Release Of Reactive Oxygen Species Research Articles

Combined treatment using novel multifunctional MAu-GelMA hydrogel loaded with neural stem cells and electrical stimulation promotes functional recovery from spinal cord injury

The massive death of nerve cells and the inflammatory microenvironment resulting from the release of reactive oxygen species after spinal cord injury (SCI) hinders the subsequent reconstruction of motor function. Owing to complex pathological changes, combination therapy is a potential new way to treat SCI. In this study, a novel multifunctional hydrogel containing an MXene-Au complex was constructed, and neural stem cells (NSCs) loaded in the hydrogel were combined with electrical stimulation to promote the recovery of motor function after SCI in rats. The constructed MAu-GelMA hydrogel had good reactive oxygen species-scavenging ability, electrical conductivity, and antibacterial ability. Simultaneously, electrical stimulation promoted the proliferation and differentiation of NSCs into nerve cells and promoted the establishment of synaptic connections between neurons. In the rat SCI model, combined treatment using MAu-GelMA hydrogel carrying NSCs and electrical stimulation reduced the formation of cavities and glial scars, enhanced neuronal differentiation and myelin regeneration of NSCs in the injured area, and promoted the recovery of motor function after SCI. In conclusion, in this study, we constructed a novel multifunctional hydrogel capable of carrying NSCs, which upon combining with electrical stimulation during treatment, effectively promoted the recovery of motor function in rats with SCI, thereby providing a new combination therapy strategy for SCI.

Anti-inflammatory Activity of Tanshinone-Related Diterpenes from Perovskia artemisioides Roots.

Perovskia artemisioides is a perennial and aromatic plant widely distributed in the Baluchestan region of Iran. Phytochemical analysis of a n-hexane extract of P.artemisioides roots, guided by an analytical approach based on LC-ESI/LTQOrbitrap/MS/MS, yielded six previously undescribed diterpenoid compounds (2, 9-11, 16, and 20), and 19 known diterpenoids, for which the structures were elucidated by 1D and 2D NMR experiments. Some of the isolated compounds showed significant anti-inflammatory activity using J774A.1 macrophage cells stimulated with Escherichia coli lipopolysaccharide. In particular, compounds 6, 8, 17, 18, 20, and 22 significantly inhibited the release of nitric oxide and the expression of related pro-inflammatory enzymes, such as inducible nitric oxide synthase and cycloxygenase-2. Moreover, two compounds that showed the highest activity in reducing nitric oxide release (6 and 18) were tested to evaluate their effects on nitrotyrosine formation and reactive oxygen species release. Both compounds inhibited ROS release and, in particular, compound 6 also inhibited nitrotyrosine formation at all tested concentrations, thus indicating a significant antioxidant potential.

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis.

The imbalance between osteogenesis and osteoclastogenesis is a feature of bone metabolic disease. Cadmium (Cd) exposure causes human bone loss and osteoporosis (OP) through bioaccumulation of the food chain. However, the impact of Cd on bone tissues and the underlying molecular mechanisms are not well-characterized. In the current study, we found that the Cd concentration in bone tissues of OP patients was higher than normal subjects; meanwhile, the nuclear silent information regulator of transcription 1 (SIRT1) protein expression level was significantly decreased, which is a new star molecule to treat OP. It is further revealed that SIRT1 activation markedly reprograms bone metabolic and stress-response pathways that incline with osteoblast (OB) apoptosis. Suppressing reactive oxygen species (ROS) release with N-acetyl-l-cysteine (NAC) abolished Cd-induced reduction of SIRT1 protein, deacetylation of P53, OB apoptosis, and attenuated OP. Conversely, overexpression of SIRT1 suppressed Cd-induced ROS release. SIRT1 overexpression in vivo and in vitro dampened PGC-1α protein, acetylation of P53 at lysine 382, and caspase-dependent apoptosis. These results reveal that ROS/SIRT1 controls P53 acetylation and coordinates OB apoptosis involved in the onset of OP.

Abstract 5146: In vitro neutrophil assays to support immuno-oncology drug development

Abstract Neutrophils have shown a lot of plasticity with important consequences on cancer disease progression and have been associated with multiple functions such as killing antibody-opsonized cancer cells, directly kill tumor cells through the release of reactive oxygen and nitrogen species and a controversial role in the tumor micro-environment with both pro- and anti-tumor roles. Studying neutrophil function in vitro can be done using the Incucyte® live imaging system to monitor antibody-dependent cell-mediated cytotoxicity (ADCC). Optimised in vitro assays using fresh human neutrophils and fluorescent-labeled tumor cells can be used to screen the potency of candidate therapeutics. Additionally, neutrophil chemotaxis can be monitored using transwell plates and live imaging via Incucyte®. Finally, multiplex cytokine and chemokine analysis after activation and stimulation of neutrophils can be evaluated using Luminex technology. When studying neutrophil activity in vitro, important factors such as access to fresh blood and optimized protocols for purifying untouched neutrophils are key for reproducible and reliable results. Citation Format: Alanah Pieters, Martijn Vlaming, Jezabel Lefevere, Sofie Pattyn. In vitro neutrophil assays to support immuno-oncology drug development. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5146.

Degradation mechanisms of 2-chlorophenol by Acinetobacter sp.: Exploring cellular membrane structure, intra- and extracellular components, and transcriptomic analysis

Chlorophenols (CPs) are widespread environmental contaminants with mutagenic, carcinogenic, and teratogenic properties. Their biodegradability is limited by the presence of strongly electronegative chloride ions, prompting the use of biostimulation strategies to enhance degradation. However, there is still a gap in the investigation of the mechanisms of the effect of different biostimulants. The current study investigates the effects of polymerized ferric sulfate (PFS), fulvic acid (FA), and extracellular microalgal metabolites (EMA) on stimulating 2-chlorophenol (2-CP) degradation by Acinetobacter sp. strain ZY1 and elucidates the underlying mechanisms. Results indicate that the addition of these biostimulants increased 2-CP degradation efficiency by 21.5–46.7 %. Physiological analysis revealed that biostimulants restored ZY1 morphology under 2-CP stress, reduced reactive oxygen species (ROS) release, and mitigated membrane damage. PFS addition led to a 2.1-fold increase in EPS-PN secretion. Transcriptomic analysis showed upregulation of genes related to membrane composition, transmembrane transport, metabolism, and cell proliferation. Enhanced 2-CP degradation resulted from accelerated bacterial metabolism and proliferation, resistance to 2-CP stress, and increased activity of degrading enzymes like oxygenase and hydrolase. These findings provide a theoretical basis for chlorophenol removal via biostimulation at physiological and molecular levels.

Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

LOSS OF EPITHELIAL DUOX2 SIGNALING IS ACCOMPANIED BY A REDUCTION IN AKKERMANSIACEAE AND PROMOTES THE DEVELOPMENT OF METABOLIC SYNDROME IN A MICROBIOME-DEPENDENT MANNER

Dysbiosis, an imbalance in microbial composition or function, is a key player in the development of conditions associated with chronic inflammation. The gut epithelium regulates host-microbiome dynamics through a variety of mechanisms, including the release of reactive oxygen species by NADPH oxidases. Dual oxidase 2 (DUOX2) is an antimicrobial NADPH oxidase expressed in the thyroid gland and gut epithelium and its activity is associated with dysbiosis. Loss of function mutations in DUOX2 are linked to the development of metabolic and inflammatory conditions such as congenital hypothyroidism and inflammatory bowel disease. Metabolic syndrome (MetS) is a cluster of conditions characterized by dysbiosis, inflammation, obesity, glucose intolerance, and hepatic steatosis. Dysbiosis in MetS is associated with a reduction in Bacteroidaceae and Akkermansiaceae. Despite this association, the mechanism by which dysbiosis leads to chronic inflammation and MetS is poorly defined. Here, we investigate the relationship between impaired epithelial barrier function and the development of MetS by focusing for the first time on intestinal specific DUOX2 deficiency as a mechanistic link.

Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis.

Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants.

Death of tonsillar B cells by NETosis

Regulating B cell death is essential for generating antibodies and maintaining immune tolerance. B cells can die by apoptosis, and we report that human tonsil B cells, but not peripheral blood B cells also die by NETosis. This cell death is density-dependent, characterized by the loss of cell and nuclear membrane integrity, release of reactive oxygen species, and chromatin decondensation. Tonsil B cells secrete high levels of TNF, and inhibiting TNF prevented chromatin decondensation. By in situ fluorescence microscopy, B cell NETosis, as identified by the hyper citrullination of Histone-3, was localized to the light zone (LZ) of germinal centers in normal tonsil and overlapped with the B cell marker CD19/IgM. We propose a model in which stimulation of B cells in the LZ induces NETosis, driven in part by TNF. We also provide evidence that NETosis of tonsil B cells may be inhibited by an unidentified factor in tonsil. The results describe a previously unidentified form of B cell death and suggest a new mechanism to maintain B cell homeostasis during immune responses.

A PI3K-calcium-Nox axis primes leukocyte Nrf2 to boost immune resilience and limit collateral damage.

Phagosomal reactive oxygen species (ROS) are strategically employed by leukocytes to kill internalized pathogens and degrade cellular debris. Nevertheless, uncontrolled oxidant bursts could cause serious collateral damage to phagocytes or other host tissues, potentially accelerating aging and compromising host viability. Immune cells must, therefore, activate robust self-protective programs to mitigate these undesired effects, and yet allow crucial cellular redox signaling. Here, we dissect in vivo the molecular nature of these self-protective pathways, their precise mode of activation, and physiological effects. We reveal Drosophila embryonic macrophages activate the redox-sensitive transcription factor Nrf2 upon corpse engulfment during immune surveillance, downstream of calcium- and PI3K-dependent ROS release by phagosomal Nox. By transcriptionally activating the antioxidant response, Nrf2 not only curbs oxidative damage but preserves vital immune functions (including inflammatory migration) and delays the acquisition of senescence-like features. Strikingly, macrophage Nrf2 also acts non-autonomously to limit ROS-induced collateral damage to surrounding tissues. Cytoprotective strategies may thus offer powerful therapeutic opportunities for alleviating inflammatory or age-related diseases.

IFN-γ Facilitates Corneal Epithelial Cell Pyroptosis Through the JAK2/STAT1 Pathway in Dry Eye.

To investigate the effect of gamma interferon (IFN-γ) on corneal epithelial pyroptosis in an experimental dry eye (DE) model and explore the underlying molecular mechanisms. Experimental DE was established in adult wild-type (WT) C57BL/6 mice and Ifng-knockout mice on a C57BL/6 background by subcutaneous injection of scopolamine (1.5 mg/0.3 mL, three times per day) and exposure to desiccating stress. An immortalized human corneal epithelial cell line (HCE-T) was treated with IFN-γ under hyperosmolar conditions. Corneal epithelial defects, tear production, and conjunctival goblet cells were detected by fluorescein sodium staining, the phenol red cotton test, and periodic acid-Schiff staining. The mRNA expression was measured by quantitative real-time PCR. Changes in protein expression were analyzed by Western blotting and immunofluorescence staining. Cell Counting Kit-8 and lactate dehydrogenase assays and in situ TUNEL staining were used to assess cell death. The expression of IFNG and its related genes was increased in the corneas of DE mice, whereas genetic deletion of Ifng ameliorated desiccating stress-induced dry eye symptoms. We further found that IFN-γ activated the JAK2/STAT1 signaling pathway inducing corneal epithelial pyroptosis. Topical application of a STAT1 inhibitor in vivo or siRNA targeting STAT1 in vitro suppressed pyroptosis of corneal epithelial cells. In addition, the production of reactive oxygen species (ROS) was elevated in DE, and a reduction in excessive ROS release prevented pyroptosis. The increase in IFN-γ participates in the pathogenesis of dry eye and promotes corneal epithelial pyroptosis by activating the JAK2/STAT1 signaling pathway. Oxidative stress might be in downstream of JAK2/STAT1, thereby contributing to pyroptosis.

Oridonin inhibits Hela cell proliferation via downregulation of glutathione metabolism: a new insight from metabolomics.

This study aims to elucidate Oridonin' s inhibitory mechanism to cervical cancer using metabolomics methods and pharmacological assays. Network pharmacology and KEGG pathway analysis are used to identify overlapped targets and involved metabolic pathways. UPLC-MS/MS metabolomics analysis is used to determine altered metabolites after Oridonin treatment. Other bioassays are also employed to uncover the changes in critical molecules that are highly related to altered metabolites. Seventy-five overlapped targets are identified between Oridonin and cervical cancer. Twenty-one metabolites involved in tricarboxylic acid cycle glutathione metabolism, branched-chain amino acid metabolism and so on changes significantly after Oridonin treatment. Oridonin treatment significantly reduces the content of cysteine and inhibit the catalytic activity of glutamine-cysteine ligase subunit, a rate-limiting enzyme for the synthesis of glutathione. As a result, the content of glutathione is also reduced. The antioxidant enzyme glutathione peroxidase 4 which uses glutathione as a cofactor, is inactivated, resulting in a burst release of reactive oxygen species. The ATP content is also significantly reduced in Hela cells after Oridonin treatment. This study finds that Oridonin treatment induces Hela cell apoptosis possibly via inhibition of the glutathione metabolism.

The Combined Treatment of Glutathione Sodium Salt and Ascorbic Acid for Preventing Contrast-Associated Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Hypothesis to Be Validated.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses.

Neurochemical effects of sepsis on the brain.

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.

Schwann cell insulin-like growth factor receptor type-1 mediates metastatic bone cancer pain in mice

Insulin growth factor-1 (IGF-1), an osteoclast-dependent osteolysis biomarker, contributes to metastatic bone cancer pain (MBCP), but the underlying mechanism is poorly understood. In mice, the femur metastasis caused by intramammary inoculation of breast cancer cells resulted in IGF-1 increase in femur and sciatic nerve, and IGF-1-dependent stimulus/non-stimulus-evoked pain-like behaviors. Adeno-associated virus-based shRNA selective silencing of IGF-1 receptor (IGF-1R) in Schwann cells, but not in dorsal root ganglion (DRG) neurons, attenuated pain-like behaviors. Intraplantar IGF-1 evoked acute nociception and mechanical/cold allodynia, which were reduced by selective IGF-1R silencing in DRG neurons and Schwann cells, respectively. Schwann cell IGF-1R signaling promoted an endothelial nitric oxide synthase-mediated transient receptor potential ankyrin 1 (TRPA1) activation and release of reactive oxygen species that, via macrophage-colony stimulating factor-dependent endoneurial macrophage expansion, sustained pain-like behaviors. Osteoclast derived IGF-1 initiates a Schwann cell-dependent neuroinflammatory response that sustains a proalgesic pathway that provides new options for MBCP treatment.

Targeting ER Stress with Saikosaponin A to Overcome Resistance under Radiation in Gastric Cancer Cells

Saikosaponin A is a triterpene saponin and a potentially bioactive compound derived from Bupleurum falcatum L. However, the molecular mechanisms and effects of saikosaponin A in gastric cancer remain unknown. In the present study, I evaluated the effects of saikosaponin A on cell death and endoplasmic reticulum stress via calcium and reactive oxygen species release. Targeting reactive oxygen species with diphenyleneiodonium and N-acetylcysteine inhibited cell death and protein kinase RNA-like ER kinase signaling pathway by down-regulating Nox4 and inducing glucose-regulated protein 78 exosomes. Furthermore, saikosaponin A caused a synergistic inhibitory effect of the epithelial mesenchymal transition phenomenon, indicating the reversible phenotype modulation by epithelial cells under radiation exposure in radiation-resistant gastric cancer cells. These results suggest that saikosaponin A-mediated calcium and reactive oxygen species-induced endoplasmic reticulum stress overcome radio-resistance and induce cell death under radiation in gastric cancer cells. Therefore, saikosaponin A in combination with radiation may be a potential strategy for gastric cancer therapy.

Targeted Magnetic Resonance Imaging/Near‐Infrared Dual‐Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

AbstractAccurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T1‐weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)‐loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid‐labile polymer mPEG (FeGdNP‐ICG/GOx‐RGD2‐mPEG). Compared with commercial Magnevist, the proposed FeGdNP‐ICG/GOx‐RGD2‐mPEG shows a two to three‐fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP‐ICG/GOx‐RGD2‐mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H2O2 are generated during the GOx‐mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence‐guided navigation, and ferroptosis tumor therapy.

Tumor microenvironment-responsive nanosystem achieves reactive oxygen species self-cycling after photothermal induction to enhance efficacy of antitumor therapy

Tumor microenvironment response and spatio-temporal targeting are promising strategies to combination therapy. By regulating the tumor microenvironment and realizing the precise targeted therapy, the antitumor efficacy can be significantly improved while maintaining low side effects. Therefore, in this study, a reactive oxygen species (ROS)-responsive nanosystem (MND-IR@RESV) was constructed. The MND-IR@RESV nanosystem could be accurately tracked and located due to its own fluorescence. Mitochondria-targeted nanosystem promoted the release of ROS and contributed to the apoptosis of cancer cells. The MND-IR@RESV responded significantly to ROS, which promoted the deep release of drugs. Furthermore, the system also possessed high photothermal conversion efficiency and photothermal stability, which could achieve spatio-temporal targeting of drugs and ensure the efficient tumor eradication ability of Chemo/Photothermal/Photodynamic (CT-PTT-PDT) combination therapy. Both in vitro and in vivo tests demonstrated the significant antitumor effect of the MND-IR@RESV. Importantly, the nanosystem had the advantages of low toxicity and few side effects that conventional CT lacks, indicating that the MND-IR@RESV holds great promise in future cancer treatment.

Stretchable Oxygen-Tolerant Sensor Based on a Single-Atom Fe-N4 Electrocatalyst for Observing the Role of Oxidative Stress in Hypertension.

Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.

The protective effect of Allium chinense on anti-cerebral anoxia through regulating NLRP3/NF-κB

Allium chinense G. Don is a popular medicinal and aromatic plant, known as “Ganoderma of vegetables” in history for treating blood stasis syndrome that reduces red blood cell oxygen-carrying capacity and often causes severe brain damage. However, the effect of A. chinense on cerebral anoxia remains obscure. Here, the anti-hypoxic effect of A. chinense was investigated for the first time through the cerebral anoxia model of mice. Subsequent a bio-guided investigation brought about the isolation of 16 compounds, including 9 phenolic derivatives (2 new compounds (compound 1, 8) and one new natural product (compound 2), 4 steroidal saponins and 3 fatty acid monoglycerides, among which, 6 compounds (1–4, 7, 16) exhibited significant anoxia-tolerant activity in vitro. Moreover, the release of reactive oxygen species (ROS) was decreased significantly, and glutathione (GSH) and lactate dehydrogenase (LDH) were regulated by the 6 bioactive compounds in oxygen‑glucose deprivation/ reoxygenation (OGD/R)-induced BV-2 cells damage. Besides that, protein expressions of HIF-1α, NLRP3, COX-2, NF-κB p65 and IL-18 were suppressed effectively. The investigation provided a new nutritional strategy for A. chinense against cerebral anoxia and altitude illness, which might be partially mediated by downregulating NLRP3/NF-κB.