Search

Diabetes is characterized by changed homeostasis of blood glucose levels, which is associated with various complications, including cardiomyopathy, atherosclerosis, endothelial dysfunction, nephropathy, retinopathy and neuropathy. In recent years, accumulative evidence has demonstrated that circular RNAs are identified as a novel type of noncoding RNAs (ncRNAs) involving in the regulation of various physiological processes and pathologic conditions. Specifically, the emergence of complications response to diabetes is finely controlled by a complex gene regulatory network in which circular RNAs play a critical role. Recently, circular RNAs are emerging as messengers that could influence cellular functions under diabetic conditions. Dysregulation of circular RNAs has been closely linked to the pathophysiology of diabetes-related complications. In this review, we aimed to summarize the current progression and underlying mechanisms of circular RNA in the development of diabetes-related complications. We will also provide an overview of circular RNA-regulated cell communications in different types of cells that have been linked to diabetic complications. We anticipated that the completion of this review will provide potential clues for developing novel circular RNAs-based biomarkers or therapeutic targets for diabetes and its associated complications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery., Methods: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels., Results: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN)., Conclusion: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H 2 S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H 2 S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na 2 S 4 ), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H 2 S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na 2 S 4 and H 2 S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase β (IKKβ), followed by decreased phosphorylation of STAT3 and IKKβ. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-κB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (IκBα) induced by cisplatin, were also mitigated by both polysulfide and H 2 S. In mice, after treatment with polysulfide and H 2 S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H 2 S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKKβ and inhibiting NF-κB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H 2 S in chemotherapy-induced renal damage.

Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM + or BM - ) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM + patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM - group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM - patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker. © 2020 American Society for Bone and Mineral Research., (© 2020 American Society for Bone and Mineral Research.)

Searching for a target is faster in a repeated context compared to a new context, possibly because the learned contextual information guides visual attention to the target location (attentional guidance). Previous studies showed that switching the target location following learning, or having the target appear in one of multiple possible locations during learning, fails to produce search facilitation in repeated contexts. In this study, we re-examined whether the learning of an association between a distractor configuration context and a target is limited to one-to-one context-target associations. Visual search response times were facilitated even when a repeated context was associated with one of four possible target locations, provided the target locations were also shared by other repeated distractor contexts. These results suggest that contextual cueing may involve mechanisms other than attentional guidance by one-to-one context-target associations.

Humans are more proficient at processing visual display of body posture when the body is in upright orientation, compared to when inverted (inversion effect). Here we investigated whether extensive exposure or expertise on body posture recognition would affect the efficiency with which body-posture is processed. Using whole-body and piecemeal-body postures as stimuli, we performed two experiments to investigate whether body-posture recognition differed between two groups of participants: undergraduates majoring in physical education (PE) and those in other subjects (non-PE), respectively. These two groups differed significantly in the frequency and intensity of exercise per day and/or accumulated exercise time. In our experiments, following initial presentation of an image of a body posture, participants were shown the same or a different stimulus and were asked to report whether or not they had been previously shown the same image. The orientations of the body postures were also varied between trials. Our results showed that, in Experiment 1, for whole-body posture recognition, both the PE and non-PE groups showed a robust body-inversion effect in terms of both error rate and reaction time (RT), but the magnitude of the body-inversion effect in the RT measure was greater in the PE than the non-PE group. In Experiment 2, for piecemeal-body postures, both groups showed the inversion effect in terms of both error rate and RT measures and the PE group made fewer overall errors than the non-PE group. These cumulative results suggest that a superiority effect exists for PE participants compared with non-PE participants. Our results are generally consistent with the expertise hypothesis., (Copyright © 2020 Tao, Du, Li, He and Sun.)

Refrigeration is commonly used to extend the storage life of "Nanguo" pears, but fruit in long-term refrigeration is prone to peel browning, which is related to membrane lipid degradation. To determine the mechanism of membrane lipid degradation, we identified two R2R3-MYB transcription factors (TFs), PuMYB21 and PuMYB54, from "Nanguo" pears, which were notably expressed in response to cold stress and during the peel-browning process. The results from yeast one-hybrid, electrophoretic mobility shift, and transient expression assays indicated that both PuMYB21 and PuMYB54 directly bind to the promoter of PuPLDβ1 (a key enzyme catalyzing the hydrolysis of membrane phospholipids) and activate its expression, which probably enhances the degradation of membrane phospholipids and eventually results in peel browning. Moreover, the overexpression of PuMYB21 and PuMYB54 can greatly activate the transcription of endogenous PuPLDβ1 in both "Nanguo" pear fruits and calli, and their silencing can inhibit its transcription. Furthermore, yeast two-hybrid, bimolecular fluorescence complementation, and pull-down assays verified that PuMYB21 interacts with PuMYB54 to enhance the expression of PuPLDβ1 . In summary, we demonstrate that PuMYB21 and PuMYB54 may have roles in membrane lipid metabolism by directly binding to the downstream structural gene PuPLDβ1 during the low temperature-induced peel browning of "Nanguo" pears., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Purpose: To evaluate the clinical value of sialendoscopy in the treatment of Stensen's duct injury., Patients and Methods: A total of 5 patients with Stensen's duct injuries who had been treated from December 2017 to April 2019 were included in the present study. The operations were performed with the help of a sialendoscope. All patients were followed for 6 months., Results: The distal end of the ductal system was found precisely with the use of the sialendoscope, and the proximal end was identified by the location of the distal end. The end-to-end anastomosis was performed successfully. None of the patients complained of salivary gland fistula at the 6-month follow-up examination., Conclusions: The stumps of the ductal system could be precisely and effectively located with the help of a sialendoscope., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Gill, as the organ of fish to contact most directly with xenobiotics, suffered more threat. To evaluate the impact of arsenite (AsIII) on the gill of fish, we measured the antioxidative responses (superoxide dismutase (SOD) and catalase (CAT) activities) and oxidative damage (malondialdehyde (MDA) content), histological changes and mRNA transcriptional responses of zebrafish gill, after exposure to AsIII (0, 10, 50, 100, and 150 μg L -1 ) solutions for 28 days. We found that AsIII increased the activities of CAT by 46%-87%, decreased the activities of SOD and the contents of MDA by 19% and 21%-32%. Furthermore, CuZnSOD and MnSOD mRNA transcription levels were also inhibited, decreasing by 62%-82% and 70%-77%. Besides, ≥ 100 μg L -1 AsIII also caused histological changes (a loss of mucus and desquamation in the surface of the epithelial cells) on zebrafish gill. These results showed that low concentrations of AsIII influenced biochemical and physiological performances of fish gill, which probably aggravates the toxic effect of AsIII on fish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cardiovascular diseases are recognized to be a major cause of people morbidity and mortality. A host of stress signals contribute to the pathogenesis of cardiovascular disorders. Deficiency of hydrogen sulfide (H 2 S) or nitric oxide (NO) coordinately plays essential roles in the development of cardiovascular diseases. Recent studies have shown that interaction between the two gaseostransmitters, H 2 S and NO, may give rise to nitroxyl (HNO), one-electron-reduced product of NO. HNO is found to exhibit a variety of biological and pharmacological properties including positive inotropy and cardiovascular protective effects, etc. In this review, recent progresses regarding HNO generation, detection, biochemical and pharmacological functions are discussed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Dioscorea nipponica Makino is widely used in traditional Chinese medicine to treat gouty arthritis., Methods: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPARγ in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPARγ and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method., Results: Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum., Conclusion: RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.

Color generation based on strategically designed plasmonic nanostructures is a promising approach for display applications with unprecedented high-resolution. However, it is disadvantageous in that the optical response is fixed once the structure is determined. Therefore, obtaining high modulation depth with reversible optical properties while maintaining its fixed nanostructure is a great challenge in nanophotonics. In this work, dynamic color tuning and switching using tungsten trioxide (WO 3 ), a representative electrochromic material, are demonstrated with reflection-type and transmission-type optical devices. Thin WO 3 films incorporated in simple stacked configurations undergo dynamic color change by the adjustment of their dielectric constant through the electrochromic principle. A large resonance wavelength shift up to 107 nm under an electrochemical bias of 3.2 V could be achieved by the reflection-type device. For the transmission-type device, on/off switchable color pixels with improved purity are demonstrated of which transmittance is modulated by up to 4.04:1.

The present study investigated the chemical composition, antioxidant, antimicrobial, and anti-inflammatory activities of essential oil (EO) derived from the wild rhizomes of Atractylodes macrocephala Koidz. (AMA) growing in Qimen County (eastern China). GC/MS analysis identified fifteen compounds, representing 92.55 % of AMA EO. The major compounds were atractylone (39.22 %), β-eudesmol (27.70 %), thymol (5.74 %), hinesol (5.50 %), and 11-isopropylidenetricyclo[4.3.1.1(2,5)]undec-3-en-10-one (4.71 %). Ferricyanide reducing, 1,1-diphenyl-2-picyrlhydrazyl (DPPH) and 3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) scavenging assays revealed that AMA EO exhibited strong antioxidant capacities. Additionally, AMA EO showed inhibitory effects on growth of Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, and Bacillus subtilis, with the minimum inhibitory concentrations (MIC) ranging from 0.5 to 2.0 mg/mL. Treatments with AMA EO also significantly inhibited nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production in lipopolysaccharide-stimulated RAW264.7 cells, indicating anti-inflammatory activity of AMA EO. Furthermore, treatments with AMA EO decreased the transcriptional levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which might be the molecular mechanisms underlying its anti-inflammatory effects. Overall, these results provide a theoretical basis for further study and application of AMA EO in food and medicine products., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Endothelial cells are major constituents in the vasculature, and they act as important players in vascular homeostasis via secretion/release of vasodilators and vasoconstrictors. In healthy arteries, endothelial cells play a key role in the regulation of vascular tone, cellular adhesion, and angiogenesis. A shift in the functions of the blood vessels toward vasoconstriction, proinflammatory state, oxidative stress and deficiency of nitric oxide (NO) might lead to endothelial dysfunction, a key event implicated in the pathophysiology of cardiovascular metabolic diseases, including diabetes, atherosclerosis, arterial hypertension and pulmonary arterial hypertension (PAH). Thus, reversibility of endothelial dysfunction may be beneficial for maintaining vascular homeostasis. In recent years, accumulative evidence has documented that noncoding RNAs (ncRNAs) are critically involved in endothelial homeostasis. Specifically, long noncoding RNAs (lncRNAs) and circular RNAs are highly expressed in endothelial cells where they serve as important mediators in normal endothelial functions. Dysregulation of lncRNAs and circular RNAs has been tightly associated with hypertension-related endothelial dysfunction. In this review, we will summarize the current progression and underlying mechanisms of lncRNA and circular RNA in endothelial cell biology under hypertensive conditions. We will also highlight their potential as biomarkers or therapeutic targets for hypertension and its associated endothelial dysfunction.

Lead bioavailability in contaminated soils varies considerably depending on Pb speciation and sources of contamination. However, little information is available on bioavailability of Pb associated with different fractions. In this study, the Tessier sequential extraction was used to fractionate Pb in 3 contaminated soils to exchangeable (F1), carbonate-bound (F2), Fe/Mn oxides-bound (F3), organic-bound (F4), and residual fractions (F5). In addition, soil residues after F1-F2 extraction (F 345 ), F1-F3 extraction (F 45 ), and F1-F4 extraction (F 5 ) were measured for Pb relative bioavailability (RBA) using a mouse kidney model. Based on the mouse model, Pb-RBA in the soils was 44-93%, which decreased to 43-89%, 28-75%, and 15-68% in the F 345 , F 45 , and F 5 fractions, respectively. Based on Pb-RBA in the soil residues, Pb-RBA in different fractions was calculated based on a mass balance. The data showed that Pb-RBA was the highest (∼100%) in the exchangeable and carbonate fraction, and the lowest (15-68%) in the residual fraction. In addition, Pb in the first three fractions (F1-F3) contributed most (83-89%) to bioavailable Pb in contaminated soils. Our study shed light on oral bioavailability of Pb in contaminated soils of different fractions based on sequential extraction and provide important information for soil remediation., Competing Interests: Declaration of competing interest There is no conflict of interest from all authors., (Published by Elsevier Ltd.)

Stress-induced gastric mucosal lesion (SGML) is one of the most common visceral complications after trauma. Exploring the nervous mechanisms of SGML has become a research hotspot. Restraint water-immersion stress (RWIS) can induce GML and has been widely used to elucidate the nervous mechanisms of SGML. It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves. Many central nuclei, such as the dorsal motor nucleus of the vagus, nucleus of the solitary tract, supraoptic nucleus and paraventricular nucleus of the hypothalamus, mediodorsal nucleus of the thalamus, central nucleus of the amygdala and medial prefrontal cortex, are involved in the formation of SGML in varying degrees. Neurotransmitters/neuromodulators, such as nitric oxide, hydrogen sulfide, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, enkephalin, 5-hydroxytryptamine, acetylcholine, catecholamine, glutamate, γ-aminobutyric acid, oxytocin and arginine vasopressin, can participate in the regulation of stress. However, inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML, such as the involvement of different nuclei with the time of RWIS, the different levels of involvement of the sub-regions of the same nucleus, and the diverse signalling molecules, remain to be further elucidated., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Over the last several decades, hydrogen sulfide (H 2 S) has been found to exert multiple physiological functions in mammal systems. The endogenous production of H 2 S is primarily mediated by cystathione β-synthase (CBS), cystathione γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). These enzymes are widely expressed in the liver tissues and regulate hepatic functions by acting on various molecular targets., Aim of Review: In the present review, we will highlight the recent advancements in the cellular events triggered by H 2 S under liver diseases. The therapeutic effects of H 2 S donors on hepatic diseases will also be discussed., Key Scientific Concepts of Review: As a critical regulator of liver functions, H 2 S is critically involved in the etiology of various liver disorders, such as nonalcoholic steatohepatitis (NASH), hepatic fibrosis, hepatic ischemia/reperfusion (IR) injury, and liver cancer. Targeting H 2 S-producing enzymes may be a promising strategy for managing hepatic disorders., Competing Interests: The authors declared that there is no conflict of interest., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Reduced hepatic Na + /K + -ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of metabolism diseases. The present study was designed to investigate the potential roles of NKAα1 in hepatic gluconeogenesis and glycogenesis in both hepatocytes and obese diabetic mice. Methods : Insulin resistance was mimicked by glucosamine (GlcN) in either human hepatocellular carcinoma (HepG2) cells or primary mouse primary hepatocytes. Obese diabetic mice were induced by high-fat diet (HFD) feeding for 12 weeks. Results : We found that both NKA activity and NKAα1 protein level were downregulated in GlcN-treated hepatocytes and in the livers of obese diabetic mice. Pharmacological inhibition of NKA with ouabain worsened, while activation of NKAα1 with an antibody against an extracellular DR region of NKAα1 subunit (DR-Ab) prevented GlcN-induced increase in gluconeogenesis and decrease in glycogenesis. Likewise, the above results were also corroborated by the opposite effects of genetic knockout/overexpression of NKAα1 on both gluconeogenesis and glycogenesis. In obese diabetic mice, hepatic activation or overexpression of NKAα1 stimulated the PI3K/Akt pathway to suppress hyperglycemia and improve insulin resistance. More importantly, loss of NKA activities in NKAα1 +/- mice was associated with more susceptibility to insulin resistance following HFD feeding. Conclusions : Our findings suggest that NKAα1 is a physiological regulator of glucose homoeostasis and its DR-region is a novel target to treat hepatic insulin resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Remission criteria were proposed by Andreasen et al. for classifying patients with schizophrenia according to the severity of psychopathology. Up to the present time, there have been no cohort studies exploring the association between remission status and employment outcomes in patients with schizophrenia. The study explored whether symptomatic remission is significantly associated with employment outcomes in a two-year longitudinal study., Methods: All 525 stable patients with schizophrenia in the therapeutic community of a public mental hospital in Taiwan were recruited between 2013 and 2015. Employment outcomes, defined as the cumulative on-the-job duration (months/per year) and income (new Taiwan dollars, NT$/per year), were investigated at the end of 1- and 2-year follow-up periods after enrollment. For repeated measurements, linear mixed models were constructed to examine the association between symptomatic remission and employment outcomes after controlling for potential confounding variables including age, sex, education, type and daily dose of antipsychotics, cognitive function, psychosocial functioning and initial employment type., Results: The average age of patients was 51.8 years, and 65.3% were males. Among them, 124 patients (23.6%, 124/525) met the remission criteria at baseline. The linear mixed-model analysis showed that patients who had symptomatic remission were employed 0.8 of a month longer (p = 0.029) and earned NT$3250 more (p = 0.001) within 1 year than those who did not show symptomatic remission., Conclusion: Our study suggests that assessing symptomatic remission is a useful part of monitoring treatment effectiveness for schizophrenia, and all strategies targeting the bio-psycho-social domains to attain symptomatic remission are paramount to maintaining favorable employment outcomes.

Nitroxyl (HNO), one-electron reduced and protonated sibling of nitric oxide (NO), is a potential regulator of cardiovascular functions. It produces positive inotropic, lusitropic, myocardial anti-hypertrophic and vasodilator properties. Despite of these favorable actions, the significance and the possible mechanisms of HNO in diabetic hearts have yet to be fully elucidated. H9c2 cells or primary neonatal mouse cardiomyocytes were incubated with normal glucose (NG) or high glucose (HG). Male C57BL/6 mice received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Here, we demonstrated that the baseline fluorescence signals of HNO in H9c2 cells were reinforced by both HNO donor Angeli's salt (AS), and the mixture of hydrogen sulfide (H 2 S) donor sodium hydrogen sulfide (NaHS) and NO donor sodium nitroprusside (SNP), but decreased by HG. Pretreatment with AS significantly reduced HG-induced cell vitality injury, apoptosis, reactive oxygen species (ROS) generation, and hypertrophy in H9c2 cells. This effect was mediated by induction of caveolin-3 (Cav-3)/endothelial nitric oxide (NO) synthase (eNOS) complex. Disruption of Cav-3/eNOS by pharmacological manipulation or small interfering RNA (siRNA) abolished the protective effects of AS in HG-incubated H9c2 cells. In STZ-induced diabetic mice, administration of AS ameliorated the development of diabetic cardiomyopathy, as evidenced by improved cardiac function and reduced cardiac hypertrophy, apoptosis, oxidative stress and myocardial fibrosis without affecting hyperglycemia. This study shed light on how interaction of NO and H 2 S regulates cardiac pathology and provide new route to treat diabetic cardiomyopathy with HNO., Competing Interests: Declaration of competing interest The authors have no conflicts to declare., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the availability, prices and affordability of essential medicines in pediatric population across China, in the hope of improving rational use of medicines. Methods: A multicenter cross-sectional survey of medicine prices, availability and affordability was conducted in 17 provinces, municipalities and autonomous region across east, south-central part, west and north of China. Data on 42 medicines used in pediatric population, both original and generic, were collected in 55 public hospitals from May 26 to June 2, 2017. Availability was expressed as the percentage of hospitals with stock of the target medicine on the day of data collection,and median price ratio (MPR) was the ratio of price upon investigation to international reference. Based on national minimum daily wage, affordability represents the number of working days needed to earn the expense which covers a standard course using the target medicine. Statistical software SPSS 13.0 was applied for descriptive analysis of availability, MPR and affordability. Results: Mean Availability of original and generic medicine was 33% and 32%, with median MPR being 5.43 and 1.55. Among the 19 medicines with price information for both original and generic product, the median MPR was 7.73 and 2.04 respectively. Regarding the five medicines used to treat four common pediatric diseases (pneumonia,peptic ulcer, congenital hypothyroidism, refractory nephrotic syndrome), the affordability was 0.63 (0.16-6.17) d for generic medicine, and 1.03 (0.16-11.53) d for its original counterpart. Conclusions: The availability to both original and generic products of the 42 medicines used in pediatric population was low in China. The prices of generic medicines seem to be lower and affordability higher than those of original medicines. There is an urgent need to improve the availability and affordability of pediatric medicines.

The feasibility of laser-assisted treatments of medication-related osteonecrosis of the jaw (MRONJ) remains poorly understood, so we have therefore systematically evaluated their effectiveness. We made a comprehensive search of MEDLINE, Pubmed, and Embase to find randomised controlled trials, case-control studies, and prospective cohort studies that assessed them. We assessed the eligible studies in duplicate, and if possible conducted a meta-analysis. Ten studies with a low to high risk of bias met the inclusion criteria. We found that a comparison of pain scores before and after using visible and infrared GaAs laser in the low-level laser treatment based on the Numerical Pain Rating Scale (mean difference 4.28; 95% CI 3.62 to 4.93; p<0.00001), showed that there were significant differences in the amount of pain. The effectiveness of other laser-assisted treatments on the reduction of pain - for example, Er:YAG laser surgical treatment, and laser-assisted treatment plus platelet-rich plasma, and the effect of other techniques on wound healing of laser-assisted treatments, are uncertain. We found that the results of the studies that were deemed to be high-to-low quality and to have high-to-low statistical power suggested that there may be considerable clinical improvement in MRONJ by using laser-assisted treatment; we cautiously consider that low-level laser treatment may manage pain and symptoms in these patients. More randomised studies of good quality and with a low risk of bias are needed to test whether laser-assisted treatment should be a routine part of management of patients with MRONJ., (Copyright © 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Key Message: ZjICE2 works as a positive regulator in abiotic stress responses and ZjICE2 is a valuable genetic resource to improve abiotic stress tolerance in the molecular breeding program of Zoysia japonica. The basic helix-loop-helix (bHLH) family transcription factors (TFs) play an important role in response to biotic or abiotic stresses in plants. However, the functions of bHLH TFs in Zoysia japonica, one of the warm-season turfgrasses, remain poorly understood. Here, we identified ZjICE2 from Z. japonica, a novel MYC-type bHLH transcription factor that was closely related to ICE homologs in the phylogenetic tree, and its expression was regulated by various abiotic stresses. Transient expression of ZjICE2-GFP in onion epidermal cells revealed that ZjICE2 was a nuclear-localized protein. Also, ZjICE2 bound the MYC cis-element in the promoter of dehydration responsive element binding 1 of Z. japonica (ZjDREB1) using yeast one-hybrid assay. A phenotypic analysis showed that overexpression of the ZjICE2 in Arabidopsis enhanced tolerance to cold, drought, and salt stresses. The transgenic Arabidopsis and Z. japonica accumulated more transcripts of cold-responsive DREB/CBFs and their downstream genes than the wild type (WT) after cold treatment. Furthermore, the transgenic plants exhibited an enhanced Reactive oxygen species (ROS) scavenging ability, which resulted in an efficient maintenance of oxidant-antioxidant homeostasis. In addition, overexpression of the ZjICE2 in Z. japonica displayed intensive cold tolerance with increases in chlorophyll contents and photosynthetic efficiency. Our study suggests that ZjICE2 works as a positive regulator in abiotic stress responses and the ICE-DREB/CBFs response pathway involved in cold stress tolerance is also conserved in Z. japonica. These results provide a valuable genetic resource for the molecular breeding program especially for warm-season grasses as well as other leaf crop plants.

Objective: The purpose of this study was to analyze the relationship between von Willebrand factor (vWF) expression and lymph node metastasis or hemodynamics parameters in PTC. This work will provide a novel biomarker for the diagnosis of papillary thyroid carcinoma (PTC)., Patients and Methods: A total of 156 PTC patients were divided into metastatic and non-metastatic groups based on the presence or absence of lymph node metastasis. The Adler blood flow grading, color doppler flow imaging (CDFI), and blood flow index (PSV, PI, RI, AT) were measured and analyzed between the two groups. The expression of vWF was examined by immunocytochemical assay and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The function of vWF was investigated by methyl thiazolyl tetrazolium (MTT) and the transwell assays., Results: Both metastatic and non-metastatic groups with the major Adler grades as 0-1 had abundant blood flows. There was a significant difference in the rate of lymph node metastasis between Adler 2-3 and Adler 0-1. Moreover, the expression of vWF was found to be associated with lymph node metastasis or Adler blood flow grade in PTC. Significant differences in peak systolic velocity (PSV), systolic acceleration time (AT), and resistance index (RI) were detected in metastatic and non-metastatic groups. In addition, the upregulation of vWF was positively correlated with PSV, RI, and PI in PTC. Functionally, the knockdown of vWF inhibited the development of PTC by suppressing cell proliferation, migration, and invasion., Conclusions: Abnormal expression of vWF is closely related to lymph node metastasis and hemodynamics parameters in PTC patients. Furthermore, vWF plays an oncogene role in PTC progression.

Significance: As one-electron reduced molecule of nitric oxide (NO), nitroxyl (HNO) has gained enormous attention because of its novel physiological or pharmacological properties, ranging from cardiovascular protective actions to antitumoricidal effects. Recent Advances: HNO is emerging as a new entity with therapeutic advantages over its redox sibling, NO. The interests in the chemical, pharmacological, and biological characteristics of HNO have broadened our current understanding of its role in physiology and pathophysiology. Critical Issues: In particular, the experimental evidence suggests the therapeutic potential of HNO in tumor pharmacology, such as neuroblastoma, gastrointestinal tumor, ovarian, lung, and breast cancers. Indeed, HNO donors have been demonstrated to attenuate tumor proliferation and angiogenesis. Future Directions: In this review, the generation and detection of HNO are outlined, and the roles of HNO in cancer progression are further discussed. We anticipate that the completion of this review might give novel insights into the roles of HNO in cancer pharmacology and open up a novel field of cancer therapy based on HNO.

Lysophosphatidic acid (LPA), as a bioactive lipid, plays a variety of physiological and pathological roles via activating six types of G-protein-coupled LPA receptors (LPA1-6). Our preliminary study found that LPA1 is highly expressed in lung cancer tissues compared with paracancerous tissues, but the role of LPA1 in lung carcinoma is unclear. This study aimed to elucidate the association between LPA1 and lung tumour behaviour at the cellular and animal model levels. We found that LPA promoted the migration, proliferation and colony formation of a lung cancer cell line (A549). LPA1 and LPA3 are preferentially expressed in A549 cells, and both Ki16425 (LPA1 and LPA3 antagonist) and ono7300243 (LPA1 antagonist) completely blocked the LPA-induced actions. These results were further verified by experiments of the LPA1/3 overexpression and LPA1 knockdown A549 cells. Furthermore, LPA1 overexpression and knockdown A549 cells were used to assess the in vivo tumour-bearing animal model and the mechanism underlying LPA-induced actions. In the animal model, A549 cell-derived tumour volume was significantly increased by LPA1 overexpression and significantly decreased by LPA1 knockdown respectively, suggesting that LPA1 is a regulator of in vivo tumour formation. Our results also indicated that the LPA1/Gi/MAP kinase/NF-κB pathway is involved in LPA-induced oncogenic actions in A549 cells. Thus, targeting LPA1 may be a novel strategy for treating lung carcinoma., (Copyright © 2019. Published by Elsevier B.V.)

Salusin-β is abundantly expressed in many organs and tissues including heart, blood vessels, brain and kidneys. Recent studies have identified salusin-β as a bioactive peptide that contributes to various diseases, such as atherosclerosis, hypertension, diabetes and metabolic syndrome. However, the role of salusin-β in the pathogenesis of acute kidney injury (AKI) is largely unclear. In the present study, we investigated the roles of salusin-β in cisplatin or lipopolysaccharide (LPS)-induced renal injury. Herein, we found that salusin-β expression was upregulated in both renal tubular cells and kidney tissues induced by both cisplatin and LPS. In vitro, silencing of salusin-β diminished, whereas overexpression of salusin-β exaggerated the increased PKC phosphorylation, oxidative stress, histone γH2AX expression, p53 activation and apoptosis in either cisplatin or LPS-challenged renal tubular cells. More importantly, salusin-β overexpression-induced tubular cell apoptosis were abolished by using the PKC inhibitor Go 6976, reactive oxygen species (ROS) scavenger NAC, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin (Apo) or p53 inhibitor Pifithrin-α. In animals, blockade of salusin-β alleviated PKC phosphorylation, ROS accumulation, DNA damage, and p53 activation as well as renal dysfunction in mice after administration of cisplatin or LPS. Taken together, these results suggest that overexpressed salusin-β is deleterious in AKI by activation of the PKC/ROS signaling pathway, thereby priming renal tubular cells for apoptosis and death., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Endothelial cells are important constituents of blood vessels that play critical roles in cardiovascular homeostasis by regulating blood fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, and platelet aggregation. The normal vascular endothelium is taken as a gatekeeper of cardiovascular health, whereas abnormality of vascular endothelium is a major contributor to a plethora of cardiovascular ailments, such as atherosclerosis, aging, hypertension, obesity, and diabetes. Endothelial dysfunction is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and proinflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. The occurrence of endothelial dysfunction disrupts the endothelial barrier permeability that is a part of inflammatory response in the development of cardiovascular diseases. As such, abrogation of endothelial cell activation/inflammation is of clinical relevance. Recently, hydrogen sulfide (H 2 S), an entry as a gasotransmitter, exerts diverse biological effects through acting on various targeted signaling pathways. Within the cardiovascular system, the formation of H 2 S is detected in smooth muscle cells, vascular endothelial cells, and cardiomyocytes. Disrupted H 2 S bioavailability is postulated to be a new indicator for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we will summarize recent advances about the roles of H 2 S in endothelial cell homeostasis, especially under pathological conditions, and discuss its putative therapeutic applications in endothelial inflammation-associated cardiovascular disorders., (Copyright © 2020 Sun, Wu, Nie and Bian.)

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Age-related macular degeneration (AMD), a major eye degenerative disease, ultimately causes irreversible vision loss. Baicalin was identified to attenuate laser-induced chorodial neovascularization, indicating a therapeutic role in AMD. However, the exact mechanisms for baicalin in AMD remain unknown., Methods: MTT assay was performed to access the suitable concentration of baicalin or Aβ for treating ARPE-19 cells. CCK-8, morphology, and flow cytometry analysis were performed to evaluate cell viability and pyroptosis of baicalin in Aβ-envoked ARPE-19 cells. Quantitative real-time polymerase chain reaction and western blot analysis were subjected to measure the correlation between miR-223 and NLRP3. Luciferase reporter assay was performed to determine their direct relationship. Western blot analysis was subjected to determine pyroptosis-related proteins., Results: Baicalin inhibited Aβ-envoked pyroptosis in ARPE-19 cells. Mechanistically, baicalin significantly induced upregulation of miR-223 and downregulation of NLRP3, thus suppressing pyroptosis triggered by NLRP3 inflammasome signaling, yet such beneficial effects were reversed by miR-223 knockdown. Additionally, MCC950, a NLRP3 inhibitor, restored anti-pyroptosis activity of baicalin under miR-223 silencing., Conclusion: Baicalin alleviates intracellular pyroptosis and viability damage resulted from Aβ inducement in human retinal pigment epithelium cells via negative crosstalk of miR-223/NLRP3 inflammasome signaling, indicating that baicalin may be considered as a potential candidate for AMD therapy., (© 2019 S. Karger AG, Basel.)

Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.)

Congenital amusia, commonly known as tone deafness, is a lifelong impairment of music perception and production. It remains a question of debate whether the impairments in musical domain observed in congenital amusia are paralleled in other non-musical perceptual abilities. Using behavioral measures in two experiments, the current study explored face perception and memory in congenital amusics. Both congenital amusics and matched controls performed a face perception task (Experiment 1) and an old/novel object memory task (for both faces and houses, Experiment 2). The results showed that the congenital amusic group had significantly slower reaction times than that in matched control group when identifying whether two faces presented together were the same or different. For different face-pairs, the deficit was greater for upright faces compared with inverted faces. For object memory task, the congenital amusic group also showed worse memory performance than the control group. The results of the present study suggest that the impairment attributed to congenital amusia is not only limited to music, but also extends to visual perception and visual memory domain., Competing Interests: The authors have declared that no competing interests exist.

The autosomal short tandem repeat (STR) plays a unique role in population comparisons, phylogenetic reconstruction and migration history tracing. This study investigated the frequencies of 17 autosomal STR loci in the Han population from Wuxi, Eastern China, with the aim of expanding the available population information in human genetic databases and for forensic DNA analysis. The genetic polymorphisms of 17 STR loci were analysed in 5358 individuals of the Han population from Wuxi, Eastern China. Population comparisons including genetic distances, the neighbour-joining tree and multidimensional scaling plot were carried out between the Wuxi Han population and different ethnic groups. A total of 777 alleles at 17 autosomal STR loci were observed, with the corresponding allelic frequencies ranging from 0.0001-0.5210. The combined power of discrimination and exclusion for the 17 autosomal STR loci were 0.0000 and 0.000, respectively. Moreover, the phylogenetic analysis was performed between the Wuxi Han population and other relevant populations. The neighbour-joining tree and multidimensional scaling plot were generated based on Nei's standard genetic distance. Population comparisons indicated that the Wuxi Han population had the closest genetic relationship with the Hubei Han population, relative to the other populations, which mirrors the historical and geographical background of the populations compared.

ICE1 (Inducer of CBF Expression 1) is a regulator of cold-induced transcriptome, which plays an important role in plant cold response pathway. To enhance the cold tolerance of Zoysia japonica, one of the warm-season turfgrasses, it is helpful to understand the cold response mechanism in Zoysia japonica. We identified stress-responsive ZjICE1 from Zoysia japonica and characterized its function in cold stress. Our results showed that ZjICE1 shared the typical feature of ICE homolog proteins belonging to a nucleic protein. Transactivation activity assay revealed that ZjICE1 bound to the MYC cis-element in the ZjDREB1's promotor. The ZjICE1 overexpressed transgenic Arabidopsis showed enhanced tolerance to cold stress with an increases in SOD, POD, and free proline content and reduction in MDA content. They also induced the transcripts abundance of cold-responsive genes (CBF1, CBF2, CBF3, COR47A, KIN1, and RD29A) after cold treatment. These results suggest that ZjICE1 is a positive regulator in Zoysia japonica plant during cold stress and can be a useful gene for the molecular breeding program to develop the cold tolerant zoysiagrass. Furthermore, the ZjICE1 also conferred resistance to salt and drought stresses, providing the better understanding of the basic helix-loop-helix (bHLH) gene family in abiotic stress responses., (Copyright © 2019. Published by Elsevier B.V.)

A pot experiment was conducted to evaluate the growth response and vegetation restoration prospect of seedlings of five oak species for the phytoremediation of lead/zinc (Pb/Zn) mine tailings. Seedlings of Quercus imbricaria, Q. coccinea, Q. pagoda, Q. shumardii, Q. fabri were transplanted into pots containing Pb/Zn mine tailings to comparatively examine their biomass, root morphology, absorption and transfer characteristics of nutrient elements and heavy metals 30 months later. The results showed that all the seedlings could survive in the Pb/Zn tailings after 30 months. The biomass of Q. coccinea and Q. fabri decreased in Pb/Zn tailings compared with the control, while no significant difference were found for other three species. Compared with the control, root biomass was increased to some extent in Pb/Zn tailings except Q. coccinea. The lateral root morphological parameters were reduced only for Q. coccinea . Under heavy metal stress, nutrient concentrations of root and stem of oak seedlings did not change compared with the control. Generally, the concentrations of heavy metals in plant tissues were low, and the values of bioconcentration factor (BCF) and translocation factor (TF) were less than 1. Q. pagoda could accumulate more Cd, with concentrations of 22.4 and 15.1 mg·kg -1 in leaf and stem, respectively, and could translocate more Cd from root to shoot with TF of 2.3. Our results suggested that the seedlings of tested oak species could be used as the potential species for contaminated soil. Q. shumardii had the highest tole-rance with a low BCF and TF, implying that they were better potential candidates for afforestation and ecological restoration of mine tailings.

Immune dysfunction is implicated in the etiology of bipolar disorder. The single-nucleotide polymorphism rs17026688 in the gene encoding glutamate decarboxylase-like protein 1 (GADL1) has been found to be associated with lithium response in Han Chinese patients with bipolar I disorder (BDI). However, whether patients with GADL1 polymorphisms have different immunophenotypes is unknown. To address this issue, differences in the immune profiles based on analysis of peripheral blood mononuclear cells (PBMCs) were compared among BDI patients and healthy controls who lack or carry the T allele of rs17026688. BDI patients had significantly higher percentages of total T cells, CD4 + T cells, activated B cells, and monocytes than healthy controls, suggesting that immunologic imbalance might be involved in BDI development or progression. Treatment of BDI patients-derived PBMCs with lithium in vitro increased the percentage of CD14 + monocytes and dendritic cells, suggesting that lithium plays an immunomodulatory role in CD14 + monocytes and dendritic cells. Among BDI patients, non-T carriers had a significantly higher percentage of CD11b + /CD33 lo /HLA-DR - myeloid-derived suppressor cells than T carriers. Moreover, only T carriers exhibited differential sensitivity to lithium therapeutic use with respect to the percentage of myeloid cells. These findings suggest that rs17026688 polymorphisms in GADL1 are associated with immune dysfunction in BDI patients.

Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease., Competing Interests: None., (AJTR Copyright © 2019.)

To investigate the value of transvaginal three-dimensional (3D) power Doppler ultrasound in the diagnosis of benign and malignant endometrial diseases.A total of 144 patients with endometrial thickness ≥4 mm were enrolled. Endometrial thickness was measured by transvaginal 3D B-mode ultrasound, while blood signals were detected by 3D power Doppler ultrasound. Endometrial volume (EV), vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI) were calculated. All histopathological diagnoses of endometrium were obtained.There were 86 benign and 58 malignant cases. There were statistically significant differences between two groups in endometrial thickness [1.50 (1.30, 1.80) vs 2.30 (1.80, 3.20), P < .001], EV [10.62 (7.14, 17.36) vs 28.94 (9.59, 67.96), P < .001], VI [6.07 (3.61, 10.33) vs 12.01 (7.50, 19.87), P = .001], FI [27.42 (24.45, 31.33) vs 32.98 (30.22, 35.40), P < .001], and VFI [1.58 (0.92, 3.32) vs 4.28 (2.24, 6.41), P < 0.001]. Sensitivity and specificity of endometrial thickness were relatively high [endometrial thickness (86.2%, 76.1%), EV (48.3%, 97.7%), VI (72.4%, 69.8%), FI (72.4%, 74.4%), and VFI (72.4%, 74.4%)]. There was no significant difference in any parameters of the endometrium between different stages (Ia, Ib, II, and above) or phases (G1, G2, and G3) of Ia phase of endometrial cancer (all P > .05).Transvaginal 3D power Doppler ultrasound is valuable in the differentiating benign and malignant endometrial lesions.

Arsenic (As) present in water is a nonignorable environmental issue, even at low concentrations (≤150 μg L -1 ). To evaluate the toxic effect of low concentrations of As, zebrafish at early life stage were exposed to 0, 25, 50, 75, or 150 μg L -1 AsIII for 120 h. Our results indicated that low concentration of AsIII decreased zebrafish larvae's survival rate to 85%, 89% and 86% at 50, 75 and 150 μg L -1 . Furthermore, low concentrations of AsIII exposure caused oxidative stress (elevated superoxide dismutase (SOD) activity and influenced the mRNA transcriptional levels of Cu/ZnSOD and MnSOD) and damage (increased malondialdehyde levels). Meanwhile, zebrafish larvae regulated the mRNA transcription of metallothionein and heat shock protein 70 to alleviate toxicity caused by AsIII. These results revealed lower concentrations (≤150 μg L -1 ) of AsIII had a detriment effect on the survival of fish at early life stage, moreover, oxidative stress caused by AsIII posed potential risk for the zebrafish. This study provides novel insight into low concentration AsIII-induced toxicity in zebrafish., (Copyright © 2019. Published by Elsevier Ltd.)

Migration of vascular smooth muscle cell (VSMC) plays a critical role in the pathophysiology of hypertension and several other vascular diseases. Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a bioactive constituent from Curcuma longa, is commonly used as a spice, food additive or dietary pigment. It has several health benefits including antioxidant, anti-inflammatory and anticancer properties. This study examined the roles of curcumin in VSMC migration in hypertension and underlying mechanism. VSMC was isolated and prepared from thoracic aorta of Wistar-Kyoto rats and spontaneously hypertensive rats (SHR). VSMC migration was evaluated with Boyden chamber assay and wound-healing assay. Curcumin attenuated VSMC migration, inhibited nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression and reduced interleukin (IL)-1β concentration in VSMC of SHR, which were similar to the effects of NLRP3 knockdown on IL-1β concentration and VSMC migration. Curcumin inhibited NFκB activation in VSMC of SHR, which was similar to the effects of NFκB inhibitor BAY11-7082 on NFκB activation. In another in vitro model of rat VSMC migration, curcumin also inhibited angiotensin II-induced VSMC migration, NFκB activation, NLRP3 expression and IL-1β production. Intragastric administration of curcumin in SHR attenuated hypertension and reduced NFκB activation, NLRP3 and matrix metalloproteinase-9 expressions and aortic media thickness. These results indicate that curcumin inhibits VSMC migration via inhibiting NFκB-mediated NLRP3 expression in VSMC of SHR or in angiotensin II-treated VSMC. Curcumin attenuates hypertension, vascular inflammation and vascular remodeling in SHR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although various chemokines have pro-tumorigenic actions in cancers, the effects of CXCL16 remain controversial. The aim of this study was to investigate the molecular characteristics of CXCL16-expressing papillary thyroid cancers (PTCs). CXCL16 expressions were significantly higher in PTCs than benign or normal thyroid tissues. In the TCGA dataset for PTCs, a higher CXCL16 expression was associated with M2 macrophage- and angiogenesis-related genes and poor prognostic factors including a higher TNM staging and the BRAF V600E mutation. PTCs with a higher expression of 3-gene panel including CXCL16, AHNAK2, and THBS2 showed poor recurrence-free survivals than that of the lower expression group. Next, shCXCL16 was introduced into BHP10-3SCp cells to deplete the endogenous CXCL16, and then, the cells were subcutaneously injected to athymic mice. Tumors from the BHP10-3SCp shCXCL16 exhibited a delayed tumor growth with decreased numbers of ERG + endothelial cells and F4/80 + macrophages than those from the BHP10-3SCp control . CXCL16-related genes including AHNAK2 and THBS2 were downregulated in the tumors from the BHP10-3SCp shCXCL16 compared with that from the BHP10-3SCp control . In conclusion, a higher CXCL16 expression was associated with macrophage- and angiogenesis-related genes and aggressive phenotypes in PTC. Targeting CXCL16 may be a good therapeutic strategy for advanced thyroid cancer.

Activation of the renin-angiotensin system (RAS) contributes to the pathogenesis of cardiovascular diseases. Sodium potassium ATPase (NKA) expression and activity are often regulated by angiotensin II (Ang II). This study is aimed at investigating whether DR-Ab, an antibody against 4 th extracellular region of NKA, can protect Ang II-induced cardiomyocyte hypertrophy. Our results showed that Ang II treatment significantly reduced NKA activity and membrane expression. Pretreatment with DR-Ab preserved cell size in Ang II-induced cardiomyopathy by stabilizing the plasma membrane expression of NKA and restoring its activity. DR-Ab reduced intracellular ROS generation through inhibition of NADPH oxidase activity and protection of mitochondrial functions in Ang II-treated H9c2 cardiomyocytes. Pharmacological manipulation and Western blotting analysis demonstrated the cardioprotective effects were mediated by the activation of the AMPK/Sirt-3/PPAR γ signaling pathway. Taken together, our results suggest that dysfunction of NKA is an important mechanism for Ang II-induced cardiomyopathy and DR-Ab may be a novel and promising therapeutic approach to treat cardiomyocyte hypertrophy., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2019 Siping Xiong et al.)

Background: A study has shown that miR-423-5p is highly expressed in proliferative diabetic retinopathy. However, the exact biological functions and mechanisms of miR-423-5p in diabetic retinopathy (DR) progression are currently unclear. This study aimed to investigate the role of miR-423-5p in DR and the underlying mechanism., Results: Our data demonstrate that the expression of miR-423-5p is significantly increased in HG-induced RPE cells and DR patient plasma. Moreover, the overexpression of miR-423-5p exacerbates HG-induced apoptosis. Mechanistically, our results provide evidence that miR-423-5p directly targets TFF1. MiR-423-5p exerts its effect on HG-induced apoptosis in RPE cells through TFF1, and the NF-κB pathway is involved in the regulatory mechanism. Further analysis revealed that the transcription factor NFE2 regulates miR-423-5p promoter activity. In addition, NFE2 regulates the levels of TFF1 and NF-κB pathway-associated proteins by regulating the expression of miR-423-5p., Conclusion: The NFE2-miR-423-5p-TFF1 axis is a novel molecular mechanism and provides a new direction for the study and treatment of DR.

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H 2 S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H 2 S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H 2 S production by renal cells is reduced under disease states and H 2 S donors ameliorate kidney injury. Specifically, aberrant H 2 S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H 2 S in diabetic renal disease and the underlying mechanisms for the protective effects of H 2 S against diabetic renal damage. H 2 S may serve as fundamental strategies to treat diabetic kidney disease. These H 2 S treatment modalities include precursors for H 2 S synthesis, H 2 S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H 2 S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H 2 S in the kidney may be vital to translate H 2 S to be a novel therapy for diabetic renal disease., Competing Interests: The author declares no conflict of interest.

Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.

Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA B receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase-like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b + macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the 'T' allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)-mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder.

Human relaxin-2 reduces hepatic fibrosis in mice. However, the effects of relaxin-2 on hepatic steatosis and fibrosis in animals with non-alcoholic fatty liver disease (NAFLD) remain to be elucidated. C57BL/6 mice fed a high-fat diet (HFD) or methionine-choline-deficient (MCD) diet were randomly assigned to receive recombinant human relaxin-2 (25 or 75 μg/kg/day) or vehicle for 4 weeks. In HFD-fed mice, relaxin-2 decreased systemic insulin resistance and reduced body weight, epididymal fat mass and serum leptin and insulin concentrations. In livers of HFD-fed mice, relaxin-2 attenuated steatosis and increased phosphorylation of insulin receptor substrate-1, Akt and endothelial nitric oxide synthase (eNOS), and activated genes that regulate fatty acid oxidation and suppressed acetyl-CoA carboxylase. Relaxin-2 had no direct anti-steatotic effect on primary mouse hepatocytes, but S-nitroso-N-acetylpenicillamine attenuated palmitic acid-induced steatosis and activated genes regulating fatty acid oxidation in hepatocytes. In mice fed an MCD diet, relaxin-2 attenuated steatosis, inflammation and fibrosis. Relaxin-2 increased eNOS and Akt phosphorylation and transcript levels of cytochrome P450-4a10 and decreased acetyl-CoA carboxylase in MCD-fed mouse livers. Moreover, expression levels of Kupffer cell activation, hepatic stellate cell activation and hepatocyte apoptosis were decreased in MCD diet-fed mice receiving relaxin-2. In conclusion, relaxin-2 reduces hepatic steatosis by activating intrahepatic eNOS in HFD-fed mice and further attenuates liver fibrosis in MCD diet-fed mice. Therefore, human relaxin-2 is a potential therapeutic treatment for NAFLD.

Background/aims: To investigate the prevalence of abnormal central and peripheral ultra-wide-field (UWF) angiography findings, and their association with clinical features in acute Vogt-Koyanagi-Harada (VKH) disease., Methods: This retrospective, observational study included 26 eyes of 13 treatment-naïve patients with acute VKH disease who underwent UWF fluorescein angiography (FA). Sixteen eyes of eight patients also underwent UWF indocyanine green angiography (ICGA). A circle simulating the central 75° field was used to divide the acquired image into the central fundus area (CFA) and peripheral fundus area (PFA), in which the presence of six previously reported abnormal angiographic findings were analysed. Correlations between abnormal angiography findings in FA and clinical features were also investigated., Results: All eyes demonstrated more than one abnormal angiographic finding in both the CFA and PFA. UWF FA revealed three abnormal findings in the CFA versus the PFA: focal leakage (92.3% vs 76.9%); pooling with a dark rim (84.6% vs 53.8%); and retinal vascular leakage (0% vs 46.2%). UWF ICGA revealed three abnormal findings in the CFA versus the PFA: hypofluorescent dark dots (100% vs 100%); diffusely leaking fuzzy choroidal vessels (93.8% vs 75.0%); and late hypofluorescent patches (81.3% vs 31.3%). Pooling with a dark rim and retinal vascular leakage in the PFA were significantly associated with low initial visual acuity (p=0.03) and subfoveal choroidal thickness change ratio (p=0.04), respectively., Conclusion: Abnormal UWF angiography findings were frequently detected in the CFA and PFA. Such findings may be useful in evaluation and monitoring of VKH disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)