosensor for rapid, ratiometric detection of HOCl and MPO in a "one-pot" method, which is simple, stable, sensitive, specific, and time-saving and does not require a complex reaction process, such as PCR and enzyme involvement. The constructed biosensor has also been successfully used for MPO detection in complex samples. This strategy is therefore of great value in disease diagnosis and biomedical research.

Ganoderic acid A (GAA) is a kind of lanostane-type triterpenoid isolated from Ganoderma lucidum. Imbalance of the Th17/Tregs axis exists in the progress of neuroinflammation of Alzheimer's disease (AD). In this study, the alleviating neuroinflammatory effect of GAA on d-galactose mice was studied from the aspect of regulating the imbalance of the Th17/Tregs axis. The Morris water maze test was used to evaluate the cognitive ability of AD mice. Flow cytometry was used to detect the percentages of IL-17A, IL-17F, IL-21, IL-22, and CD4+CD25+Foxp3+ in peripheral blood. Transmission electron microscopy was used to assess the cerebral mitochondrial ultrastructure. Metabolomic analysis based on gas chromatography-mass spectrometry was used to evaluate the mitochondrial dysfunction metabolism. Western blot analysis was used to detect the protein expressions of cytokines secreted by Th17 cells and Treg cells in the brain. As the results show, GAA has an alleviating neuroinflammatory effect on AD mice via regulating the imbalance of the Th17/Tregs axis. The potential mechanism was related to inhibition of the JAK/STAT signaling pathway induced by Th17 cells and enhancement of the mitochondrial oxidative phosphorylation by regulating Treg cells, thereby improving mitochondrial dysfunction of AD mice.

Objective: Chrysin and rutin are two dietary flavonoids lying in fruits or honey bee’s products. Their pharmacological properties include antioxidant, anti-inflammatory, anticancer, neuroprotection and immunomodulatory. In the current study, the potentiality of chrysin and rutin to protect human gingival fibroblasts against oxidative cell damage has been investigated in vitro. Method: Human gingival fibroblasts, passage 3, were concomitantly put in contact with the cytotoxic compounds and chrysin or rutin for 24 h at 37 °C, 5% CO2 atmosphere, and 96% humidity. The amount of viable cell after the incubated time was recorded by using the thiazolyl blue tetrazolium bromide (MTT) assay. Results: Chrysin in all tested concentration didn’t exhibit any cytoprotective effect against the tert-butyl hydroperoxide-induced oxidative cell damage. Moreover, chrysin in a low concentration (5 and 10 µg/mL) didn’t protect the fibroblasts against oxidative cell damage induced by the hydrogen peroxide. However, chrysin in a concentration of 20 µg/mL showed a significant cytoprotective activity in the hydrogen peroxide-induced cell damage (p < 0.05). Rutin in all tested concentrations protected fibroblasts against hydrogen peroxide and tert-butyl hydroperoxide-induced oxidative cell damage. The cytoprotective effect of rutin didn’t increase with the increase of the concentration when hydrogen peroxide is used to induce oxidative cell damage. However, rutin has protected cells against the tert-butyl hydroperoxide cytotoxicity in a concentration dependent manner. Conclusion: Given to the interesting cytoprotective activities exhibited by chrysin and rutin, further investigations to highlight their cytoprotective involved mechanisms are justified. Keywords: Chrysin, Cytoprotective, Fibroblasts, Rutin.

Aging, a time-dependent multifaceted process, affects both cell structure and function and involves oxidative stress as well as glycation. The present investigation focuses on the role of the band 3 protein (B3p), an anion exchanger essential to red cells homeostasis, in a d-galactose ( d-Gal)-induced aging model. Anion exchange capability, measured by the rate constant of SO₄²- uptake through B3p, levels of lipid peroxidation, oxidation of membrane sulfhydryl groups, B3p expression, methemoglobin, glycated hemoglobin (Hb), and the reduced glutathione/oxidized glutathione ratio were determined after exposure of human erythrocytes to 25, 35, 50, and 100 mmol/L d-Gal for 24 h. Our results show that: (i) in vitro application of d-Gal is useful to model early aging in human erythrocytes; (ii) assessment of B3p ion transport function is a sensitive tool to monitor aging development; (iii) d-Gal leads to Hb glycation and produces substantial changes on the endogenous antioxidant system; (iv) the impact of aging on B3p function proceeds through steps, first involving Hb glycation and then oxidative events at the membrane level. These findings offer a useful tool to understand the mechanisms of aging in human erythrocytes and propose B3p as a possible target for new therapeutic strategies to counteract age-related disturbances.

Synaptic activity imposes large energy demands that are met by local adenosine triphosphate (ATP) synthesis through glycolysis and mitochondrial oxidative phosphorylation. ATP drives action potentials, supports synapse assembly and remodelling, and fuels synaptic vesicle filling and recycling, thus sustaining synaptic transmission. Given their polarized morphological features — including long axons and extensive branching in their terminal regions — neurons face exceptional challenges in maintaining presynaptic energy homeostasis, particularly during intensive synaptic activity. Recent studies have started to uncover the mechanisms and signalling pathways involved in activity-dependent and energy-sensitive regulation of presynaptic energetics, or ‘synaptoenergetics’. These conceptual advances have established the energetic regulation of synaptic efficacy and plasticity as an exciting research field that is relevant to a range of neurological disorders associated with bioenergetic failure and synaptic dysfunction. Numerous energy-demanding cellular processes contribute to synaptic activity and function. Li and Sheng describe the mechanisms that regulate presynaptic energy supply to ensure that neurons can meet these demands and maintain their functions during periods of intensive synaptic activity.

A synthetic strategy for the formation of C(sp3)-N bonds, particularly through a copper-catalyzed oxidative cross-coupling, is rare. Herein, we report a novel synthetic approach for the preparation of tertiary sulfonamides via copper-catalyzed intra- and intermolecular oxidative C(sp3)-N cross-coupling reactions. This method allows the utilization of the readily available C(sp3)-based pinacol boronate as a substrate and the tolerance of a wide range of functional groups under mild reaction conditions. The success of this strategy relies on the unprecedented additive effects of silanol and NaIO4.

CERVOXY; International audience; Significance: Redox pioneer Helmut Sies attempted to explain reactive species' challenges faced by organelles, cells, tissues, and organs via three complementary definitions: (1) oxidative stress, i.e. the disturbance in the prooxidant-antioxidant defense balance in favor of the prooxidants, (2) oxidative eustress, the low physiological exposure to prooxidants, and (3) oxidative distress, the supraphysiological exposure to prooxidants. Recent Advances: Identification, concentration and interactions are the most important elements to improve our understanding of reactive species in physiology and pathology. In this context, the reactive species interactome (RSI) is a new multilevel redox regulatory system that identifies reactive species families, reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS), and integrates their interactions with their downstream biological targets.Critical issues: We propose a united view to fully combine reactive species identification, oxidative eustress and distress, and the RSI system. In this view, we also propose including the forgotten reactive carbonyl species (RCS), an increasingly rediscovered reactive species family related to the other reactive families, and key enzymes within the RSI. We focus on brain physiology and pathology to demonstrate why this united view should be considered.Future directions: More studies are needed for an improved understanding of the contributions of reactive species through their identification, concentration, and interactions, including in the brain. Appreciating the reactive species interactome in its entirety should unveil new molecular players and mechanisms in physiology and pathology in the brain and elsewhere.

Metal-free boron-based catalytic systems are growing to be promising choices in the oxidative dehydrogenation (ODH) of light alkanes to olefins. However, the ambiguity in the understanding of the m...

A novel P,N-bidentate ligand-assisted gold-catalyzed oxidative amination of β-amino-ynones has been developed, allowing the simple and efficient construction of various quaternary ammonium-olate salts in good to excellent yields. These unprecedented quaternary ammonium-olate salts can be isolated and purified via simple suction filtration. The broad substrate scope, easy purification, easy further transformation, and mild conditions make it a viable alternative for the synthesis of various quaternary ammonium-olate salts.

Background. Oxidative stress is an important mechanism of cerebral ischemia-reperfusion injury. Ferroptosis caused by iron overload after cerebral ischemia-reperfusion is considered a common cause of oxidative stress. Many recent studies have shown that electroacupuncture (EA) can regulate the expression of inflammatory factors, and the use of electroacupuncture preconditioning can produce a protective effect, which can reduce injury after cerebral ischemia and reperfusion. We aimed to assess whether EA could be used to reduce oxidative stress. Methods. The oxidative stress level of rats during the acute phase of cerebral ischemia and reperfusion was assessed with and without preconditioning with EA. Molecular biology methods were used to detect iron metabolism and oxidative stress-related proteins. Results. Rats that had EA preconditioning had lower infarct volumes than rats in the control group. Furthermore, western blot analysis showed that the expression of iron metabolism-related protein FPN-1 was higher in the intervention group than in the model group after reperfusion. In this regard, further investigation also demonstrated higher expression of glutathione and glutathione peroxidase-4, and lower reactive oxygen species values in the brain tissue of the EA group were compared with those of the control group rats. Conclusions. Electroacupuncture preconditioning can reduce oxidative stress after cerebral ischemia-reperfusion by regulating iron overload.

In this work, we synthesized a series of new 9,10-dihydro-2H,8H-chromeno[8,7e][1,3]oxazine-2-on derivatives which incorporate isobornylcoumarin and 1,3-oxazine moieties. A structure-antioxidant activity relationship was analyzed. A comparative evaluation of their radical scavenging activity, antioxidant and membrane-protective properties was carried out in test with DPPH, as well as on the models of Fe2+ /ascorbate-initiated lipid peroxidation and oxidative hemolysis of mammalian red blood cells. The results suggest that all the obtained coumarin[1,3]oxazine derivatives of 7-hydroxy-6-isobornyl-4-methylcoumarin are capable of exhibiting antioxidant activity in various model systems. Compound 7 with a phenyl fragment, combining high radical scavenging activity and the ability to inhibit Fe2+ /ascorbate-initiated peroxidation of animal lipids in a heterogeneous environment, also proved to be the most effective membrane protector and antioxidant in the model of H2 O2 -induced erythrocyte hemolysis.

Tibialis anterior muscles of 45-week-old female obese Zucker rats with defective leptin receptor and non-insulin dependent diabetes mellitus (NIDDM) showed a significative atrophy compared to lean muscles, based on histochemical-stained section’s measurements in the sequence: oxidative slow twitch (SO, type I) < oxidative fast twitch (FOG, type IIa) < fast glycolytic (FG, type IIb). Both oxidative fiber’s outskirts resembled ‘ragged’ fibers and, in these zones, ultrastructure revealed small clusters of endoplasm-like reticulum filled with unidentified electron contrasted compounds, contiguous and continuous with adjacent mitochondria envelope. The linings appeared crenated stabbed by circular patterns resembling those found of ceramides. The same fibers contained scattered degraded mitochondria that tethered electron contrasted droplets favoring larger depots while mitoptosis were widespread in FG fibers. Based on other interdisciplinary investigations on the lipid depots of diabetes 2 muscles made us to propose these accumulated contrasted contents to be made of peculiar lipids, including acyl-ceramides, as those were only found while diabetes 2 progresses in aging obese rats. These could interfere in NIDDM with mitochondrial oxidative energetic demands and muscle functions.

Alzheimer's disease (AD) is a neurodegenerative disorder which leads to mental deterioration due to aberrant accretion of misfolded proteins in the brain. According to mitochondrial cascade hypothesis, mitochondrial dysfunction is majorly involved in the pathogenesis of AD. Many drugs targeting mitochondria to treat and prevent AD are in different phases of clinical trials for the evaluation of safety and efficacy as mitochondria are involved in various cellular and neuronal functions. Mitochondrial dynamics is regulated by fission and fusion processes mediated by dynamin-related protein (Drp1). Inner membrane fusion takes place by OPA1 and outer membrane fusion is facilitated by mitofusin1 and mitofusin2 (Mfn1/2). Excessive calcium release also impairs mitochondrial functions; to overcome this, calcium channel blockers like nilvadipine are used. Another process acting as a regulator of mitochondrial function is mitophagy which is involved in the removal of damaged and non-functional mitochondria however this process is also altered in AD due to mutations in Presenilin1 (PS1) and Amyloid Precursor Protein (APP) gene. Mitochondrial dynamics is altered in AD which led to the discovery of various fission protein (like Drp1) inhibitors and drugs that promote fusion. Modulations in AMPK, SIRT1 and Akt pathways can also come out to be better therapeutic strategies as these pathways regulate functions of mitochondria. Oxidative phosphorylation is major generator of Reactive Oxygen Species (ROS) leading to mitochondrial damage; therefore reduction in production of ROS by using antioxidants like MitoQ, Curcumin and Vitamin Eis quiteeffective.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serious complication after long-term or excess administration of clinical glucocorticoids intervention, and the pathogenic mechanisms underlying have not been clarified yet. Oxidative stress is considered as a major cause of bone homeostasis disorder. This study is aimed to explore the potential relevance between SIRT3 and GIONFH, as well as the effect of resveratrol, which has been reported for its role in SIRT3 activation, on dexamethasone-induced oxidative stress and mitochondrial compromise in bone marrow stem cells (BMSCs). In this study, our data showed that SIRT3 level was declined in GIONFH rat femoral head, corresponding to a resultant decrease of SIRT3 expression in dexamethasone-treated BMSCs in vitro. We also found that dexamethasone could result in oxidative injury in BMSCs, and resveratrol treatment reduced this deleterious effect via a SIRT3-dependent manner. Moreover, our results demonstrated that rewarding effect of resveratrol on BMSCs osteogenic differentiation was via activation of AMPK/PGC-1α/SIRT3 axis. Meanwhile, resveratrol administration prevented the occurrence of GIONFH, enhanced SIRT3 expression and reduced oxidative level in GIONFH model rats. Therefore, our study provides basic evidence that SIRT3 may be a promising therapeutic target for GIONFH treatment and resveratrol could be an ideal agent for clinical uses.