Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

The pyrexia channel remodels egg-laying of Liriomyza huidobrensis in response to temperature change.

BACKGROUND: The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg-laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg-laying and temperature are still largely unknown. RESULTS: Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition-punching plasticity. We further show that this oviposition-punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down-regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg-laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg-laying amount. CONCLUSION: Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.

EZH2 serves as a promising therapeutic target for fibrosis.

Fibrosis affects the function of many organs and tissues, and its persistent development can lead to tissue sclerosis and cancer, even leading to death further. Recent studies suggested that enhancer of zeste homolog 2 (EZH2), a major regulator of epigenetic repression, played an important role in the occurrence and development of fibrosis through gene silencing or transcriptional activation. As the most studied and powerful pro-fibrotic cytokine closely related to EZH2, TGF-ß1 was primarily involved in the regulation of fibrosis along with the typical Smads and non-Smads signaling pathways. In addition, EZH2 inhibitors demonstrated inhibitory effects in several types of fibrosis. This review summarized the relationship underlying the action of EZH2, TGF-ß1/Smads, and TGF-ß1/non-Smads with fibrosis and described the research progress of EZH2 inhibitors in the treatment of fibrosis.

Explosion in the preparation of nanoparticles: monodisperse Ag inserted in 3D graphene sheets for the electrochemical detection of H2O2.

In this work, the smashing effect of explosives innovatively led to the preparation of nanoparticles. The energetic material 3,5-dinitrobenzoic acid (DNBA) was introduced as a ligand to coordinate with silver ions and connect graphene sheets via electrostatic attraction in the sol-gel process. Owing to the thermolysis of DNBA, the pore-formation of graphene sheets, thermal reduction of Ag+ and achievement of monodisperse Ag nanoparticles were realized simultaneously. The morphology and composition of the nanocomposites were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Then, the nanocomposite was used to construct a hydrogen peroxide (H2O2) sensor, which displayed excellent catalytic performance over a wide linear concentration range of 4 × 10-5 to 4 × 10-3 mM with a corresponding sensitivity of 72 µA mM-1 cm-2 and detection limit of 101.25 nM with a signal-to-noise ratio of 3.

Synthesis and anticancer activity of two highly water-soluble and ionic Pt(iv) complexes as prodrugs for Pt(ii) anticancer drugs.

Two new Pt(iv) complexes featuring mesylate as the outer sphere anion, cis,trans,cis-[PtCl2(OH2)2(NH3)2](CH3SO3)2 (SPt-1) and cis,trans,cis-[PtCl2(OH2)2(1R,2R-DACH)](CH3SO3)2 (SPt-2), were synthesized and characterized by elemental analysis, 1H and 13C NMR, IR, and ESI-MS. Both complexes have excellent water-solubility, high molar conductivity and good water stability. They exhibit an irreversible two-electron reduction event with the peak potentials (E p) for the processes being -0.40 V for SPt-1 and -0.52 V for SPt-2. The biological tests reveal that SPt-2 possesses high in vitro anticancer activity against three human cancer cell lines (HCT-116, A549 and MKN-1) and its overall anticancer activity is slightly greater than that of oxaliplatin, whereas SPt-1 is less active than cisplatin. Moreover, the antitumor efficacy of SPt-2 on human colon carcinoma HCT-116 xenografts in nude mice is also greater than that of oxaliplatin, suggesting that SPt-2 deserves further evaluation as a prodrug for oxaliplatin.

Discovery of 1,3,4-oxadiazole derivatives containing a bisamide moiety as a novel class of potential cardioprotective agents.

Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in the cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role of substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease the expression of cardiac hypertrophy and oxidative stress-related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.

Corrigendum to "miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation".

[This corrects the article DOI: 10.1155/2019/4530534.].

Determinants of personal exposure to fine particulate matter in the retired adults - Results of a panel study in two megacities, China.

This study aimed to investigate the relationship between outdoor, indoor, and personal PM2.5 exposure in the retired adults and explore the effects of potential determinants in two Chinese megacities. A longitudinal panel study was conducted in Nanjing (NJ) and Beijing (BJ), China, and thirty-three retired non-smoking adults aged 43-86 years were recruited in each city. Repeated measurements of outdoor-indoor-personal PM2.5 concentrations were measured for five consecutive 24-h periods during both heating and non-heating seasons using real-time and gravimetric methods. Time-activity and household characteristics were recorded. Mixed-effects models were applied to analyze the determinants of personal PM2.5 exposure. In total, 558 complete sets of collocated 24-h outdoor-indoor-personal PM2.5 concentrations were collected. The median 24-h personal PM2.5 exposure concentrations ranged from 43 to 79 µg/m3 across cities and seasons, which were significantly greater than their corresponding indoor levels (ranging from 36 to 68 µg/m3, p < 0.001), but significantly lower than outdoor levels (ranging from 43 to 95 µg/m3, p < 0.001). Indoor and outdoor PM2.5 concentrations were the strongest determinants of personal exposures in both cities and seasons, with RM2 ranging from 0.814 to 0.915 for indoor and from 0.698 to 0.844 for outdoor PM2.5 concentrations, respectively. The personal-outdoor regression slopes varied widely among seasons, with a pronounced effect in BJ (NHS: 0.618 ± 0.042; HS: 0.834 ± 0.023). Ventilation status, indoor PM2.5 sources, personal characteristics, and meteorological factors, were also found to influence personal exposure levels. The city and season-specific models developed here are able to account for 89%-93% of the variance in personal PM2.5 exposure. A LOOCV analysis showed an R2 (RMSE) of 0.80-0.90 (0.21-0.36), while a 10-fold CV analysis demonstrated a R2 (RMSE) of 0.83-0.90 (0.20-0.35). By incorporating potentially significant determinants of personal exposure, this modeling approach can improve the accuracy of personal PM2.5 exposure assessment in epidemiologic studies.

miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation.

Atherosclerosis (AS) is a chronic inflammatory disease, and macrophages play a key role in all phases of AS. Recent studies have shown that miR-221 is a biomarker for AS and stroke; however, the role and mechanism of miR-221 in AS are unclear. Herein, we found that miR-221 and NCoR levels were decreased in ox-LDL-treated THP-1-derived macrophages. In contrast, DNMT3b, IL-6, and TNF-α expression levels were increased under these conditions. Upregulation of miR-221 or NCoR could partially inhibit ox-LDL-induced IL-6 and TNF-α expression. Further studies showed that DNMT3b was a target of miR-221. DNMT3b inhibition also suppressed IL-6 and TNF-α expression and increased NCoR expression in the presence of ox-LDL. Moreover, DNMT3b was involved in ox-LDL-induced DNA methylation in the promoter region of NCoR. These findings suggest that miR-221 suppresses ox-LDL-induced inflammatory responses via suppressing DNMT3b-mediated DNA methylation in the promoter region of NCoR. These results provide a rationale for using intracellular miR-211 as a possible antiatherosclerotic target.

TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response.

Toll/IL-1R-domain-containing adaptor-inducing IFN-ß (TRIF) is an important adaptor for TLR3- and TLR4-mediated inflammatory signaling pathways. Recent studies have shown that TRIF plays a key role in vessel inflammation and atherosclerosis; however, the precise mechanisms are unclear. We investigated the mechanisms of the TRIF-regulated inflammatory response in RAW264.7 macrophages under oxidized low-density lipoprotein (ox-LDL) stimulation. Our data show that ox-LDL induces TRIF, miR-155, and BIC expression, activates the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways, and elevates the levels of IL-6 and TNF-α in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-α expression and inhibited the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways. Inhibition of ERK1/2 signaling also suppressed BIC and miR-155 expression. These findings suggest that TRIF plays an important role in regulating the ox-LDL-induced macrophage inflammatory response and that TRIF modulates the expression of BIC/miR-155 and the downstream SOCS1-STAT3-NF-κB signaling pathway via ERK1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.

[Method for continuous measurement of personal exposure to fine particulate matter].

OBJECTIVE: To develop a new accurate method for continuous measurement of personal exposure to fine particulate matter( PM_(2. 5) ) by integrating the advantage of both light scattering and gravimetric method. METHODS: The PM_(2. 5) concentrations were measured by both light scattering and gravimetric method simultaneously. The ratio of time-weighted average concentrations from gravimetric method to the responding values from light scattering method was calculated as coefficient of correction and used to calibrate the real-time PM_(2. 5) concentrations from light scattering method. RESULTS: The limit of detections( LOD) for 3, 10, 30 and 60 min time-weighted average concentrations of PM_(2. 5) were 4. 6, 4. 0, 3. 9 and 3. 7 µg/m~3, respectively. The precision( relativestandard deviation, RSD) was from 2. 1% to 9. 5%. The 30 min time-weighted average concentrations from this method were highly related to the results from TEOM method which was considered as reference method( Pearson r = 0. 934, P < 0. 001, n = 233), and no significantly bias between these two methods was detected by paired t test( P =0. 957). Zero drift was detected for 3 out of 10 devices with drift values in the range of- 5-- 3 µg/m~3 in the experiment of continuous 24 h monitoring conducted in the lab. And zero shift was also investigated in 7. 5%( 31 /412) field monitoring events, but most of the values shifted were within the range of- 3- 3 µg/m~3. The direction and scale of zero shift were not influenced by PM_(2. 5) concentrations. CONCLUSION: The developed method in this study that combines the advantages of both light-scattering and gravimetric method is validated to measure real-time concentrations of personal exposure to PM_(2. 5) .

Correction: Percutaneous Coronary Intervention after Fibrinolysis for ST-Segment Elevation Myocardial Infarction Patients: An Updated Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0141855.].

Percutaneous Coronary Intervention after Fibrinolysis for ST-Segment Elevation Myocardial Infarction Patients: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous coronary intervention (PCI), fibrinolysis and the combination of both methods are current therapeutic options for patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We searched PubMed, EMBASE, Google scholar and Cochrane Controlled Trials Register for randomized controlled trials (RCTs) evaluating the efficacy and safety of PCI after fibrinolysis within 24 hours, which was compared with primary PCI alone and ischemia-guided or delayed PCI. Meta-analysis was conducted using Review Manager 5.30 following the methods described by the Cochrane library. RESULTS: A total of 16 studies including 10,034 patients were enrolled. As compared with primary PCI alone group, the short-term mortality (5.8% vs 4.5%, RR 1.29, 95% confidence interval [CI] 1.00-1.65) and re-infarction rate (4.1% vs 2.7%, RR 1.46, 95%CI 1.05-2.03) were higher in the immediate PCI group (median/mean time ≤ 2 h after fibrinolysis). However, the short-term mortality and re-infarction rate showed no statistically significant differences in the early PCI group (2-24 hours after fibrinolysis). The rate of major bleeding events was higher both in the immediate PCI (6.3% vs 4.4%, RR 1.43, 95%CI 1.11-1.85) and the early PCI group (6.4% vs 4.4%, RR 1.46, 95%CI 1.03-2.06) as compared with primary PCI alone group. As compared with ischemia-guided or delayed PCI, early PCI was associated with significantly reduced re-infarction (2.4% vs 4.0%, RR 0.61, 95%CI 0.41-0.92) and recurrent ischemia (1.5% vs 5.3%, RR 0.29, 95%CI 0.12-0.70) at short-term. And the reduced re-infarction rate was also observed at long-term. CONCLUSIONS: Early PCI after fibrinolysis, with a relatively broader time for PCI preparation, can bring the similar effects with primary PCI alone and is better than ischemia-guided or delayed PCI in STEMI patients with symptom onset < 12 h who cannot receive timely PCI. However, immediate PCI after fibrinolysis is detrimental.

Nanoscale characterization of PM2.5 airborne pollutants reveals high adhesiveness and aggregation capability of soot particles.

In 2012 air pollutants were responsible of seven million human death worldwide, and among them particulate matter with an aerodynamic diameter of 2.5 micrometers or less (PM2.5) are the most hazardous because they are small enough to invade even the smallest airways and penetrate to the lungs. During the last decade the size, shape, composition, sources and effect of these particles on human health have been studied. However, the noxiousness of these particles not only relies on their chemical toxicity, but particle morphology and mechanical properties affect their thermodynamic behavior, which has notable impact on their biological activity. Therefore, correlating the physical, mechanical and chemical properties of PM2.5 airborne pollutants should be the first step to characterize their interaction with other bodies but, unfortunately, such analysis has never been reported before. In this work, we present the first nanomechanical characterization of the most abundant and universal groups of PM2.5 airborne pollutants and, by means of atomic force microscope (AFM) combined with other characterization tools, we observe that fluffy soot aggregates are the most sticky and unstable. Our experiments demonstrate that such particles show strong adhesiveness and aggregation, leading to a more diverse composition and compiling all possible toxic chemicals.

[A portable analyzer for determination of iodine in human urine].

A instrument based on principle of ion chromatography and amperometric detector for quick determination of iodine in urine are introduced in this paper, which covers from signal collection and treatment to data analysis. It presents the principle of hardware and software method to obtain the determination by using computer technology as well as the method of analysis of chromatogram. The instrument possess advantage of single, sensitive and simple. Both of tow stages of calibration curve for iodine 20-150 and 200-1500 micrograms/L respectively showed good linearity with r > 0.999. The detection limit of iodine was 10 micrograms/L(signal to noise ratio 3:1). The relative standard deviation was less than 5% (n = 4), The relative error of measuring urine reference material was less than 3%. Range of iodine in concentration 15 human urine samples by this method was 116.0-1079 micrograms/L.

[Photocatalytic oxidation of airborne VOCs on TiO2].

Titanium dioxide(TiO2) was used to catalyze the photolysis of benzene, xylene, n-heptane, methanol, acetone, ethylether, formaldehyde, trichloroethylene and perchloroethlene in air. The photolysis was carried out with a high pressure mercury lamp. The degradation rate of these VOCs was more than 80 percent in five minuts except formaldehyde. The effects of catalyst amount, different types of TiO2 catalyst and density of UV on the degradation rate of the VOCs were also studied.