Photo-induced synthesis of Axinastatin 3 analogs, the secondary structures and their in vitro antitumor activities.

Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for drug development. In an effort to identify what conformation could be accounting for the bioactive disparity of natural and synthetic cyclic peptides, some structurally-constrained analogs of cyclopeptide Axinastatin 3 were prepared by photo-induced single electron transfer (SET) reaction. Detailed stereochemistry study was performed by experimental electronic circular dichroism combined with theoretical calculations. Our study suggested that the cyclopeptide 1 with ßI-turn presented stronger antitumor activity comparing with those without such secondary structures. Moreover, a rare 'π helix unit' (compound 3) was realized because of the constrained cyclic structure, which could be considered an important research object for future study of unique helix secondary structures.

A Novel Photosensitizer 3¹,13¹-phenylhydrazine -Mppa (BPHM) and Its in Vitro Photodynamic Therapy against HeLa Cells.

Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM) was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa), and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT) against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT) assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm²). Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role.

[Transforming growth factor-ß1 induced cellular proliferation and collagen synthesis was mediated by reactive oxygen species in pulmonary fibroblasts].

OBJECTIVE: This study will explore whether reactive oxygen species (ROS) is involved in TGF-ß1-induced JNK activation, pulmonary fibroblast proliferation and collagen type I and III synthesis. METHODS: Pulmonary fibroblasts were randomly divided into control (0.4% serum) and TGF-ß1 (5 µg/L) groups to detect whether TGF-ß1 could induce pulmonary fibroblast proliferation, synthesis of collagen I and III, phosphorylated-JNK (p-JNK) and 8-OHdG (indicator of ROS); while in the part to explore whether NAC (N-acetyl-L-cysteine, antioxidants) has the inhibitory role in TGF-ß1-induced pulmonary fibroblast, it did control (0.4% serum), H2O2 (0.1 mmol/L, positive control), H2O2+NAC (10 mmol/L), TGF-ß1 (5 µg/L), TGF-ß1+NAC groups. Pulmonary fibroblast proliferation, 8-OHdG levels, expressions of JNK and collagen I and III were used by MTT assay, immunofluorescence and western blot respectively. RESULTS: In the experiments to detect the effect of TGF-ß1 on pulmonary fibroblasts, compared with control, TGF-ß1 significantly stimulated pulmonary fibroblast proliferation and increased collagen I and III protein, p-JNK and 8-OHdG levels. In the next experiments to explore whether NAC has the inhibitory role in TGF-ß1-induced pulmonary fibroblasts, compared with control, pulmonary fibroblast proliferation and the levels of collagen I and II, p-JNK, 8-OHdG were all significantly increased in H2O2 and TGF-ß1 groups; while these changes were markedly blocked with the treatment of NAC. CONCLUSION: TGF-ß1 induces pulmonary fibroblasts to generate ROS, which contributes to JNK activation and pulmonary fibroblast proliferation as well as collagen synthesis, while ROS inhibition suppresses this effet of TGF-ß1 in pulmonary fibroblasts.

Risk perception in the era of COVID-19 and related factors among nurses: A cross-sectional study.

AIM: Our study aimed at investigating the risk perception of nurses and related factors in the era of COVID-19 period. DESIGN: Cross-sectional study. METHODS: Four hundred and forty-two participants completed an online questionnaire relating to their risk perception on public health emergencies. Data were collected between 25 November 2020 and 1 December 2020. Kruskal-Wallis test, Mann-Whitney U test and Ordinal logistic regression analysis were used to examine factors impacting on risk perception. RESULTS: 65.2% of nurses' risk perception of COVID-19 was the moderate level even below the moderate level in the postperiod of COVID-19. Kruskal-Wallis test results indicated significant differences in gender, age, education status, working years, professional title, postlevel, COVID-19 contact experience, marital status and health status (p < 0.05). Ordinal logistic regression showed that gender, education status, professional title, work department, COVID-19 contact experience, character, health status and nursing work environment are associated with risk perception (p < 0.05). No Patient or Public Contribution.

γ-glutamylcysteine alleviates insulin resistance and hepatic steatosis by regulating adenylate cyclase and IGF-1R/IRS1/PI3K/Akt signaling pathways.

Type 2 diabetes mellitus (T2DM), a complex metabolism disease, which was characterized by metabolic disorders including hyperglycemia, has become a major health problem due to the increasing prevalence worldwide. γ-glutamylcysteine (γ-GC) as an immediate precursor of glutathione (GSH) was originally used for the treatment of sepsis, inflammation bowel disease, and senescence. Here, we evaluated the capacity of γ-GC on diabetes-related metabolic parameters in db/db mice and insulin resistance (IR) amelioration in cells induced by palmitic acid (PA). Our data suggested that γ-GC treatment decreased body weight, reduced adipose tissue size, ameliorated ectopic fat deposition in liver, increased the GSH content in liver, improved glucose control and other diabetes-related metabolic parameters in vivo. Moreover, in vitro experiments showed that γ-GC could maintain the balance of free fatty acids (FFAs) and glucose uptake through regulating the translocation of CD36 and GLUT4 from cytoplasm to plasma membrane. Furthermore, our finding also provided evidence that γ-GC could activate Akt not only via adenylate cyclase (AC)/cAMP/PI3K signaling pathway, but also via IGF-1R/IRS1/PI3K signaling pathway to improve IR and hepatic steatosis. Blocking either of two signaling pathways could not activate Akt activation induced by γ-GC. This unique characteristic ensures the important role of γ-GC in glucose metabolism. Collectively, these results suggested that γ-GC could serve as a candidate dipeptide for the treatment of T2DM and related chronic diabetic complications via activating AC and IGF-1R/IRS1/PI3K/Akt signaling pathways to regulate CD36 and GLUT4 trafficking.

Effective construction of a CuCo MOF@graphene functional electrocatalyst for hydrogen evolution reaction.

Electrochemical water splitting is considered a green and sustainable method of producing hydrogen energy. Herein, to pursue a highly efficient hydrogen evolution reaction, we fabricated high-performance electrocatalysts, by utilizing a bimetallic (Cu and Co) metal-organic framework to modify rGO through a one-step in situ approach. The synthesized CuCoOC@rGO presents a highly ordered structure with a defect-rich porous surface for the hydrogen evolution reaction (HER). Specifically, the appropriate adjustment of metal (Cu and Co), 1,3,5-benzenetricarboxylic acid (H3BTC), and rGO ratios leads to a well-defined morphology, which creates a defect-rich porous surface. Characterized by XRD, SEM, EDS, FT-IR spectroscopy, Raman spectroscopy, XPS, and BET, the morphology exposes more active sites, strong evidence for the promotion of electrocatalytic efficiency. Upon the analysis of the experimental data, the obtained CuCoOC@rGO catalyst exhibits excellent activity in alkaline media with a low overpotential of 120 mV at a current density of 10 mA cm-2, and a Tafel slope of 124 mV dec-1 for the hydrogen evolution reaction (HER). Guided by the structure-activity relationship, the superior HER activity of CuCoOC@rGO in alkaline electrolyte could originate from many sources, including: (1) as a self-supported substrate, CuCoOC@rGO not only leads to profitable electrical contact and mechanical stability but also firmly roots into the rGO without extra binders. (2) The highly ordered structure provides smooth ion and electron transport channels, which are conducive to electrolyte infiltration and gas release. (3) The abundance of defective pores on the surface of the nanoarrays, which offers more active sites for the catalytic process. This study provides new prospects for the rational design and fabrication of advanced hierarchical functional electrocatalysts for application in electrochemical energy devices.

Photo-induced synthesis, structure and in vitro bioactivity of a natural cyclic peptide Yunnanin A analog.

A cyclic analog of natural peptide Yunnanin A was synthesized via photoinduced single electron transfer reaction (SET) in the paper. The resulting compound exhibited potent bioactivity (with IC50 values 29.25 µg mL-1 against HepG-2 cell lines and 65.01 µg mL-1 against HeLa cell lines), but almost have no toxicity to normal cells (with IC50 values 203.25 µg mL-1 against L929 cell lines), which may be served as a potential antitumor drug for medical treatment. The spatial structure was examined by experimental electronic circular dichroism (ECD) and quantum chemistry calculations. Moreover, the theoretical study suggested that special intramolecular hydrogen bonds and γ, ß-turn secondary structures may be possible sources affecting cyclic peptide's bioactivity.

[Epidemiologic study on sleep apnea-hypopnea syndrome by home investigation in Chengde city].

OBJECTIVE: To investigate the prevalence of sleep apnea-hypopnea syndrome (SAHS) among adults aged over 30 yr in Chengde city of Hebei province. METHODS: 1 168 subjects (over 30 yr) were derived from a random sample of the population among the Shuangqiao district in Chengde city. All subjects were asked at home to answer questions about their snoring, daytime sleepiness, and habits of smoking and drinking. According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated according to AHI and ESS scores. RESULTS: 1 168 subjects (95.42%) answered the questions. The prevalence of snoring was 53.76%. The prevalence of moderate and severe snoring (>or= second degree) was 28.25%. The prevalence of snoring increased with age before the age of 70. The prevalence of snoring in males was significantly higher than that in females. Smoking and drinking groups were associated with a higher prevalence of snoring. The prevalence of snoring was higher in drivers (42.00%) than that in other populations. The estimated prevalence of SAHS according to both the AHI > 5 and the ESS >or= 9 was 4.63%. CONCLUSIONS: The estimated prevalence of SAHS among adults aged over 30 yr in Chengde city was 4.63%. It means that SAHS needs better understanding and more study.

[Effect of valproic acid against angiogenesis of Kasumi-1 xenograft tumor in nude mice].

This study was aimed to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t (8;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Ang1 and Ang2 were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Ang1 and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Ang1, Ang2 and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Ang1 from 0.360 ± 0.116 to 0.040 ± 0.008, Ang2 from 0.540 ± 0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Ang1, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascular density in xenograft tumor of nude mice (8.470 ± 0.300 vs 2.600 ± 0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.