ABSTRACT
Two acylhydrazone based zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) were synthesized from 3-(1-(salicyloylhydrazono)ethyl) pyridine (HL). Single crystal X-ray structure analyses showed that complexes Zn1 and Zn2 have a zero-dimensional monomer or dimer structure. Antiproliferative activity studies revealed that Zn1 and Zn2 are both more effective against A549 cells than cisplatin. The results of the reactive oxygen species (ROS) generation assay on A549 cells showed that both Zn1 and Zn2 induced apoptosis through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of Zn1 and Zn2 on A549 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. What's more, the results of wound-healing assay showed that Zn1 and Zn2 could inhibit the migration of A549 cells. Western blot analysis further demonstrated that Zn1 and Zn2 induced cell apoptosis through the mitochondrial pathway, in which process, the expression level of cytochrome C, cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 proteins increased while pro-caspase 3 and pro-caspase 9 expression decreased. In vivo anticancer evaluation demonstrated that both Zn1 and Zn2 complexes effectively inhibited tumor growth without causing significant toxicity in systemic organs.
Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Coordination Complexes , Drug Screening Assays, Antitumor , Hydrazones , Lung Neoplasms , Zinc , Animals , Mice , A549 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Dose-Response Relationship, Drug , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Zinc/chemistry , Zinc/pharmacologyABSTRACT
Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.
Subject(s)
Carcinoma, Ovarian Epithelial , Ovarian Neoplasms , RNA, Circular , tau Proteins , Female , Humans , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/metabolism , Carcinoma, Ovarian Epithelial/pathology , tau Proteins/metabolism , tau Proteins/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Mice , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Animals , Disease Models, Animal , Cell Line, Tumor , Lipid Peroxidation/geneticsABSTRACT
High-efficiency electrocatalytic water splitting requires high intrinsic activity of catalysts and even more importantly favorable mass transfer. However, gas bubbles adhering to the surface of catalysts limit the re-expose of catalytic active sites to the electrolyte and reduce the catalytic activities. The efficient desorption of bubbles can be facilitated by a hierarchical multiscale structure of the electrode surface. Herein, we report an opened periodic three-dimensional electrode composed of iron (Fe)-cobalt (Co)-nickel (Ni) (oxy)hydroxide nanorods (NRs) grown in situ on a high aspect ratio nickel microcolumn array (NCA) for electrocatalytic water splitting. Compared with the flat nickel plate, the NCA not only increases the surface area for catalyst loading but also improves the wettability of the electrolyte on the electrode surface, exhibiting superhydrophilicity/superaerophobicity (the electrolyte and the bubble contact angles were about â¼0 and 163°, respectively), which accelerates the bubble evolution and desorption process. The X-ray photoelectron spectroscopy indicates that the synergy of Fe-Co-Ni could enhance the ratio of Co3+/Co2+ and Ni3+/Ni2+ and promote the electrocatalytic activity. Benefiting from the microstructure design and synergistic effects, the Co4Fe0.5Ni0.5OOH-NR@NCA electrode achieves a superior OER performance with an overpotential of 199 mV at 10 mA·cm-2.
ABSTRACT
Background: Pregnant women are a common group of people with tuberculosis,especially in patients infected with HIV at the same time. Antituberculosis drug prophylaxis is effective in reducing tuberculosis infection in pregnant women and fetuses after pregnancy, but its safety is still worthy of in-depth discussion. In this study, we conducted a systematic review and meta-analysis of reports on the use of antituberculosis drugs during pregnancy in recent years to provide evidence for clinical diagnosis and treatment. Methods: The PubMed, Embase, Web of Science databases, Ovid, and clinicaltrials.gov were searched. Search for clinical randomized controlled studies and cohort studies on the use of antituberculosis drugs during pregnancy published in the databases from January 2000 to September 2021 was performed using the Stata 16.0 software after screening qualified bodies of literature. Results: On the basis of the initial search of 408 articles, this study included a total of 8 articles and 2,563 patients after screening; meta-analysis results showed that preventive treatment with antituberculosis drugs did not increase the incidence of serious maternal adverse events [RR = 0.99, 95% CI (.88, 1.12), Z = -0.108, P = 0.914], did not increase drug hepatotoxicity [RR = 1.13, 95% CI (.9, 1.43), Z = 1.071, P = 0.284], did not increase the incidence of peripheral nerve disease [RR = 1.52, 95% CI (.85, 2.71), Z = 1.412, P = 0.158], did not increase maternal mortality [RR = 0.67, 95% CI (.27, 1.7), Z = -0.84, P = 0.401], and could significantly reduce adverse pregnancy outcomes [RR = 0.78, 95% CI (0.68, 0.89), Z = -3.581, P < 0.0001]. Discussion: The use of antituberculosis drugs for preventive treatment during pregnancy is safe and can obtain better pregnancy outcomes.
ABSTRACT
Visual lobe is a useful tool for predicting visual search performance. Up till now, no study has focused on dynamic visual lobe. This study developed a dynamic visual lobe measurement system (DVLMS) that could effectively map dynamic visual lobe and calculate visual lobe shape indices. The effects of display movement velocity on lobe shape indices were examined under four velocity conditions: 0, 4, 8 and 16 deg/s. In general, with the increase of display movement velocity, visual lobe area and perimeter became smaller, whereas lobe shape roundness, boundary smoothness, symmetry and regularity deteriorated. The elongation index was not affected by velocity. Regression analyses indicated that display movement velocity was important in determining dynamic visual lobe shape indices. Dynamic visual lobe provides another option for better understanding dynamic vision, in addition to dynamic visual acuity. Findings of this study can provide guidelines for analysing and designing dynamic visual tasks. Practitioner Summary: Dynamic visual lobe is important in reflecting the visual ability of searching for a moving target. We developed a dynamic visual lobe measurement system (DVLMS) and examined display movement velocity's effects on lobe shape. Findings revealed that velocity was a key factor affecting dynamic visual lobe shape indices.
Subject(s)
Pattern Recognition, Visual , Photic Stimulation/methods , Visual Fields , Visual Perception , Humans , Reproducibility of Results , Task Performance and Analysis , Young AdultABSTRACT
OBJECTIVE: To provide insight into diagnosis, treatment, and prevention of perioperative myocardial infarction (PMI). DESIGN: The authors retrospectively analyzed PMI characteristics in patients undergoing noncardiac surgery and identified risk factors for death. SETTING: An affiliated teaching hospital with about 1500 beds. PARTICIPANTS: The authors screened electronic medical records and retrospectively analyzed clinical data from 117,856 patients who underwent noncardiac surgery during the period from August 2003 through June 2011. INTERVENTIONS: Patients were divided into two groups based on survival at 30 days after PMI. MEASUREMENTS AND MAIN RESULTS: PMI was reported in 61 patients, for an overall incidence rate of 5.2 per 10,000. PMI incidence increased significantly with age, with a rate of 0.97 per 10,000 for the 45- to 60-year-old group, and increasing to a rate of 40.4 per 10,000 for the>75-year-old group (p<0.001). The mortality rate of non-PMI patients (n = 117,795) was 0.32%, whereas the mortality rate for the 61 PMI patients was 36.1% (p<0.001). PMI occurred acutely (within 48 to 72 hours of surgery) in the majority of patients (78.7%), and only 18% of these patients complained of chest pain. The majority of patients who suffered PMI had non-ST segment elevation acute myocardial infarction (78.7%). By multiple logistic regression analysis, lack of anticoagulation/antiplatelet therapy and cardiogenic shock were independent risk factors for death in PMI patients (p = 0.001 for both). CONCLUSIONS: PMI incidence increased significantly with advanced age. PMI increased mortality following non-cardiac surgery. The independent risk factors for death in PMI patients following noncardiac surgery were lack of anticoagulation/antiplatelet therapy and cardiogenic shock.