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Chromosome damage combined with defective recombinase activity renders cells inviable, owing to deficient double-strand break repair. Despite this, recA polA cells grow well under either DNA damage response (SOS) conditions or catalase medium supplementation. Catalase treatments reduce intracellular reactive oxygen species (ROS) levels, suggesting that recA polA cells are susceptible to not only chronic chromosome damage but also ROS. In this study, we used a reducing agent, vitamin C, to confirm whether cell growth could be improved. Vitamin C reduced ROS levels and rescued colony formation in recAts polA cells under restrictive temperatures in the presence of hslO, the gene encoding a redox molecular chaperone. Subsequently, we investigated the role of hslO in the cell growth failure of recAts polA cells. The effects of vitamin C were observed in hslO+ cells; simultaneously, cells converged along several ploidies likely through a completion of replication, with the addition of vitamin C at restrictive temperatures. These results suggest that HslO could manage oxidative stress to an acceptable level, allowing for cell division as well as rescuing cell growth. Overall, ROS may regulate several processes, from damage response to cell division. Our results provide a basis for understanding the unsolved regulatory interplay of cellular processes.

Parkinson’s disease (PD) occurs in approximately 1% of the population over 65 years of age and has become increasingly more common with advances in age. The number of individuals older than 60 years has been increasing in modern societies, as well as life expectancy in developing countries; therefore, PD may pose an impact on the economic, social, and health structures of these countries. Oxidative stress is highlighted as an important factor in the genesis of PD, involving several enzymes and signaling molecules in the underlying mechanisms of the disease. This review presents updated data on the involvement of oxidative stress in the disease, as well as the use of antioxidant supplements in its therapy.

Se is beneficial to plants’ growth and it is an essential mineral for animals and humans. However, relatively little is known about the relationship between nano-Se concentrations and plant antioxi...

To study the pharmacological mechanism of Guanxin II formula (冠心II号方) for treatment of coronary heart disease (CHD). A network pharmacology-based method was utilized. First candidate compounds, targets of GX II were collected using PharmMapper, BATMAN-TCM, DrugBank and SwissTargetPrediction, and targets on CHD were mined from GeneCards, DisGenet, DrugBank and GEO. Afterwards, the big hub compounds and targets were chosen in the candidate compounds-direct therapeutic targets on the CHD (C-T) network and the direct therapeutic targets on the CHD (T-D) network. Furthermore, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to identify the enriched terms. Finally, a molecular docking simulation strategy was adopted to verify the binding capacity between the big hub compounds and big hub targets on CHD. First, 114 candidate compounds were selected with the following criteria: OB⩾30%, DL⩾0.18, and HL ⩾4 h. Then, 1,035 targets of GX II were gathered, while 928 targets on CHD were collected. Afterwards, 196 common targets of compound targets and therapeutic targets on CHD were defined as direct therapeutic targets acting on CHD. In addition, the contribution index (CI) in the C-T network was calculated, and 4 centrality properties, including degree, betweenness, closeness and coreness, in the T-D network, 4 big hub compounds, and 6 big hub targets were eventually chosen. Furthermore, the GO and KEGG analysis indicated that GX II acted on CHD by regulating the reactive oxygen species metabolism, steroid metabolism, lipid metabolism, inflammatory response, proliferation, differentiation and apoptosis. The docking results manifested excellent binding capacity between the 4 big hub compounds and 6 big hub targets on CHD. This network pharmacology-based exploration revealed that GX II might prevent and inhibit the primary pathological processes of CHD.

Tomato (Solanum lycopersicum L.) fruit cracking is a serious economic problem, affecting fruit quality and yield. During abiotic stress, the imbalance of reactive oxygen species (ROS) metabolism ca...

Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment option for cancers and other diseases. The key factor that determines the effectiveness of PDT is the photosensitizers (PSs). Upon light irradiation, the PSs would be activated, produce reactive oxygen species (ROS), and induce cell death. One of the challenges is that traditional PSs adopt a large flat disc-like structure, which tend to interact with the adjacent molecules through strong π-π stacking that reduces their ROS generation ability. Aggregation-induced emission (AIE) molecules with a twisted configuration to suppress strong intermolecular interactions represent a new class of PSs for image-guided PDT. In this Miniperspective, we summarize the recent progress on the design rationale of AIE-PSs and the strategies to achieve desirable theranostic applications in cancers. Subsequently, approaches of combining AIE-PS with other imaging and treatment modalities, challenges, and future directions are addressed.

Organo-seleno compounds (org-Se) have been widely used in antitumor, antiviral, and antiinflammatory therapy; antioxidation and other biological fields. As such, they have made an important contribution to overcoming various kinds of diseases, and researchers are increasingly attracted to org-Se's synthesis and functional design. This review is mainly focused on the design and synthesis of various kinds of org-Se, followed by their anticancer mechanisms such as the mitochondria mediated pathway induced by ROS, death receptor mediated pathways involving p53 phosphorylation, and the activation of the AMPK pathway to promote apoptosis. Org-Se also serves as a sensitizer in chemotherapy and radiotherapy, and an antagonist against the cytotoxic effects induced by chemotherapeutic agents. Finally, we will summarize the development of cancer-targeted org-Se containing complexes, and nanotechnology-based org-Se for anticancer application. This review could provide information for the future design of chemically innovative org-Se with anticancer potential, and shed light on the discovery of nanomaterial-based pharmaceuticals to improve drug development and formation.

Because of their highly reactive nature and potentially toxic characteristic, reactive oxygen species (ROS) have had a bad reputation for years. However, under certain conditions, ROS generation has shown positive outcomes. It is ROS imbalance that causes toxic effects. ROS play an important role in physiological processes such as cell signaling, senescence, inflammation, and the immune response to infection. An increasing number of studies highlight the importance of ROS for the inflammatory response, whether sterile or due to infection or cancer. The purpose of this paper is to present evidence of the essential role of ROS in the inflammatory response.

Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 μg mL-1 was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π-π and CS interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.

The association between occupational radiation exposure and endothelium-dependent vasodilation (EDV) remains unclear. This study evaluated the association between radiation exposure and EDV among fluoroscopy-guided interventional procedure specialists and explored the possible mechanisms.Brachial flow-mediated dilation was compared in 21 interventional cardiologists (the radiation group) and 15 noninterventional cardiologists (the nonradiation group). Animal radiation experiments were also performed to observe the impact of radiation on EDV.Flow-mediated dilation in both the left (radiation group, 3.63% vs. nonradiation group, 6.77%; P.001) and right brachial arteries (5.36% vs. 7.33%, respectively; P = .04) and serum nitric oxide (NO) level (343.69 vs. 427.09 μmol/L, respectively; P = .02) were significantly reduced in the radiation group compared to those in the nonradiation group. EDV was significantly impaired in acetylcholine concentrations of 3 × 10Radiation exposure can lead to impairment of flow-mediated vasodilation in human or EDV in mice. In mice acutely exposed to radiation, folic acid alleviated radiation-induced EDV impairment by possible reduction of reactive oxidative species.

The data on the neoteny (prolongation of youth and retardation of aging) in naked mole rat (Heterocephalus glaber) and Homo sapiens are summarized. Fifty-eight neotenic traits have been described by now in the naked mole rat at the organismal, tissue, cellular, and metabolism levels. Among them, there are traits that increase the lifespan, including mild depolarization of mitochondria that prevents generation by these organelles of reactive oxygen species known to strongly promote aging. Mild mitochondrial depolarization disappears with age in short-lived mammals (mouse Mus musculus) much faster than in long-lived mammals (e.g., naked mole rats and bats). The development of neoteny in naked mole rats has been due to the social organization. These animals live in subterranean colonies, where sexual reproduction is monopolized by the queen and one or several males who are defended and provided with nutrition by numerous subordinates. Humans have achieved a gradual increase in the lifespan first due to neoteny, and then to the technical progress, which can be observed by comparing the lifespan curves of chimpanzees, hunter-gatherers of the Paraguayan Ache tribe, and residents of Sweden from the XVII century to the present day. Significantly different rates of neoteny and technical progress make it possible to discriminate between the contributions of these two longevity mechanisms.

Rosa roxburghii fruit were used as research objects to study the effects of different concentrations of benzothiazole (BTH) treatment on quality parameters, reactive oxygen species (ROS) metabolism, and the phenylpropanoid pathway during storage at 4°C for 14days. Results showed that BTH effectively delayed senescence with lower decay incidence, weight loss, and lipid peroxidation level and maintained the quality with higher contents of total soluble solid (TSS) content, titratable acidity (TA) in R. roxburghii fruit. Moreover, BTH increased hydrogen peroxide (H2O2) content, superoxide anion (O2•−) production rate, and the activities and expression of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione (GSH) reductase (GR), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and peroxidase (POD), and the contents of GSH and ascorbic acid (AsA), but reduced the oxidized GSH (GSSG) content. In addition, the activities and gene expression of phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL) and the concentrations of flavonoids, total phenols, and lignin were significantly elevated by BTH. These findings imply that BTH can delay senescence and maintain the quality of R. roxburghii fruit by modulating ROS metabolism and the phenylpropanoid pathway under low-temperature conditions.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Rosa roxburghii fruit were used as research objects to study the effects of different concentrations of benzothiazole (BTH) treatment on quality parameters, reactive oxygen species (ROS) metabolism, and the phenylpropanoid pathway during storage at 4°C for 14days. Results showed that BTH effectively delayed senescence with lower decay incidence, weight loss, and lipid peroxidation level and maintained the quality with higher contents of total soluble solid (TSS) content, titratable acidity (TA) in R. roxburghii fruit. Moreover, BTH increased hydrogen peroxide (H2O2) content, superoxide anion (O2•−) production rate, and the activities and expression of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione (GSH) reductase (GR), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and peroxidase (POD), and the contents of GSH and ascorbic acid (AsA), but reduced the oxidized GSH (GSSG) content. In addition, the activities and gene expression of phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL) and the concentrations of flavonoids, total phenols, and lignin were significantly elevated by BTH. These findings imply that BTH can delay senescence and maintain the quality of R. roxburghii fruit by modulating ROS metabolism and the phenylpropanoid pathway under low-temperature conditions.

Herein, a light-activatable photosensitizer based on a diarylethene derivative, DAE-TPE, was developed for photodynamic therapy. Upon UV exposure, the "opened" form (OF) of DAE-TPE NPs was converted to the "closed" form (CF), and photosensitization was activated. The CF of DAE-TPE NPs exhibited sufficient photodynamic therapy effects upon HeLa cells.

Peroxisomes, essential subcellular organelles that fulfill important functions in lipid and reactive oxygen species metabolism, have recently emerged as key players during viral infections. Their importance for the establishment of the cellular antiviral response has been highlighted by numerous reports of specific evasion of peroxisome-dependent signaling by different viruses. Recent data demonstrate that peroxisomes also assume important proviral functions. Here, we review and discuss the recent advances in the study of the diverse roles of peroxisomes during viral infections, from animal to plant viruses, and from basic to translational perspectives. We further discuss the future development of this emerging area and propose that peroxisome-related mechanisms represent a promising target for the development of novel antiviral strategies.

In theory, scientific discovery follows the path of putting forward a hypothesis, testing it and either accepting it as a theory or discarding it based on the outcome of testing. As it often happen...

Lipid peroxidation underlies the mechanism of oxidative cell death now known as ferroptosis. This modality, distinct from other forms of cell death, has been intensely researched in recent years owing to its relevance in both degenerative disease and cancer. The demonstration that it can be modulated by small molecules in multiple pathophysiological contexts offers exciting opportunities for novel pharmacological interventions. Herein, we introduce the salient features of lipid peroxidation, how it can be modulated by small molecules and what principal aspects require urgent investigation by researchers in the field. The central role of non-enzymatic reactions in the execution of ferroptosis will be emphasized, as these processes have hitherto not been generally considered 'druggable'. Moreover, we provide a critical perspective on the biochemical mechanisms that contribute to cell vulnerability to ferroptosis and discuss how they can be exploited in the design of novel therapeutics.

Two novel C19 terpenoids (1, 2) with an unprecedented carbon skeleton (A) were isolated from a Stelletta sp. sponge collected from Vietnamese waters. Their structures and absolute configurations were established by extensive NMR, MS, and ECD analyses together with quantum chemical modeling and biogenetic considerations. The probable pathways of biogenesis of 1 and 2 from isomalabaricane triterpenoids are discussed. Compounds 1 and 2 significantly increase the production of reactive oxygen species in murine peritoneal macrophages.

Key Points Ponatinib therapy heightens arterial thrombosis and platelet reactivity. Concurrent pioglitazone treatment reverses heightened thrombosis risk and platelet reactivity induced by ponatinib.

Measurement of the levels of the derivatives of reactive oxygen metabolites (d-ROMs) and of the biological antioxidant potential (BAP) enables simultaneous assessment of oxidation degree and antioxidant capacity, using the same sample and testing equipment. At present, reference values of healthy adults are clarified, but the reference value of healthy children is unknown. This study was undertaken to clarify the age-related changes and the reference values of d-ROMs and BAP in healthy children.The study population consisted of 77 children, ranging in age from 2 to 15 years, in normal mental and physical health as examined by a pediatrician, and seven healthy adult volunteers. Serum samples were obtained from the subjects for assay. Using these samples, d-ROMs and BAP values were measured, and the relationship with age was analyzed.The d-ROMs level decreased as the age increased, while the BAP showed no correlation with the age. The d-ROMs level was significantly higher in 2-6 years group than in 7-11 years group, 12-15 years group, or healthy adults group. The BAP/d-ROMs ratio, an index of antioxidant capacity, increased significantly with higher age.This study was carried out for the first time in healthy children in oxidative stress assessment using d-ROMs and BAP. In the infancy 2-6 years, the d-ROMs value was significantly higher and the BAP/d-ROMs ratio was significantly lower. From this, it was suggested that age should be considered when performing oxidative stress assessment using d-ROMs and BAP in children.

Nanozymes are nanomaterials with intrinsic enzyme-like characteristics that have been booming over the past decade because of their capability to address the limitations of natural enzymes such as low stability, high cost, and difficult storage. Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanozymes hold promise to serve as direct surrogates of traditional enzymes by mimicking and further engineering the active centers of natural enzymes. In 2007, we reported the first evidence that Fe3O4 nanoparticles (NPs) have intrinsic peroxidase-mimicking activity, and since that time, hundreds of nanomaterials have been found to mimic the catalytic activity of peroxidase, oxidase, catalase, haloperoxidase, glutathione peroxidase, uricase, methane monooxygenase, hydrolase, and superoxide dismutase. Uniquely, a broad variety of nanomaterials have been reported to simultaneously exhibit dual- or multienzyme mimetic activity. For example, Fe3O4 NPs show pH-dependent peroxidase-like and catalase-like activities; Prussian blue NPs simultaneously possess peroxidase-, catalase-, and superoxide dismutase-like activity; and Mn3O4 NPs mimic all three cellular antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Taking advantage of the physiochemical properties of nanomaterials, nanozymes have shown a broad range of applications from in vitro detection to replacing specific enzymes in living systems. With the emergence of the new concept of "nanozymology", nanozymes have now become an emerging new field connecting nanotechnology and biology. Since the landmark paper on nanozymes was published in 2007, we have extensively explored their catalytic mechanism, established the corresponding standards to quantitatively determine their catalytic activities, and opened up a broad range of applications from biological detection and environmental monitoring to disease diagnosis and biomedicine development. Here we mainly focus on our progress in the systematic design and construction of functionally specific nanozymes, the standardization of nanozyme research, and the exploration of their applications for replacing natural enzymes in living systems. We also show that, by combining the unique physicochemical properties and enzyme-like catalytic activities, nanozymes can offer a variety of multifunctional platforms with a broad of applications from in vitro detection to in vivo monitoring and therapy. For instance, targeting antibody-conjugated ferromagnetic nanozymes simultaneously provide three functions: target capture, magnetic separation, and nanozyme color development for target detection. We finally will address the prospect of nanozyme research to become "nanozymology". We expect that nanozymes with unique physicochemical properties and intrinsic enzyme-mimicking catalytic properties will attract broad interest in both fundamental research and practical applications and offer new opportunities for traditional enzymology.

Dear Editor, The measurement of malondialdehyde (MDA) content has long been used as a lipid peroxidation marker in studies related to oxidative stress and redox signaling, particularly in those studies focused on plant responses to abiotic and biotic stresses. A search for “malondialdehyde” and

Polyelectrolytes play an important role in both natural biological systems and human society, and their synthesis, functional exploration, and profound application are thus essential for biomimicry and creating new materials. In this study, we developed an efficient synthetic methodology for in situ generation of azonia-containing polyelectrolytes in a one-pot manner by using readily accessible nonionic reactant in the presence of commercially available cheap ionic species. The resulting polyelectrolytes are emissive in the solid state and can readily form luminescent photopatterns with different colors. The azonia-containing polyelectrolytes possess extraordinary potency of reactive oxygen species (ROS) generation, enabling them to impressively kill methicillin-resistant Staphylococcus aureus (MRSA), a drug resistant superbug, both in vitro and in vivo.

Reactive oxygen species (ROS) play an essential role in regulating various physiological functions of living organisms. The intrinsic biochemical properties of ROS, which underlie the mechanisms necessary for the growth, fitness, or aging of living organisms, have been driving researchers to take full advantage of these active chemical species for contributing to medical advances. Thanks to the remarkable advances in nanotechnology, great varieties of nanomaterials with unique ROS-regulating properties have been explored to guide the temporospatial dynamic behaviors of ROS in biological milieu, which contributes to the emergence of a new-generation therapeutic methodology, i.e., nanomaterial-guided in vivo ROS evolution for therapy. The interdependent relationship between ROS and their corresponding chemistry, biology, and nanotherapy leads us to propose the concept of "ROS science", which is believed to be an emerging scientific discipline that studies the chemical mechanisms, biological effects, and nanotherapeutic applications of ROS. In this review, state-of-art studies concerning recent progresses on ROS-based nanotherapies have been summarized in detail, with an emphasis on underlying material chemistry of nanomaterials by which ROS are generated or scavenged for improved therapeutic outcomes. Furthermore, key scientific issues in the evolution of ROS-based cross-disciplinary fields have also been discussed, aiming to unlock the innate powers of ROS for optimized therapeutic efficacies. We expect that our demonstration on this evolving field will be beneficial to the further development of ROS-based fundamental researches and clinical applications.

Carbon dots (C-Dots), defined by characteristic sizes of

Nitric oxide (NO) is a small free radical with critical signaling roles in physiology and pathophysiology. The generation of sufficient NO levels to regulate the resistance of the blood vessels and hence the maintenance of adequate blood flow is critical to the healthy performance of the vasculature. A novel paradigm indicates that classical NO synthesis by dedicated NO synthases is supplemented by nitrite reduction pathways under hypoxia. At the same time, reactive oxygen species (ROS), which include superoxide and hydrogen peroxide, are produced in the vascular system for signaling purposes, as effectors of the immune response, or as byproducts of cellular metabolism. NO and ROS can be generated by distinct enzymes or by the same enzyme through alternate reduction and oxidation processes. The latter oxidoreductase systems include NO synthases, molybdopterin enzymes, and hemoglobins, which can form superoxide by reduction of molecular oxygen or NO by reduction of inorganic nitrite. Enzymatic uncoupling, changes in oxygen tension, and the concentration of coenzymes and reductants can modulate the NO/ROS production from these oxidoreductases and determine the redox balance in health and disease. The dysregulation of the mechanisms involved in the generation of NO and ROS is an important cause of cardiovascular disease and target for therapy. In this review we will present the biology of NO and ROS in the cardiovascular system, with special emphasis on their routes of formation and regulation, as well as the therapeutic challenges and opportunities for the management of NO and ROS in cardiovascular disease.

Due to the abuse of antibiotics and the tendency of bacteria to form protective biofilms, the design and development of new efficient agents that can eliminate bacteria and biofilms are still highly desired but remain a great challenge; on the other hand, natural enzymes with unique catalytic characteristics can cause an irreversible damage to the bacteria without inducing drug-resistance in the bacteria. However, the intrinsic drawbacks, such as insufficient stability and high purification cost, of enzymes significantly limit their antimicrobial applications. Therefore, significant research efforts have been devoted towards the development of quality-equivalent or even superior enzyme substitutes with low cost and high stability. In this regard, nanomaterials with extraordinary enzyme-mimetic catalytic activities (termed as nanozymes) are considered as suitable candidates. To date, nanozymes have been proved to be promising materials for combating bacteria and biofilms under mild conditions. In this review, we have summarized the recent progress of nanozymes in this highly active field. The antibacterial mechanisms of nanozymes and the roles of their sizes, morphologies, compositions, surface modifications and microenvironment on their overall performance have been discussed. Moreover, the current challenges and prospects in this research area have been discussed. We believe that nanozymes with unique features and functions can provide a wealth of opportunities via their clinical and industrial applications.

Cholesterol (CHOL) is an indispensable component of liposomes. Incorporation of 7-dehydrocholesterol (7-DHC) instead of CHOL can efficiently enhance the anticancer activity of photosensitizer-encapsulated liposomes upon irradiation, yielding an IC50 value about half of that of CHOL-based controls. The photo-oxidation of 7-DHC into its endoperoxide form by singlet oxygen may account for the enhanced therapeutic effect, realizing an efficient combination of photodynamic therapy (PDT) and photoactivated chemotherapy.

A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice.

A nuclear-targeted titanium dioxide radiosensitizer was developed to regulate the cell cycle and enhance the radiation effect.

ZusammenfassungVerschiedene Faktoren sind in der Pathogenese der alkoholischen Lebererkrankung (ALE) und der alkoholvermittelten Karzinogenese beteiligt. Neben genetischen, epigenetischen und immunologischen Mechanismen spielen die toxische Wirkung von Acetaldehyd, oxidativer Stress und zytokinvermittelte Entzündungen eine wesentliche Rolle. Oxidativer Stress mit der Generierung von reaktiven Sauerstoffspezies (ROS) entsteht entweder in der Entzündung (alkoholische Hepatitis) oder bei der Alkoholoxidation via Cytochrom P4502E1 (CYP2E1). CYP2E1 wird durch Alkohol induziert, oxidiert Äthanol zu Acetaldehyd und generiert dabei ROS. ROS führt unter anderem zu Proteinschädigung, Fibrogenese und DNA-Mutationen. Weiterhin resultiert die CYP2E1-Induktion in einer gesteigerten Prokarzinogenaktivierung und einem verstärkten Abbau von Retinol und Retinsäure, einem Faktor, der für eine geordnete Zelldifferenzierung und Zellproliferation verantwortlich ist. Eine Hemmung von CYP2E1 führt zu einer Verbesserung der ALE und zu einer Hemmung der chemisch induzierten Karzinogenese im Tierexperiment. Beim Menschen wird CYP2E1 bereits bei 40 Gramm Alkohol pro Tag innerhalb einer Woche induziert, jedoch gibt es signifikante interindividuelle Unterschiede. Der Mechanismus dafür ist unklar. Bei Patienten mit ALE korreliert CYP2E1 mit dem Ausmaß von hochkarzinogenen Etheno-DNA-Addukten in Leber und Ösophagus und mit der Schwere der Leberfibrose. Erste Ergebnisse zu einer Hemmung von CYP2E1 durch Chlormethiazol, einem spezifischen CYP2E1-Hemmer, bei Patienten mit ALE sind in Kürze zu erwarten.

COVID-19 disease has put life of people in stress worldwide from many aspects. Since the virus has mutated in absolutely short period of time the challenge to find a suitable vaccine has become harder. Infection to COVID-19, especially at severe life threatening states is highly dependent on the strength of the host immune system. This system is partially dependent on the balance between oxidative stress and antioxidant. Besides, this virus still has unknown mechanism of action companied by a probable commune period. From another hand, some reactive oxygen species (ROS) levels can be helpful on the state determination of the disease. Thus it could be possible to use modern bioanalytical techniques for their detection and determination, which could indicate the disease state at the golden time window since they have the potential to show whether specific DNA, RNA, enzymes and proteins are affected. This also could be used as a preclude study or a reliable pathway to define the best optimized time of cure beside effective medical actions. Herein, some ROS and their relation with SARS-CoV-2 virus have been considered. In addition, modern bioelectroanalytical techniques on this approach from quantitative and qualitative points of view have been reviewed., Graphical abstract Unlabelled Image

Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.

Elevated levels of reactive oxygen species (ROS) have commonly been implicated in a variety of diseases, including cancer, inflammation, and neurodegenerative diseases. In light of significant differences in ROS levels between the nonpathogenic and pathological tissues, an increasing number of ROS-responsive prodrugs, probes, and theranostic prodrugs have been developed for the targeted treatment and precise diagnosis of ROS-related diseases. This review will summarize and provide insight into recent advances in ROS-responsive prodrugs, fluorescent probes, and theranostic prodrugs, with applications to different ROS-related diseases and various subcellular organelle-targetable and disease-targetable features. The ROS-responsive moieties, the self-immolative linkers, and the typical activation mechanism for the ROS-responsive release are also summarized and discussed.

Bacterial infection is a major global threat to human health and currently one of the leading causes of death worldwide. The development of probes for rapid diagnosis of bacteria with desired sensitivity and selectivity along with antibacterial activity against multidrug-resistant (MDR) bacteria has remained a great challenge. Whilst the traditional methods such as cell culture and colony counting, polymerase chain reaction and immunoassays are used for bacterial infection detection, these are time consuming, laborious and require a skilled operator. On the other hand, the rapid emergence of MDR bacteria is also posing another serious public health threat. Hence, it is an utmost urgency to develop novel therapeutics and rapid diagnostic agents for tackling MDR bacteria. Over the last few years, significant progress has been made towards the development of metal-based aggregation-induced emission luminogens (AIEgens) for bacterial management. These AIEgen materials offer potential applications for simultaneous detection and image-guided elimination of bacteria for the treatment of bacterial infections. In this Feature Article, we have highlighted the recent progress in the development of metal-based AIEgens for detection, discrimination and decimation of bacteria. In addition, the potential challenges in developing antibacterial agents and several future perspectives of metal-based AIEgens in this field have also been discussed.

Photosensitizers are photosensitive molecules utilized in clinical and non-clinical applications by taking advantage of light-mediated reactive oxygen generation, which triggers local and systemic cellular toxicity. Photosensitizers are used for diverse biological applications such as spatio-temporal inactivation of a protein in a living system by chromophore-assisted light inactivation, localized cell photoablation, photodynamic and immuno-photodynamic therapy, and correlative light-electron microscopy imaging. Substantial efforts have been made to develop several genetically encoded, chemically synthesized, and nanotechnologically driven photosensitizers for successful implementation in redox biology applications. Genetically encoded photosensitizers (GEPS) or reactive oxygen species (ROS) generating proteins have the advantage of using them in the living system since they can be manipulated by genetic engineering with a variety of target-specific genes for the precise spatio-temporal control of ROS generation. The GEPS variety is limited but is expanding with a variety of newly emerging GEPS proteins. Apart from GEPS, a large variety of chemically- and nanotechnologically-empowered photosensitizers have been developed with a major focus on photodynamic therapy-based cancer treatment alone or in combination with pre-existing treatment methods. Recently, immuno-photodynamic therapy has emerged as an effective cancer treatment method using smartly designed photosensitizers to initiate and engage the patient's immune system so as to empower the photosensitizing effect. In this review, we have discussed various types of photosensitizers, their clinical and non-clinical applications, and implementation toward intelligent efficacy, ROS efficiency, and target specificity in biological systems.

Reactive oxygen species (ROS)-responsive prodrug nanoplatforms may not work efficiently due to insufficient ROS concentrations, so therapeutic polymersomes of a metallisable triamine-centered iminoboronate-functionalized amphiphilic starlike prodrug (N3-(OEG-IBCAPE)4) are prepared to show a Cu(ii)-mediated Fenton reaction-enhanced ROS response.

The specific monitoring of physiological highly reactive oxygen species (hROS) using fluorescent gold nanoclusters (AuNCs) remains a challenge for scientists. Herein, SLB-AuNC was first synthesized via an ecofriendly one-pot method using starch as a template, l-3,4-dihydroxyphenylalanine (l-DOPA) as a reducing and a capping agent, and boric acid as a protecting agent for the catechol moiety of l-DOPA. The ingenious introduction of starch and boric acid enhanced the dispersibility, quantum yield, and photostability of fluorescent SLB-AuNCs. The obtained SLB-AuNCs possessed good monodispersity with an average diameter of 2.9 ± 0.8 nm and exhibited highly stable fluorescence with maximum emission at 480 nm under physiological conditions. A ratiometric fluorescent probe for hROS was developed through an oxidization-regulated Förster-resonance-energy-transfer process between SLB-AuNCs and 2,3-diaminophenazine (the oxidative product of hROS and

Salvia miltiorrhiza (Danshen), as an important traditional Chinese medicinal plant, has been used in China for the treatment of cardiovascular diseases for hundreds of years. Salvianolic acids (salvianolic acid A and salvianolic acid B) as the most abundant water-soluble component extracted from Salvia miltiorrhiza have attracted more and more attention from cardiovascular scientists due to its comprehensive cardiovascular actions. In vivo and in vitro studies have rendered salvianolic acid an excellent drug candidate for the treatment and prevention of cardiovascular diseases. In this review, we surveyed the protective effects of salvianolic acid A and salvianolic acid B against cardiovascular diseases and the pharmacological basis, providing a strong scientific rationale for elucidating the important role of Salvia miltiorrhiza in cardiovascular therapy. More importantly, we also hope to provide new inspiration and perspectives on the development and innovation of small-molecule cardiovascular drugs based on salvianolic acid.

Background Salt stress is a serious abiotic stress that caused crop growth inhibition and yield decline. Previous studies have reported on the the synthesis of gamma-aminobutyric acid (GABA) and its relationship with plant resistance under various abiotic stress. However, the relationship between exogenous GABA alleviating plant salt stress damage and ion flux, amino acid synthesis, and key enzyme expression remains largely unclear. We investigated plant growth, Na+ transportation and accumulation, reactive oxygen species (ROS) metabolism and evaluated the effect of GABA on amino acids, especially SlGADs gene expression and the endogenous GABA content of tomato (Solanum lycopersicum L.) seedlings treated with or without 5 mmol·L− 1 GABA under 175 mmol·L− 1 NaCl stress. Results Exogenous application of GABA significantly reduced the salt damage index and increased plant height, chlorophyll content and the dry and fresh weights of tomato plants exposed to NaCl stress. GABA significantly reduced Na+ accumulation in leaves and roots by preventing Na+ influx in roots and transportation to leaves. The transcriptional expression of SlGAD1–3 genes were induced by NaCl stress especially with GABA application. Among them, SlGAD1 expression was the most sensitive and contributed the most to the increase in glutamate decarboxylase (GAD) activity induced by NaCl and GABA application; Exogenous GABA increased GAD activity and amino acid contents in tomato leaves compared with the levels under NaCl stress alone, especially the levels of endogenous GABA, proline, glutamate and eight other amino acids. These results indicated that SlGADs transcriptional expression played an important role in tomato plant resistance to NaCl stress with GABA application by enhancing GAD activity and amino acid contents. GABA significantly alleviated the active oxygen-related injury of leaves under NaCl stress by increasing the activities of antioxidant enzymes and decreasing the contents of active oxygen species and malondialdehyde. Conclusion Exogenous GABA had a positive effect on the resistance of tomato seedlings to salt stress, which was closely associated with reducing Na+ flux from root to leaves, increasing amino acid content and strengthening antioxidant metabolism. Endogenous GABA content was induced by salt and exogenous GABA at both the transcriptional and metabolic levels.

The discovery of X-rays in 1895 had a dramatic impact on many aspects of society. One was the hope that it would be possible to treat some of the numerous infections and inflammatory conditions for...

Two efficient photosensitizers (PSs) with aggregation-induced emission characteristics were designed and synthesized for specific lysosome-targeted photodynamic therapy (PDT). Both PSs efficiently discriminated Gram-positive bacteria from Gram-negative bacteria and killed Gram-positive bacteria through the PDT effect.