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Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The accumulation of reactive oxygen species (ROS) is a widespread defence mechanism in higher plants against pathogen attack and sometimes is the cause of cell death that facilitates attack by necrotrophic pathogens. Plant pathogens use superoxide dismutase (SOD) to scavenge ROS derived from their own metabolism or generated from host defence. The significance and roles of SODs in the vascular plant pathogen Verticillium dahliae are unclear. Our previous study showed a significant upregulation of Cu/Zn-SOD1 (VdSOD1) in cotton tissues following V. dahliae infection, suggesting that it may play a role in pathogen virulence. Here, we constructed VdSOD1 deletion mutants (ΔSOD1) and investigated its function in scavenging ROS and promoting pathogen virulence. ΔSOD1 had normal growth and conidiation but exhibited significantly higher sensitivity to the intracellular ROS generator menadione. Despite lacking a signal peptide, assays in vitro by western blot and in vivo by confocal microscopy revealed that secretion of VdSOD1 is dependent on the Golgi reassembly stacking protein (VdGRASP). Both menadione-treated ΔSOD1 and cotton roots infected with ΔSOD1 accumulated more O 2 - and less H 2 O 2 than with the wildtype strain. The absence of a functioning VdSOD1 significantly reduced symptom severity and pathogen colonization in both cotton and Nicotiana benthamiana. VdSOD1 is nonessential for growth or viability of V. dahliae, but is involved in the detoxification of both intracellular ROS and host-generated extracellular ROS, and contributes significantly to virulence in V. dahliae., (© 2021 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: The rhizome of Anemone raddeana Regel (A. raddeana) is a famous traditional Chinese medicine (TCM) recorded in Chinese Pharmacopoeia for the treatment of carbuncle and swelling. Carbuncle swollen is an explanation of tumor in the theory of TCM and softening and resolving hard mass effects are one of the important pharmacological activities of A. raddeana., Aim of the Study: We investigated the potential anti-breast cancer effect and toxicological properties of alkali-ethanol extract from A. raddeana, namely total secondary saponin (TSS)., Materials and Methods: Anti-proliferative effect of total saponin of A. raddeana (ATS) and TSS were tested using MTT assay. Hoechst staining, flow cytometry analysis, DCFH-DA fluorescence microscopy and western blot were carried out to evaluate the mechanisms of action of TSS. The potential anti-breast cancer activity and toxicological properties of TSS were tested in vivo., Results: ATS and TSS could inhibit the proliferation of A549, HepG2, MCF-7, MDA-MB-231 and SKBr-3 cells, especially for MCF-7 cells. Flow cytometry analysis revealed that TSS (10, 12 and 15 μg/ml) could induce cell cycle arrest on G0/G1 phase and promote apoptosis of MCF-7 cells. TSS could increase Bax/Bcl-2 ratio, elevate cytochrome c levels in cytosol and activate caspase-3/9. In addition, TSS also induced ROS generation and inactivated PI3K/AKT/mTOR pathway which may involved in the mitochondrial dysfunction of MCF-7 cells. TSS showed slight toxic at the dosage of 100 and 200 mg/kg by oral administration without any toxic potential for 28 days. TSS (50, 100 and 200 mg/kg) showed significant inhibitory effect on growth of transplanted tumor in mice. At last, twenty-three C-3 monosaccharide oleanane-type triterpene saponins were tentatively identified, which may contributed to the anti-cancer activity of TSS., Conclusion: This study demonstrated that TSS exhibited anti-proliferative and pro-apoptosis activities on MCF-7 cells via ROS-mediated activation of mitochondrial apoptosis pathway. TSS might be used as chemotherapeutic agent for the treatment of breast cancer with relatively low toxicity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Imbalanced T-helper (TH)1/Th2 response contributes significantly to asthma pathogenesis. Our study indicated that HMGB1 play an important role in the release of Th2-associated cytokines of asthma. However, the specific mechanism about HMGB1-induced imbalanced TH1/Th2 response is not known. In vivo, an OVA-induced asthma mouse model was set up and mice treated with anti-HMGB1 IgG. The mice treated with the anti-HMGB1 IgG ameliorated airway hyper-reactivity, disruption of Th1/Th2 balance and the upregulation of GRP75 induced by OVA. In vitro, the exposure of normal human bronchial epithelial cells to HMGB1 resulted in the upregulation of GRP75, proinflammatory cytokine production, enhanced ER-Mitochondrial Ca 2+ transfer, and enhancement of reactive oxygen species (ROS). While HMGB1-induced these changes were attenuated by GRP75 siRNA treatment. Sequentially, pretreatment with 2-APB, SKF960365 (SKF) and Ru360 which inhibit ER-Mitochondrial Ca 2+ transfer significantly lowered HMGB1-induced the generation of ROS and the release of Th2 cytokines in 16HBE cells. Meanwhile, N-acetylcysteine (NAC) significantly attenuated the HMGB1-mediated pro-inflammatory cytokines release. Therefore, these results indicate that GRP75-mediated ER-Mitochondrial Ca 2+ transfer may be an important contributor in imbalanced of Th1/Th2 balance of asthma. Moreover, HMGB1 specifically induces the release of Th2 cytokines through GRP75-mediated enhancement of ER-Mitochondrial Ca 2+ transfer and ROS increased., (© 2018 Wiley Periodicals, Inc.)

2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.

Axillary bud is an important aspect of plant morphology, contributing to the final tobacco yield. However, the mechanisms of axillary bud development in tobacco remain largely unknown. To investigate this aspect of tobacco biology, the metabolome and proteome of the axillary buds before and after topping were compared. A total of 569 metabolites were differentially abundant before and 1, 3, and 5 days after topping. KEGG analyses further revealed that the axillary bud was characterized by a striking enrichment of metabolites involved in flavonoid metabolism, suggesting a strong flavonoid biosynthesis activity in the tobacco axillary bud after topping. Additionally, 9035 differentially expressed proteins (DEPs) were identified before and 1, 3, and 5 days after topping. Subsequent GO and KEGG analyses revealed that the DEPs in the axillary bud were enriched in oxidative stress, hormone signal transduction, MAPK signaling pathway, and starch and sucrose metabolism. The integrated proteome and metabolome analysis revealed that the indole-3-acetic acid (IAA) alteration in buds control dormancy release and sustained growth of axillary bud by regulating proteins involved in carbohydrate metabolism, amino acid metabolism, and lipid metabolism. Notably, the proteins related to reactive oxygen species (ROS) scavenging and flavonoid biosynthesis were strongly negatively correlated with IAA content. These findings shed light on a critical role of IAA alteration in regulating axillary bud outgrowth, and implied a potential crosstalk among IAA alteration, ROS homeostasis, and flavonoid biosynthesis in tobacco axillary bud under topping stress, which could improve our understanding of the IAA alteration in axillary bud as an important regulator of axillary bud development. [ABSTRACT FROM AUTHOR]

Verticillium wilt caused by Verticillium dahliae is a notorious soil-borne fungal disease and seriously threatens the yield of economic crops worldwide. During host infection, V. dahliae secretes many effectors that manipulate host immunity, among which small cysteine-rich proteins (SCPs) play an important role. However, the exact roles of many SCPs from V. dahliae are unknown and varied. In this study, we show that the small cysteine-rich protein VdSCP23 inhibits cell necrosis in Nicotiana benthamiana leaves, as well as the reactive oxygen species (ROS) burst, electrolyte leakage and the expression of defense-related genes. VdSCP23 is mainly localized in the plant cell plasma membrane and nucleus, but its inhibition of immune responses was independent of its nuclear localization. Site-directed mutagenesis and peptide truncation showed that the inhibition function of VdSCP23 was independent of cysteine residues but was dependent on the N-glycosylation sites and the integrity of VdSCP23 protein structure. Deletion of VdSCP23 did not affect the growth and development of mycelia or conidial production in V. dahliae. Unexpectedly, VdSCP23 deletion strains still maintained their virulence for N. benthamiana, Gossypium hirsutum and Arabidopsis thaliana seedlings. This study demonstrates an important role for VdSCP23 in the inhibition of plant immune responses; however, it is not required for normal growth or virulence in V. dahliae. [ABSTRACT FROM AUTHOR]

Antibiotic pollution has been a serious global public health concern in recent years, photodynamic inactivation is one of the most promising and innovative methods for antibacterial applications that avoids antibiotic abuse and minimizes risks of antibiotic resistance. However, limited by the weak interaction between the photosensitizers and Gram-negative bacteria, the effect of photodynamic inactivation cannot be fully exerted. Herein, photosensitizer chlorin e6-loaded polyethyleneimine-based micelle was constructed. The synergy of electrostatic and hydrophobic interactions between the nanoparticles and the bacterial surface promoted the anchoring of nanoparticles onto the bacteria, resulting in enhanced photoinactivation activities on Gram-negative bacteria. As expected, an eminent antibacterial effect was also observed on the Gram-positive bacteria Staphylococcus aureus. The cellular uptake results showed that photosensitizer was firmly anchored to the bacterial cell surface of Escherichia coli or Staphylococcus aureus by the introduction of branched polyethylenimine-containing nanoparticles. The light-triggered generation of reactive oxygen species, mainly singlet oxygen, from the membrane-bound nanoparticles caused irreversible damage to the bacterial outer membrane, achieving enhanced bactericidal efficiency than free photosensitizer. The study would provide an efficient and promising antimicrobial alternative to prevent overuse of antibiotics and have enormous potential for human healthcare and the environment remediation. [ABSTRACT FROM AUTHOR]

6-Benzylaminopurine (BAP), a synthetic cytokinin, can elicit plant growth and development by stimulating cell division. In this study, the effects of BAP on decay and pericarp browning of harvested litchi fruit in relation to phenolics and ROS metabolism were investigated. Application of BAP significantly inhibited decay incidence of harvested litchi, associated with a direct inhibition on Peronophythora litchii, the major pathogenic fungi. In addition, BAP-treated fruit showed significantly lower pericarp browning, accompanied by reduced PPO activity, increased PAL activity and higher contents of anthocyanin and total phenolic compounds. Moreover, BAP reduced H 2 O 2 accumulation and lipid peroxidation, which may account for browning inhibition to an extent. Furthermore, higher activities of SOD, CAT and APX and DPPH radical scavenging capacity in BAP-treated fruit possibly benefited reducing ROS accumulation and lipid peroxidation. Overall, application of BAP showed great potential to control decay and browning and extend shelf life of harvested litchi. [ABSTRACT FROM AUTHOR]

Abstract: Structural dissimilarities of hexabromocyclododecane diastereoisomers could raise substantial differences in physicochemical, biological and toxicological properties. In order to fully assess the environmental safety and health risk of hexabromocyclododecanes (HBCDs), zebrafish embryos were used to evaluate the developmental toxicity of individual HBCD diastereoisomers (α-HBCD, β-HBCD and γ-HBCD). Four-hour post-fertilization (hpf) zebrafish embryos were exposed to different concentrations of HBCD diastereoisomers (0, 0.01, 0.1 and 1.0mg/l) until 120hpf. The results showed that exposure to HBCDs can affect the development of zebrafish embryos/larvae in a dose-dependent and diastereoselective manner. The diastereoisomers α-, β- and γ-HBCD at 0.01mg/l had little effect on the development of zebrafish embryos except that exposure to 0.01mg/l γ-HBCD significantly delayed hatching (P <0.05). At 0.1mg/l, α-HBCD resulted in depressed heart rate of larvae (96hpf) and delayed hatching, whereas β- and γ-HBCD both caused significant hatching delay and growth inhibition (P <0.05). In addition, a remarkable and significant increase in mortality and malformation rate was noted at 0.1mg/l γ-HBCD exposure groups (P <0.05). At 1.0mg/l, α-, β- and γ-HBCD significantly affected all of the endpoints monitored (P <0.05). Additionally, HBCD diastereoisomers could induce the generation of reactive oxygen species (ROS) and the activities of caspase-3 and caspase-9 in a dose-dependent manner. The results indicated that HBCD diastereoisomers could cause developmental toxicity to zebrafish embryos through inducing apoptosis by ROS formation. The overall results showed a good agreement confirming that the order of developmental toxicity of HBCD diastereoisomers in zebrafish is γ-HBCD>β-HBCD>α-HBCD. [Copyright &y& Elsevier]

Plant pathogens generally employ superoxide dismutase (SOD) to detoxify host defense reactive oxygen species (ROS), and to scavenge ROS derived from their own metabolism. However, the roles of SODs in an important vascular pathogen, Verticillium dahliae, are unclear. Our previous study has shown that a putative signal-peptide-lacking manganese superoxide dismutase (VdSOD3) is present in the exoproteome of V. dahliae cultured in tissues of host cotton, suggesting that VdSOD3 may be exported out of the fungal cells and contribute to the SOD activity extracellularly. Here, we confirm that the N-terminal of VdSOD3 is not a functional signal peptide by yeast signal trap assay. Despite lacking the signal peptide, the extracellular distribution of VdSOD3 was observed in planta by confocal microscopy during infection. Loss-of-function of VdSOD3 decreased extracellular and intracellular SOD activities of V. dahliae by 58.2% and 17.4%, respectively. Deletion mutant of VdSOD3 had normal growth and conidiation but showed significantly reduced virulence to susceptible hosts of cotton and Nicotiana benthamiana. Our data show that signal-peptide-lacking VdSOD3 is a dual function superoxide dismutase, localizing and functioning intracellularly and extracellularly. Whereas nonessential for viability, VdSOD3 plays a vital role in the virulence of V. dahliae. [ABSTRACT FROM AUTHOR]

• Novel nanocopper-loaded black phosphorus (BP/Cu) nanocomposites were synthesized. • The antibacterial effect is amplified after doped black phosphorus with nanocopper. • ROS burst was detected and the responsible ROS species were determined. Novel nanocopper-loaded black phosphorus (BP/Cu) nanocomposites were synthesized to synergistically exert enhanced antibacterial activities aimed at reducing antibiotics abuse. First, both BP and Cu display low biotoxicity, broadening their application in the microbiological field. Second, the unique electronic properties of BP enable BP/Cu nanocomposites to amplify antibacterial effects via interfacial charge transfer, resulting in a surge of reactive oxygen species (ROS). Third, BP/Cu nanocomposites are relatively stable, which helps to avoid the problem that nanocopper alone is highly oxidized. Finally, BP/Cu was synthesized in an environmentally-friendly manner by a one-step reduction method. The BP/Cu nanocomposites were characterized by transmission electron microscopy and atomic force microscopy. Their antibacterial properties were investigated comprehensively and discussed in detail by inhibition zone assays, dynamic growth curves, membrane potential assays, and live/dead baclight bacterial viability assays, all of which revealed the antimicrobial activities of BP/Cu nanocomposites. Absorption spectra were measured to determine which ROS species were responsible for the bactericidal mechanisms. In summary, our results demonstrated the potential of nanocomposites based on BP in antibacterial therapy due to its excellent electronic properties and outstanding biological performance. This will pave the way for avoiding antibiotic overuse and for providing security to humans and the environment. [ABSTRACT FROM AUTHOR]

Achyranthes plays the role of dredging the meridians and clearing the joints with a certain anti-inflammatory effect, peripheral analgesic activity and central analgesic activity. A novel self-assembled nanoparticles containing Celastrol (Cel) with matrix metalloproteinase (MMP)-sensitive chemotherapy-sonodynamic therapy was fabricated targeting macrophages at the inflammatory site of rheumatoid arthritis. Dextran sulfate (DS) with highly expressed SR-A receptor on the surface of macrophages is used to specifically target the site of inflammation; by introducing PVGLIG enzyme-sensitive polypeptides and ROS-responsive bonds, it can achieve the desired effect on MMP-2/9 and reactive oxygen species at the joint site. The preparation forms DS-PVGLIG-Cel&Abps-thioketal-Cur@Cel nanomicelles, referred to as D&A@Cel. The resulting micelles had an average size of 204.8 nm and the zeta potential −16.46 mV. The results show that activated macrophages can effectively capture Cel in in vivo experiments, indicating that Cel delivered by nanoparticles can significantly improve bioavailability. Fig. 1 Design and schematic illustration of Achyranthes polysaccharide based dual-responsive nano-delivery system. In the ancient classic prescription "Shentong Zhuyu Decoction", Achyranthes plays the role of dredging the meridians and clearing the joints. It can be used as a medicinal guide, guiding its medicinal power to descend to the lower part of the body to treat the "disease in the lower part". In addition, Achyranthes has a certain anti-inflammatory effect, peripheral analgesic activity and central analgesic activity. Construction of cross-linked self-assembled nanoparticles with matrix metalloproteinase (MMP)-sensitive chemotherapy-sonodynamic combination therapy targeting macrophages at the inflammatory site of rheumatoid arthritis, overcoming the low water solubility of triptolide and targeting unspecific question. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The effects of reactive oxygen species (ROS), especially hydroxyl radical ( OH), on cellular wall disassembly in vitro and in vivo, and aril breakdown in longan fruit, were investigated. OH caused the disassembly of cell wall material (CWM) in vitro, demonstrated by the increases of total sugars and uronic acid released, and the downshift in molecular mass of CDTA soluble pectin (CSP) and Na2CO3 soluble pectin (CO3-SP). In addition, OH resulted in decreased CO3-SP content and increased CSP content in CWM suspension, suggesting the conversion of CO3-SP to CSP. Application of exogenous OH accelerated aril breakdown in longan fruit while the process was delayed by l-cysteine·HCl, a ROS scavenger. Furthermore, lower CWM content and decreased molecular mass of pectins were observed in OH-treated fruit. These results indicated that OH contributed to the degradation of cell wall polysaccharides, resulting in aril breakdown in longan fruit. [Copyright &y& Elsevier]

Abstract: The effects of pure oxygen on pericarp browning, reactive oxygen species (ROS) metabolism, antioxidant enzyme and antioxidant activity of harvested litchi fruit were investigated. Application of pure oxygen significantly prevented pericarp browning and delayed the increase in membrane permeability of litchi fruit during storage. Litchi fruit exposed to pure oxygen showed a lower level of lipid peroxides, compared to control fruit, with the delay in the increases of both H2O2 content and superoxide production rate. Furthermore, it was found that the treatment with pure oxygen induced the activities of superoxide dismutase (SOD), ascorbated peroxidase (APX) and catalase (CAT), which could be beneficial in scavenging of H2O2 and superoxide and alleviating lipid peroxidation. In addition, antioxidant ability (reducing power and free-radical scavenging activity against DPPH radical, superoxide anions and hydroxyl radical) of methanol extracts from litchi fruit pericarp declined gradually, with decreasing contents of anthocyanins and phenolic compounds, as storage time of the fruit progressed. There was a linear relationship between the contents of either anthocyanins or phenolic compounds and antioxidant ability or free radical scavenging activity. Treatment with pure oxygen markedly increased antioxidant ability, which was related to higher levels of anthocyanins and phenolic compounds, compared with those of control fruit. It is suggested that enhanced antioxidant activity and antioxidant enzyme induced by pure oxygen may contribute to alleviating lipid peroxidation and maintenance of membrane integrity, which reduced decompartmentation of enzymes and substrates, resulting in enzymatic browning. [Copyright &y& Elsevier]

Reactive oxygen species (ROS) play a role in aging and senescence in organisms. The oxidation of methionine (Met) residues in proteins to Met sulfoxide by ROS can cause conformational alteration and functional impairments. Met oxidation is reversed by Met sulfoxide reductase (Msr) A and B. Currently, the repair of oxidized proteins by Msr and Msr-mediated physiological functions are not well understood, especially in higher plants. The down-regulated expression of LcMsrA1/B1 may be involved in the senescence of litchi ( Litchi chinensis ) fruit. We verified that LcCaM1 is a substrate of LcMsrA1 and LcMsrB1 in vitro and in vivo , and oxidized LcCaM1 could be repaired by LcMsrA1 in combination with LcMsrB1. Moreover, LcMsrA1 and LcMsrB1 play important roles in repairing oxidized Met110 and Met125 residues, respectively, in LcCaM1. Furthermore, the Met oxidation in LcCaM1 did not affect its physical interactions with two LcCaM1-binding senescence-related transcription factors LcNAC13 and LcWRKY1, but enhanced their DNA-binding activities. Therefore, we hypothesized that the down-regulated expression of LcMsrA1/B1 results in the accelerated oxidation of LcCaM1, which enhanced the DNA-binding activities of LcNAC13 and LcWRKY1, thereby activating or repressing the expression of senescence-related genes. [ABSTRACT FROM AUTHOR]

• Expression of DlTrx1 and DlNRT1 were upregulated with fruit quality deterioration. • Thirty-three potential Trx target proteins in longan were identified. • Gpx was one target protein of Trx in longan fruit. • DlTrx regulated redox state and activity of DlGpx. • Redox state of DlGpx is related to fruit senescence or quality deterioration. Thioredoxins (Trxs) are important redox regulators in organisms. However, their involvement in fruit senescence and quality deterioration remains unclear. In this study, one Trx (DlTrx1) and one NADPH-dependent Trx reductase (DlNRT1) cDNAs, were cloned from longan fruit. The DlTrx1 could be effectively reduced by the DlNTR1. Expression of DlTrx1 and DlNTR1 were up-regulated during fruit senescence and quality deterioration. We further identified 33 potential Trx target proteins in longan, including one glutathione peroxidase (DlGpx). DlTrx1 could physically interact with DlGpx. DlTrx1 in combination with DlNTR1 effectively activated DlGpx activity by regulating its redox state. Cys90 in DlGPx could form a disulfide bond with either Cys42 or Cys71, which were the sites of redox modulation. Furthermore, DlGpx exhibited a higher ratio of disulfide bonds to sulfhydryl groups in senescent or deteriorative fruit. We propose that Trx-mediated redox regulation of DlGpx is involved in senescence or quality deterioration of harvested longan fruit. [ABSTRACT FROM AUTHOR]