MicroRNA-181 in cardiovascular disease: Emerging biomarkers and therapeutic targets.

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA-181 (miR-181) transcription and regulation and summarize recent findings on the roles of miR-181 family members as biomarkers or therapeutic targets in different cardiovascular-related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure. Lessons learned from these studies may provide new theoretical foundations for CVD.

Nanoplastics causes heart aging/myocardial cell senescence through the Ca2+/mtDNA/cGAS-STING signaling cascade.

BACKGROUND: Nanoplastics (NPs) are now a new class of pollutants widely present in the soil, atmosphere, freshwater and marine environments. Nanoplastics can rapidly penetrate cell membranes and accumulate in human tissues and organs, thus posing a potential threat to human health. The heart is the main power source of the body. But up to now, the toxicological effects of long-term exposure to nanoplastics on the heart has not been revealed yet. RESULTS: We evaluated the effects of long term exposure of nanoplastics on cardiac cell/tissue in vitro and in vivo model. Furthermore, we explored the molecular mechanism by which nanoplastics exposure causes myocardial cell senescence. Immunohistochemistry, indirect immunofluorescence and ELISA were performed to detect the effects of nanoplastics on heart aging. We found that nanoplastics were able to induce significant cardiac aging through a series of biochemical assays in vivo. In vitro, the effects of nanoplastics on cardiac cell were investigated, and found that nanoplastics were able to internalize into cardiomyocytes in time and dose-dependant manner. Further biochemical analysis showed that nanoplastics induces cardiomyocytes senescence by detecting a series of senescence marker molecules. Molecular mechanism research shows that nanoplastics may cause mitochondrial destabilization by inducing oxidative stress, which leads to the leakage of mtDNA from mitochondria into the cytoplasm, and then cytoplasm-localized mt-DNA activates the cGAS-STING signaling pathway and promotes inflammation response, ultimately inducing cardiomyocytes senescence. CONCLUSIONS: In this work, we found that nanoplastics exposure induces premature aging of heart. Current research also reveals the molecular mechanism by which nanoplastics induces cardiomyocyte senescence. This study laid the foundation for further studying the potential harm of nanoplastics exposure on heart.

HDAC Inhibitors Alleviate Uric Acid-Induced Vascular Endothelial Cell Injury by Way of the HDAC6/FGF21/PI3K/AKT Pathway.

ABSTRACT: Uric acid (UA) accumulation triggers endothelial dysfunction, oxidative stress, and inflammation. Histone deacetylase (HDAC) plays a vital role in regulating the pathological processes of various diseases. However, the influence of HDAC inhibitor on UA-induced vascular endothelial cell injury (VECI) remains undefined. Hence, this study aimed to investigate the effect of HDACs inhibition on UA-induced vascular endothelial cell dysfunction and its detailed mechanism. UA was used to induce human umbilical vein endothelial cell (HUVEC) injury. Meanwhile, potassium oxonate-induced and hypoxanthine-induced hyperuricemia mouse models were also constructed. A broad-spectrum HDAC inhibitor trichostatin A (TSA) or selective HDAC6 inhibitor TubastatinA (TubA) was given to HUVECs or mice to determine whether HDACs can affect UA-induced VECI. The results showed pretreatment of HUVECs with TSA or HDAC6 knockdown-attenuated UA-induced VECI and increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a. These effects could be reversed by FGF21 knockdown. In vivo, both TSA and TubA reduced inflammation and tissue injury while increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a in the aortic and renal tissues of hyperuricemia mice. Therefore, HDACs, especially HDAC6 inhibitor, alleviated UA-induced VECI through upregulating FGF21 expression and then activating the PI3K/AKT pathway. This suggests that HDAC6 may serve as a novel therapeutic target for treating UA-induced endothelial dysfunction.

Night shift work and depression among Chinese workers: the mediating role of sleep disturbances.

BACKGROUND: Depression is considered as a global problem. Recently, the prevalence of depression among night shift workers has been attracting people's attention. This study aims to explore the associations among night shift work, shift frequency and depression among Chinese workers and to explore whether sleep disturbances are a critical factor. METHODS: The cross-sectional survey consists of 787 autoworkers from a manufacturing plant in Fuzhou, China. Information about night shift work, shift frequency, depression, and sleep disturbances were collected from work records and responses to the Patient Health Questionnaire (PHQ-9) and the Pittsburgh Sleep Quality Index (PSQI). A mediation model was generated to examine relationship between night shift work, sleep disturbances, and depression. RESULTS: Our results found that night shift work, shift frequency, sleep disturbances, and depression had positive and significant relationships in a sample of Chinese workers. Night shift work, shift frequency and sleep disturbances were associated with an increased risk of depression among workers (OR: 4.23, 95% CI 2.55-7.00; 3.91, 2.31-6.63; 6.91, 4.40-10.86, respectively). Subsequent mediation analysis found that the association between night shift work and depression appeared to be partially mediated by sleep disturbances. CONCLUSION: These findings suggest that appropriate intervention and management strategies should be considered to alleviate the mental health burden of night shift workers.

lncRNA polymorphism affects the prognosis of gastric cancer.

BACKGROUND: Previous studies have found that lncRNA polymorphisms are associated with the prognosis of gastric cancer (GC), but the specific roles of many lncRNA polymorphism sites in gastric cancer are still unclear. Our study aims to deeply explore the relationship between genetic polymorphism of lncRNA and the prognosis of GC. METHODS: The genotypes of candidate SNP locus were detected by Sequenom Mass ARRAY SNP. We deeply analyzed the association of lncRNA polymorphisms with GC prognosis by univariate and multivariate Cox regression, stratified analysis, conjoint analysis, and log-rank test. RESULTS: We found that mutations at rs2579878 and rs10036719 loci reduced the risk of poor prognosis of GC. Stratified analysis showed that rs2795025, rs10036719, and rs12516079 polymorphisms were all associated with tumor prognosis. In addition, conjoint analyses showed that the interaction between these two polymorphic sites (rs2795025 and rs12516079) could increase the risk of poor prognosis. Multivariate analysis also found that the AG/AA genotype of rs10036719 and AG genotype of rs12516079 were independent prognostic factors. Moreover, the high expression of both CCDC26 and LINC02122 were shown to be associated with the poor survival status of GC patients. CONCLUSIONS: We find that the genetic polymorphism of lncRNA plays a role in the development of GC and is closely related to the survival time of patients. It could serve as a predictor of the prognosis of GC.

Open-Framework Zn Compound with Cationic-π Interaction: Photochromism and Benzene Series Detection.

Photochromic open-framework compounds are of potential application in detection/sensors. The issue of improving the detection limits has received much attention. We synthesized a new open-framework Zn compound, namely, compound 1 ([Zn(MQ)(IPA)Cl]·5H2O) (MQ = N-methyl-4,4'-bipyridinium, IPA = m-phthalic acid), which showed a 1D channel structure by a cationic-π interaction. It is noteworthy that this compound is an effective detector for aniline though luminescence emission, which exhibited unprecedented detection limits in photochromic open-framework compounds.

Photoswitching Bulk Quadratic Nonlinear-Optical Properties with Record Contrast in a Photochromic Semiconductor.

A high contrast of ∼67 times, exceeding those of all known photoswitching bulk quadratic nonlinear-optical materials, has been realized in a photochromic semiconductor, by the strategy of increasing electron-transfer efficiency and self-absorption.

[Analysis of prescription regularity of traditional Chinese medicine for colorectal cancer based on data mining].

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.

Apocynin protects endothelial cells from endoplasmic reticulum stress-induced apoptosis via IRE1α engagement.

Endoplasmic reticulum (ER) stress-induced endothelial cell (EC) apoptosis has been implicated in a variety of human diseases. In addition to being regarded as an NADPH oxidase (NOX) inhibitor, apocynin (APO) exhibits an anti-apoptotic effect in various cells. The present study aimed to identify the protective role of apocynin in ER stress-mediated EC apoptosis and the underlying mechanisms. We found that ER stress resulted in a significant increase in c-Jun N-terminal kinase phosphorylation, and elicited caspase 3 cleavage and apoptosis. However, apocynin obviously attenuated EC apoptosis and this effect was partly dependent on ER stress sensor inositol-requiring enzyme 1α (IRE1α). Importantly, apocynin upregulated IRE1α expression in both protein and mRNA levels and promoted the pro-survival XBP1 splicing. Our results suggest that apocynin protects ECs against ER stress-induced apoptosis via IRE1α involvement. These findings may provide a novel mechanistic explanation for the anti-apoptotic effect of apocynin in ER stress.

Role of moesin, Src, and ROS in advanced glycation end product-induced vascular endothelial dysfunction.

The disruption of endothelial integrity and the occurrence of angiogenesis in response to AGEs contribute greatly to micro- and macrovascular complications associated with DM. Among human dermal, brain, and retinal vascular ECs, activation of ERM, moesin, by phosphorylation of Thr-558 is involved in AGE-induced hyperpermeability and angiogenesis via the Rho and ROCK (Rho/ROCK) and p38 pathways. Src also plays an important role in AGE-induced endothelial barrier dysfunction by phosphorylating moesin, VE-cadherin, and FAK. Furthermore, recent studies have demonstrated that ROS serve as a key mediator of the AGE-induced endothelial response. ROS inhibition would greatly benefit ECs. This review focuses on the role of moesin in microvascular permeability and angiogenesis, and on the involvement of Src and ROS in endothelial barrier disruption.

N-Methyl-4-pyridinium Tetrazolate Zwitterion-Based Photochromic Materials.

N,N'-Disubstituted bipyridinium (viologen) and N-monosubstituted bipyridinium compounds are well known for their electron-transfer (ET) photochromic behavior. Their modification has exclusively focused on the N-substituents to date. For the first time, we have studied the photochromic behavior when one pyridyl ring of the bipyridinium is substituted with a multifunctional azole group, and have found that two new coordination compounds based on N-methyl-4-pyridinium tetrazolate (mptz) zwitterion, [Zn(mptz)2 Br2 ] (1) and [Cd3 (mptz)2 Cl6 ]n ⋅4n H2 O (2), exhibit typical ET photochromic behavior owing to photoinduced ET from halogen anion to the mptz ligand. This work demonstrates a new simple, neutral photoactive molecule with electron-accepting ability, which may act as a photoactive component for materials with potential photoswitching and photocatalysis applications.

Conductance Switch of a Bromoplumbate Bistable Semiconductor by Electron-Transfer Thermochromism.

Electron-transfer (redox) thermochromism was successfully used for switching the conductance of semiconductors, by introducing a thermally active organic component into an inorganic semiconducting framework. A moisture-resistant semiconductor {(MV)2 [Pb7 Br18 ]}n (MV2+ =methyl viologen cation) has been prepared through an in situ synthetic method for MV2+ . It features a rare 3D haloplumbate open framework and unprecedented electron-transfer thermochromic behavior in haloplumbates. The electrical conductivity of this compound dropped significantly after coloration and restored after decoloration, which was satisfactorily explained by valence band XPS and theoretical data. This work not only offers a new approach to modify electrical properties of semiconductors without altering components or structures, but may lead to the development of over-temperature color indicators, circuit overload protectors or photovoltaic materials.

Photochromism and Photomagnetism of a 3d-4f Hexacyanoferrate at Room Temperature.

Polycyanometallate compounds with both photochromism and photomagnetism have appealing applications in optical switches and memories, but such optical behaviors were essentially restricted to the cryogenic temperature. We realized, for the first time, the photochromism and photomagnetism of 3d-4f hexacyanoferrates at room temperature (RT) in [Eu(III)(18C6)(H2O)3]Fe(III)(CN)6·2H2O (18C6 = 18-crown-6). Photoinduced electron transfer (PET) from crown to Fe(III) yields long-lived charge-separated species at RT in air in the solid state and also weakens the magnetic susceptibility significantly. The PET mechanism and changing trend of photomagnetism differ significantly from those reported for known 3d-4f hexacyanoferrates. This work not only develops a new type of inorganic-organic hybrid photochromic material but opens a new avenue for RT photomagnetic polycyanometallate compounds.

Photochromic hybrid containing in situ-generated benzyl viologen and novel trinuclear [Bi3Cl14]5-: improved photoresponsive behavior by the π···π interactions and size effect of inorganic oligomer.

Two new member of (V)((2n+2)/2)[Bi(2n)Cl(8n+2)] series hybrids, (BzV)2[Bi2Cl10] (1) and (BzV)5[Bi3Cl14]2·(C6H5CH2)2O (2) (where BzV(2+) = N,N'-dibenzyl-4,4'-bipyridinium and (C6H5CH2)2O = dibenzyl ether) have been obtained, and compound 2 contains an unprecedented discrete trimer [Bi3Cl14](5-) counterion. The novel in situ-synthesized symmetric viologen cation with aromatic groups on both sides of 4,4'-bipy would provide more opportunities to create π···π interactions to optimize the photochromic property of the hybrid, and different bismuthated-halide oligomers enable us to discuss the size effect in this series of compounds. Both 1 and 2 are photochromic, and their photoresponsive rate is faster than that of reported viologen-metal halide hybrids. Experimental and theoretical data illustrated that the size of the inorganic oligomer can significantly influence the photoresponsive rate of the viologen dication, and the π···π interaction behaves as not only a powerful factor to stabilize the viologen monocation radical but also the second electron-transfer pathway, from a π-conjugated substituent to a viologen cation, for the photochromic process.

Design and syntheses of electron-transfer photochromic metal-organic complexes using nonphotochromic ligands: a model compound and the roles of its ligands.

The model compound [Zn(HCOO)2(4,4'-bipy)] (1; 4,4'-bipy = 4,4'-bipyridine) is selected in this work to demonstrate the effectiveness of our previously proposed design strategy for electron-transfer photochromic metal-organic complexes. The electron-transfer photochromic behavior of 1 has been discovered for the first time. Experimental and theoretical data illustrate that the photochromism of 1 can be attributed to the electron transfer from formato to 4,4'-bipy and the formation of a radical photoproduct. The electron transfer prefers to occur between formato and 4,4'-bipy, which are combined directly by the Zn(II) atoms. A high-contrast (up to 8.3 times) photoluminescence switch occurs during the photochromic process. The similarity of photochromic behaviors among 1 and its analogues as well as viologen compounds has also been found. Photochromic studies of this model compound indicate that new electron-transfer photochromic metal-organic complexes can be largely designed and synthesized by the rational assembly of nonphotochromic electron-donating and electron-accepting ligands.

Diagnostic value of magnetic resonance cholangiopancreatography for secondary common bile duct stones compared with laparoscopic trans-cystic common bile duct exploration.

BACKGROUND: The aim of this study was to evaluate the diagnostic potential of magnetic resonance cholangiopancreatography (MRCP) in preoperative patients with secondary common bile duct stones during the application of laparoscopic trans-cystic common bile duct exploration (LTCBDE). MATERIAL AND METHODS: The clinical records of 255 patients were retrospectively analyzed. All patients included in the study were examined by MRCP 3 days prior to LTCBDE. RESULTS: Secondary bile duct stones were detected in 220 patients using LTCBDE. Of the patients diagnosed by MRCP, 141 were true-positive, 28 were true-negative, 7 were false-positive and 79 were false-negative. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MRCP for secondary common bile duct stones were 64.09%, 80.00%, 66.27%, 95.27%, and 26.17%, respectively. When the cases with muddy stones were excluded, the outcomes were 80.41%, 79.41%, 69.23%, 94.44%, and 48.21%, respectively. When cases with stones <3 mm (inclusive) in diameter were excluded, the outcomes were 93.75%, 79.41%, 86.27%, 93.75%, and 65.85%, respectively. When cases with stones <5 mm (inclusive) in diameter were excluded, the outcomes were 93.10%, 79.41%, 89.26%, 92.05%, and 81.82%, respectively. CONCLUSIONS: The effectiveness of preoperative MRCP is overestimated for the diagnosis of secondary common bile duct stones, particularly for muddy and micro-stones.

Electron-transfer photochromism to switch bulk second-order nonlinear optical properties with high contrast.

The first bulk electron-transfer photochromic compound with intrinsic second-order nonlinear optical (NLO) photoswitching properties has been synthesized. This system employs an electron-transfer photoactive asymmetric viologen ligand coordinated to a zinc(II) center.

Improved photochromic properties on viologen-based inorganic-organic hybrids by using π-conjugated substituents as electron donors and stabilizers.

A series of inorganic-organic hybrid compounds L(2)(Bi(2)Cl(10)) (L = HMV(2+) = N-proton-N'-methyl-4,4'-bipyridinium for 1, L = HBzV(2+) = N-proton-N'-benzyl-4,4'-bipyridinium for 2, and L = HPeV(2+) = N-proton-N'-phenethyl-4,4'-bipyridinium for 3) have been successfully synthesized by an in situ solvothermal reaction. Compounds 1-3, with the same metal halide as anions but different asymmetric viologen molecules as cations, are ideal model compounds for investigating the detailed effect of different photochromically active molecules on the photochromic properties of the hybrids. Compound 1 shows no photochromic behavior, but compounds 2 and 3 possess photochromism and show a faster photoresponse rate than other reported viologen metal halide hybrids. Studies on the relationship between the structure and photochromic behavior clearly reveal that π-conjugated substituents could be used to improve the photoresponsibility and enrich the developed color efficiently and that the π···π interaction among organic components may not only be a powerful factor to stabilize the viologen monocation radical but also act as the second path of electron transfer from the π-conjugated substituent to the viologen cation for the photochromic process, which significantly influences the photochromic properties.

Zearalenone induces the senescence of cardiovascular cells in vitro and in vivo.

Zearalenone is a contaminant in food and feed products. It has been reported that zearalenone could lead to serious damage to health. So far, it is unclear whether zearalenone could lead to cardiovascular aging-related injury. For this, we assessed the effect of zearalenone on cardiovascular aging. Cardiomyocyte cell lines and primary coronary endothelial cells were used as two cell models in vitro experiments, and Western-blot, indirect immunofluorescence, and flow cytometry were performed to study the effect of zearalenone on cardiovascular aging. Experimental results indicated zearalenone treatment increased Sa-ß-gal positive cell ratio, and the expression of senescence markers (p16 and p21) was significantly upregulated. Additionally zearalenone upregulated the inflammation and oxidative stress in cardiovascular cells. Furthermore, the effect of zearalenone on cardiovascular aging was also evaluated in vivo, and the results indicated that zearalenone treatment also led to the aging of myocardial tissue. These findings suggest that zearalenone could lead to cardiovascular aging-related injury. Furthermore, we also preliminarily explored the potential effect of zeaxanthin (which is a powerful antioxidant) on zearalenone-caused aging-related damage in vitro cell model, and found that zeaxanthin could alleviate zearalenone-induced aging-related damage. Collectively, the most important finding of the current work is that zearalenone could lead to cardiovascular aging. Next in importance, we also found that zeaxanthin could partially alleviate zearalenone-induced cardiovascular aging in vitro, indicating that zeaxanthin can be used as a drug or functional food to treat cardiovascular damage caused by zearalenone.

Association of job stress, FK506 binding protein 51 (FKBP5) gene polymorphisms and their interaction with sleep disturbance.

Background: Sleep disturbance is an outcome of multiple factors including environmental and genetic influences. Job stress, a complex environmental factor, likely affects sleep quality, significantly reducing the quality of life of workers. Additionally, FK506 binding protein 51 (FKBP5) may be a pathogenic factor for sleep disturbance as it regulates hypothalamic-pituitary-adrenal (HPA) axis activity, where HPA axis has been found to be involved in the regulation mechanism of sleep and stress response. Objectives: The main aim of this study was to investigate the association between job stress and FKBP5 gene polymorphism as well as their interaction with sleep disturbance in Chinese workers; to date, these relationships have not been explored. Methods: This is a cross-sectional study. A total of 675 railway workers (53.8% male) completed a short Effort-Reward Imbalance questionnaire and the Pittsburgh Sleep Quality Index. The SNaPshot single nucleotide polymorphism (SNP) assay was carried out by screening for FKBP5 SNPs in every participant. Generalized multifactor dimensionality reduction (GMDR) was used to identify the strongest G×E interaction combination. Results: The findings showed that job stress was significantly associated with sleep disturbance; specifically, scores on the PSQI subscales (sleep disturbance, sleep medication, and daytime dysfunction) exhibited significant differences between the two job stress groups (X2 = 18.10, p = 0.01). Additionally, the FKBP5 SNP rs1360780-TT (adjusted odds ratio [AOR] = 4.98, 95% confidence interval [CI] = 2.80-8.84) and rs3800373-CC genotype (AOR = 2.06, CI = 1.10-3.86) were associated with an increased risk of sleep disturbance. Job stress and rs1360780 and rs3800373 variants showed a high-dimensional interaction with sleep disturbance as determined by the GMDR model. Conclusion: The FKBP5 gene may increase susceptibility to job stress and result in sleep disturbance, especially in the presence of negative work-related events. These findings contribute to the field of sleep disturbance prevention and treatment.