High altitude hypoxia and oxidative stress: The new hope brought by free radical scavengers.

Various strategies can be employed to prevent and manage altitude illnesses, including habituation, oxygenation, nutritional support, and medication. Nevertheless, the utilization of drugs for the prevention and treatment of hypoxia is accompanied by certain adverse effects. Consequently, the quest for medications that exhibit minimal side effects while demonstrating high efficacy remains a prominent area of research. In this context, it is noteworthy that free radical scavengers exhibit remarkable anti-hypoxia activity. These scavengers effectively eliminate excessive free radicals and mitigate the production of reactive oxygen species (ROS), thereby safeguarding the body against oxidative damage induced by plateau hypoxia. In this review, we aim to elucidate the pathogenesis of plateau diseases that are triggered by hypoxia-induced oxidative stress at high altitudes. Additionally, we present a range of free radical scavengers as potential therapeutic and preventive approaches to mitigate the occurrence of common diseases associated with hypoxia at high altitudes.

The potential value of Notch1 and DLL1 in the diagnosis and prognosis of patients with active TB.

Objectives: The Notch signaling pathway has been implicated in the pathogenesis of active tuberculosis (TB), and Th1-type cell-mediated immunity is essential for effective control of mycobacterial infection. However, it remains unclear whether Notch signaling molecules (Notch1, DLL1, and Hes1) and Th1-type factors (T-bet and IFN-γ) can serve as biomarkers for tracking the progression of active TB at different stages along with peripheral blood white blood cell (WBC) parameters. Methods: A total of 60 participants were enrolled in the study, including 37 confirmed TB patients (mild (n=17), moderate/severe (n=20)) and 23 healthy controls. The mRNA expression of Notch1, DLL1, Hes1, T-bet and IFN-γ in the peripheral blood mononuclear cells (PBMCs) of the subjects was measured by RT-qPCR, then analyzed for differences. Receiver Operating Characteristic curve (ROC) was used to assess the effectiveness of each factor as a biomarker in identifying lung injury. Results: We found that mRNA expression levels of Notch1, DLL1, and Hes1 were upregulated in active TB patients, with higher levels observed in those with moderate/severe TB than those with mild TB or without TB. In contrast, mRNA levels of T-bet and IFN-γ were downregulated and significantly lower in mild and moderate/severe cases. Furthermore, the combiROC analysis of IFN-γ and the percentage of lymphocytes (L%) among WBC parameters showed superior discriminatory ability compared to other factors for identifying individuals with active TB versus healthy individuals. Notably, Notch pathway molecules were more effective than Th1-type factors and WBC parameters in differentiating mild and moderate/severe cases of active TB, particularly in the combiROC model that included Notch1 and Hes1. Conclusions: Our study demonstrated that Notch1, Hes1, IFN-γ, and L% can be used as biomarkers to identify different stages of active TB patients and to monitor the effectiveness of treatment.

Hierarchical Ni-Mo-P nanoarrays toward efficient urea oxidation reaction.

The urea oxidation reaction (UOR), which possesses a low theoretical potential and superior kinetics, is an attractive substitute for the anodic oxygen evolution reaction (OER) in overall water splitting; however, the implementation of hydrogen production in overall urea splitting is impeded by the deficiency of highly efficient, durable and cost-effective catalysts. Herein, we fabricated an Ni2P-MoP2 heterostructure with a hierarchical structure grown on carbon paper (Ni-Mo-P/CP), which exhibited robust activity and outstanding durability for the electrocatalytic oxidation of urea. The Ni-Mo-P/CP catalyst possessed an ultralow potential of 1.39 V to obtain the current density of 100 mA cm-2, small Tafel slope (27 mV dec-1) and long-term durability with almost no decay within 15 h. The experimental characterization revealed that the optimized electronic structure and the synergistic effect of abundant exposed active sites in the Ni-Mo-P/CP catalyst contribute to the efficient UOR catalytic activity. This work enriches the candidate catalysts for the UOR and promotes the industrial development of hydrogen production.

Correction: A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants.

Correction for 'A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants' by Fuxin Liu et al., Analyst, 2019, 144, 6905-6913, https://doi.org/10.1039/C9AN01693G.

Long non-coding RNA RNF7 promotes the cardiac fibrosis in rat model via miR-543/THBS1 axis and TGFß1 activation.

Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor ß1 (TGFß1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of TGFß activation. Here, we performed microarray analyses on mRNAs and lncRNAs differentially-expressed in the CF and normal rat hearts. KEGG signaling annotation and GO enrichment analyses were performed to validate the roles of extracellular matrix (ECM) and TSP1-enhanced TGFß activation in CF. The co-expression network between differentially-expressed lncRNAs and ECM-related factors was constructed to identify candidate lncRNAs and miRNAs. We found that lncRNA Homo sapiens ring finger protein 7 (lnc RNF7) was significantly correlated with TSP1 and ECM. Lnc RNF7 silence could attenuate isoproterenol (ISP)-induced CF in rat heart in vivo and in rat cardiac fibroblasts in vitro. Moreover, angiotensin II (Ang II) -induced CF in rat cardiac fibroblasts could also be attenuated by Lnc RNF7 silence. Furthermore, miR-543 could simultaneously target lnc RNF7 and 3' UTR of TSP1. Lnc RNF7 silence suppressed, while miR-543 inhibition promoted TSP1 protein and TGFß activation, as well as ECM markers expression. The effects of lnc RNF7 silence was significantly reversed by miR-543 inhibition. In conclusion, CF progression might be regulated by lnc RNF7/miR-543 axis via TSP1-mediated TGFß activation.

A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants.

Peroxynitrite anion (ONOO-) is a crucial reactive nitrogen species (RNS), which has aroused immense research interest in the biological and biomedical fields because aberrant expression levels of ONOO- are related to many diseases. In this work, a novel electrochemical sensor is described for the detection of peroxynitrite anion (ONOO-) released from living cells. It is constructed with a glassy carbon electrode (GCE) decorated with a nanocomposite (CTS-MPNS) synthesized from chitosan (CTS) functionalized microporous polymeric nanospheres (MPNS). The prepared CTS-MPNS/GCE sensor shows a supernormal manifestation in measuring ONOO- in a wide range of concentrations from 3.83 nM to 0.104 mM, and the detection limit is as low as 1.28 nM (S/N = 3), which makes it possible to detect trace amounts of ONOO- released from U87 cells. Significantly, the synergistic effect of different antioxidants on scavenging ONOO- in biological systems is further studied by an electrochemical method for the first time, which provides an efficient strategy for protecting cells against oxidative stress. The developed platform and the efficient strategy may pave the way for their future applications in the field of biomedicine and the treatment of cancer diseases.

A sensitively non-enzymatic amperometric sensor and its application in living cell superoxide anion radical detection.

Here, we report a nanocomposite composed of silver nanoparticles and multi-walled carbon nanotubes (AgNPs/MWNTs) utilized as an efficient electrode material for sensitive detection superoxide anion (O2•-). The procedure to synthesize AgNPs/MWNTs nanocomposites was green and facile. In the presence of functionalized multi-wall carbon nanotubes (MWNTs), silver nanoparticles (AgNPs) were in situ generated by chemical reduction of silver nitrate with glucose as a reducing and stabilizing agent to give the desired AgNPs/MWNTs nanocomposites. The nanocomposites can be easily used for the construction of an electrochemical sensor on glassy carbon electrode (GCE). The characterization of sensor and experimental parameters affecting its activity were investigated employing scanning electron microscopy (SEM), energy-dispersive X-ray spectrometer (EDS), X-ray diffraction (XRD), and cyclic voltammetry (CV). The resulted sensor exhibited favorable electrochemical performance for O2•- sensing with a low detection limit of 0.1192 nM and wide linear range of 6 orders of magnitude, which guarantees the capacity of sensitive and credible detection of O2•- released from living cells. Notably, a simulation experiment indicated the capacity to resist oxidative stress is limited in biological milieu. Thus this work has great potential for further applications in biological researches.

Construction of an ultrasensitive non-enzymatic sensor to investigate the dynamic process of superoxide anion release from living cells.

In this work, a novel non-enzymatic superoxide anion (O2•-) sensor was constructed based on Ag nanoparticles (NPs) / poly (amidoamine) (PAMAM) dendrimers and used to investigate the dynamic process of O2•- release from living cells. The AgNPs/PAMAM nanohybrids were characterized by transmission electron microscopy (TEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The fabricated electrode exhibited excellent catalytic activity toward the reaction of O2•- with a super low detection limit (LOD) of 2.530 × 10-13M (S/N = 3) and wide linear range of 8 orders of magnitude. It could fulfill the requirement of real-time measurement O2•- released from living cells. Furthermore, zymosan was chosen as the stimulant to induce O2•- generation from cancer cells (rat adrenal medulla pheochromocytoma cell (PC12)). The electrochemical experiment results indicated that the levels of intracellular O2•- depended on the amount of Zymosan. A large amount of O2•- generated in the living cells by added heavy stimulant could damage cells seriously. More importantly, a vitro simulation experiment confirmed the role of superoxide dismutase (SOD) for the first time because it could maintain the O2•- concentration at a normal physiological range. These findings are of great significance for evaluating the metabolic processes of O2•- in the biological system, and this work has the tremendous potential application in clinical diagnostics to assess oxidative stress.

Construction of a highly sensitive non-enzymatic sensor for superoxide anion radical detection from living cells.

A novel non-enzymatic superoxide anion (O2•-) sensor was fabricated based on Ag nanoparticles (NPs)/L-cysteine functioned carbon nanotubes (Cys-MWCNTs) nanocomposites and used to measure the release of O2•- from living cells. In this strategy, AgNPs could be uniformly electrodeposited on the MWCNTs surface with average diameter of about 20nm as exhibited by scanning electronmicroscopy (SEM). Electrochemical study demonstrated that the AgNPs/Cys-MWCNTs modified glassy carbon electrode exhibited excellent catalytic activity toward the reduction of O2•- with a super wide linear range from 7.00×10-11 to 7.41×10-5M and a low detection limit (LOD) of 2.33×10-11M (S/N=3). Meanwhile, the mechanism for O2•- reduction was also proposed for the first time. Importantly, this novel non-enzymatic O2•- sensor can detect O2•- release from cancer cells under both the external stimulation and the normal condition, which has the great potential application in clinical diagnostics to assess oxidative stress of living cells.

Apoptosis induced by weisiensin B isolated from Rabdosia weisiensis C.Y. Wu in K562.

The ent-kaurane diterpenoid weisinensis B shows significant cytotoxicity to human chronic myeloid leukemia K562 cells. It inhibits cell growth at low concentration and kills cells at high concentration. The compound induced cell apoptosis and necrosis mainly associated with G2/M phase cell cycle arrest and the ROS generation is the early event in weisiensin B induced cell apoptosis.

Comparison of visual function after multifocal and accommodative IOL implantation.

PURPOSE: To compare early visual function between patients undergoing phacoemulsification combined with multifocal and accommodative intraocular lens implantation. METHODS: A total of 112 patients with age-related cataract undergoing phacoemulsification in our hospital were recruited for this study and randomly assigned into multifocal (56 eyes; ZAM00 group) and accommodative (56 eyes; FLEX group) intraocular lens groups. Visual acuity and contrast sensitivity were statistically compared between the two groups. RESULTS: No significant difference was found in uncorrected distant visual acuity between the ZMA00 and FLEX groups at 1 week, or 1, 3, and 6 months after operation (all P > 0.05). At postoperative 6 months, no statistical significance was noted in distant and intermediate best-corrected visual acuity or in contrast sensitivity between the two groups (all P > 0.05). Patients in the ZMA00 group were superior to their counterparts in the FLEX group regarding near best corrected visual acuity, reading speed, and spectacle independence (all P < 0.05). CONCLUSION: ZMA00 and FLEX IOL implantation can provide excellent distant and intermediate visual acuity for patients with age-related cataract. ZMA00 IOL is superior to FLEX in terms of near visual acuity.

Improving the thermostability of a methyl parathion hydrolase by adding the ionic bond on protein surface.

The thermostability of the methyl parathion hydrolase (MPH_OCH) from Ochrobactrum sp. M231 was improved using site-directed mutagenesis. Two prolines (Pro76 and Pro78) located on the protein surface were selected for mutations after inspection of the sequence alignment of MPH_OCH and OPHC2, a thermostable organophosphorus hydrolase from Pseudomonas pseudoalcaligenes C2-1. The temperature of the double-point mutant (P76D/P78K) at which the mutant lost 50% of its activity (T50) was approximately 68 °C, which is higher than that of WT enzyme (64 °C), P76D (67 °C), and P78K (59 °C). Structural analysis of P76D/P78K indicated that the substituted residues (Asp76 and Lys78) could generate an ionic bond and increase the structural electrostatic energy, which could then increase the stability of the protein. These results also suggest that the thermal stability of proteins could be improved by adding the ionic bond on protein surface.

Regulation of cell division and growth in roots of Lactuca sativa L. seedlings by the Ent-Kaurene diterpenoid rabdosin B.

Rabdosin B, an ent-kaurene diterpenoid purified from the air-dried aerial parts of Isodon japonica (Burm.f) Hara var. galaucocalyx (maxin) Hara, showed a biphasic, dose-dependent effect on root growth and a strong inhibitory effect on root hair development in lettuce seedlings (Lactuca sativa L.). Lower concentrations of rabdosin B (20-80 microM) significantly promoted root growth, but its higher levels at 120-200 microM, by contrast, had inhibitory effects. Additionally, all tested concentrations (10-40 microM) inhibited root hair development of seedlings in a dose-dependent manner. Further investigations on the underlying mechanism revealed that the promotion effect of rabdosin B at the lower concentrations resulted from increasing the cell length in the mature region and enhancing the mitotic activity of meristematic cells in seedlings' root tips. In contrast, rabdosin B at higher concentrations inhibited root growth by affecting both cell length in the mature region and division of meristematic cells. Comet assay and cell cycle analysis demonstrated that the decrease of mitotic activity of root meristematic cells was due to DNA damage induced cell cycle retardation of the G(2) phase and S phase at different times.

A novel experimental heme oxygenase-1-targeted therapy for hormone-refractory prostate cancer.

Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormone-refractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decreased the HO-1 activity, oxidative stress, and activation of the mitogen-activated protein kinase-extracellular signal-regulated kinase/p38 kinase. This coincided with reduced cell proliferation, cell survival, and cell invasion in vitro, as well as inhibition of prostate tumor growth and lymph node and lung metastases in vivo. The effect of ho-1 silencing on these oncogenic features was mimicked by exposure of cells to a novel selective small-molecule HO-1 inhibitor referred to as OB-24. OB-24 selectively inhibited HO-1 activity in PCA cells, which correlated with a reduction of protein carbonylation and reactive oxygen species formation. Moreover, OB-24 significantly inhibited cell proliferation in vitro and tumor growth and lymph node/lung metastases in vivo. A potent synergistic activity was observed when OB-24 was combined with Taxol. Together, these results establish HO-1 as a potential therapeutic target for advanced PCA.

In vivo non-enzymatic repair of DNA oxidative damage by polyphenols.

The non-enzymatic repair of DNA oxidative damage can occur in a purely chemical system, but data show that it might also occur in cells. Human hepatoma cells (SMMC-7721) and human hepatocyte cells (LO2) were treated with 200microM H(2)O(2) for 30min to induce oxidative DNA damage quantified by amount of 8-OHdG and degree of DNA strand breaks, without inducing enzymatic repair. The dynamics of enzymatic repair activity quantified by unscheduled DNA synthesis, within 30min after removal of H(2)O(2) enzymatic repair mechanism has not been initiated. However, pre-incubation with low micromolar level polyphenols, quercetin or rutin can significantly attenuate DNA damage in both cell lines, indicating that the polyphenols did not work through an enzymatic mechanism. Unscheduled DNA synthesis after removal of H(2)O(2) was also markedly decreased by quercetin and rutin. Combined with our previous studies of fast reaction chemistry, the inhibitory effect of polyphenols have to be assigned to non-enzymatic repair mechanism rather than to enzymatic repair mechanism or antioxidant mechanism.

[Studies on the flavonoid constituents in herb of Eremosparton songoricum].

OBJECTIVE: To study the chemical constituents from Eremosparton songoricum. METHOD: The compounds were isolated with silica gel column chromatography and the structures of these compounds were elucidated by means of spectral analysis. RESULT: The seven compounds were identified as: 5,7,4'-trihydroxyflavone (apigenin) (I), 5-hydroxy-7,4'-dimethoxyflavone (II), 5,7-dihydroxy-3',4'-dimethoxyflavone (III), 5,7-dihydroxy-4'-methoxyflavone (acacetin) (IV), 5,7,4'-trihydroxy-3'-methoxyflavone (chrysoeriol) (V), 5,6,3',4'-tetrahydroxy-7-methoxyflavone (pedalitin) (VI) and 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-D-glucoside (flavogadorinin) (VII). CONCLUSION: These constituents were obtained from E. songoricum for the first time.

Protection against damaged DNA in the single cell by polyphenols.

The protective properties of seven polyphenols against hydrogen peroxide induced DNA damage in human peripheral blood lymphocytes (PBL) were studied using single cell micro-gel electrophoresis. Hydrogen peroxide causes a concentration-dependent increase in single cell DNA strand breakage in human PBL. Quercetin and 7,8-dihydroxy-4-methyl coumarin exhibited the strongest protection, significantly inhibiting 50 microM H2O2-induced DNA damage at a range of concentrations of 3.1-25 microM. Curcumin, resveratrol and vanillin protected against DNA damage induced by 50 microM H2O2 at a range of concentrations of 6.25-25 microM, but rutin and 7-hydroxy-4-methyl coumarin failed to provide any protection even at concentrations up to 50 microM. Quercetin, 7,8-dihydroxy-4-methyl coumarin, curcumin, resveratrol and vanillin are therefore effective in protection of human single cell DNA from oxidative attack.