The PLAUR signaling promotes chronic pruritus.

Chronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR+ sensory neurons responded to Serpin E1, resulting in enrichment of numerous itch- and inflammation-related genes and their protein release. PLAUR resides in TLR2+ neurons and Serpin E1 stimulus led to transcriptional upregulation of TLR2 and its co-signaling proteins. Agonists of TLR2 propagated itch-related gene transcription including BNP, OSM, and PAR2. OSM induced acute itch in mice and promoted G-CSF and IL-8 release from human keratinocytes. Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.

IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL-20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL-20 in AD remains unknown. Here, RNA-seq, Q-PCR, and immunocytochemistry were utilized to examine disease-driven changes of IL-20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD-models. Calcium imaging, knockdown and cytokine array were used to investigate IL-20-evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL-20-elicited sensations in vivo. We found that transcripts and protein of IL-20 were upregulated in skin from human AD and murine AD-like models. Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling. IL-20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD-related molecule release and transcription of itch-related genes. In sensory neurons, IL-20 application increased TLR2 transcripts, implicating a link between innate immune response and IL-20. In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.

Score test for missing at random or not under logistic missingness models.

Missing data are frequently encountered in various disciplines and can be divided into three categories: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). Valid statistical approaches to missing data depend crucially on correct identification of the underlying missingness mechanism. Although the problem of testing whether this mechanism is MCAR or MAR has been extensively studied, there has been very little research on testing MAR versus MNAR. A critical challenge that is faced when dealing with this problem is the issue of model identification under MNAR. In this paper, under a logistic model for the missing probability, we develop two score tests for the problem of whether the missingness mechanism is MAR or MNAR under a parametric model and a semiparametric location model on the regression function. The implementation of the score tests circumvents the identification issue as it requires only parameter estimation under the null MAR assumption. Our simulations and analysis of human immunodeficiency virus data show that the score tests have well-controlled type I errors and desirable powers.

MLP-mmWP: High-Precision Millimeter Wave Positioning Based on MLP-Mixer Neural Networks.

Millimeter wave (MMW) communication, noted for its merit of wide bandwidth and high-speed transmission, is also a competitive implementation of the Internet of Everything (IoE). In an always-connected world, mutual data transmission and localization are the primary issues, such as the application of MMW application in autonomous vehicles and intelligent robots. Recently, artificial intelligence technologies have been adopted for the issues in the MMW communication domain. In this paper, MLP-mmWP, a deep learning method, is proposed to localize the user with respect to MMW communication information. The proposed method employs seven sequences of beamformed fingerprints (BFFs) to estimate localization, which includes line-of-sight (LOS) and non-line-of-sight (NLOS) transmissions. As far as we know, MLP-mmWP is the first method to apply the MLP-Mixer neural network to the task of MMW positioning. Moreover, experimental results in a public dataset demonstrate that MLP-mmWP outperforms the existing state-of-the-art methods. Specifically, in a simulation area of 400 × 400 m2, the positioning mean absolute error is 1.78 m, and the 95th percentile prediction error is 3.96 m, representing improvements of 11.8% and 8.2%, respectively.

Metformin Can Be Safely Used in Patients Exposed to Contrast Media: A Systematic Review and Meta-Analysis.

BACKGROUND: There have been few studies published on the use of contrast media (CM) in metformin-treated patients. In this study, we conducted a systematic review and meta-analysis to investigate the relationship between metformin and contrast-induced acute kidney injury (CI-AKI). METHODS: A comprehensive search of the Medline, PubMed, Embase, and Web of Science databases for literature on associations between metformin use and CI-AKI incidence was conducted. The pooled odds ratio (OR), or relative risk, as well as the corresponding 95% confidence intervals (CIs), was calculated to assess the relationship between metformin and CI-AKI risk as well as the incidence of lactic acidosis (LA). RESULTS: In total, seven studies met our eligibility criteria on associations between metformin use and CI-AKI incidence, comprising 2,325 individuals, with 279 new cases of CI-AKI exposed to CM. The pooled analysis revealed no statistically significant increase in the risk of CI-AKI development in patients who used metformin continuously (random-effects OR: 1.15, 95% CI: 0.70-1.90, p = 0.57). No cases of LA that occurred during CM exposure were reported. CONCLUSION: Metformin can be safely used in patients with moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2) during CM exposure.

Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease.

BACKGROUND & AIMS: There are few in vitro models for studying the 3-dimensional interactions among different liver cell types during organogenesis or disease development. We aimed to generate hepatic organoids that comprise different parenchymal liver cell types and have structural features of the liver, using human pluripotent stem cells. METHODS: We cultured H1 human embryonic stem cells (WA-01, passage 27-40) and induced pluripotent stem cells (GM23338) with a series of chemically defined and serum-free media to induce formation of posterior foregut cells, which were differentiated in 3 dimensions into hepatic endoderm spheroids and stepwise into hepatoblast spheroids. Hepatoblast spheroids were reseeded in a high-throughput format and induced to form hepatic organoids; development of functional bile canaliculi was imaged live. Levels of albumin and apolipoprotein B were measured in cell culture supernatants using an enzyme-linked immunosorbent assay. Levels of gamma glutamyl transferase and alkaline phosphatase were measured in cholangiocytes. Organoids were incubated with troglitazone for varying periods and bile transport and accumulation were visualized by live-imaging microscopy. Organoids were incubated with oleic and palmitic acid, and formation of lipid droplets was visualized by staining. We compared gene expression profiles of organoids incubated with free fatty acids or without. We also compared gene expression profiles between liver tissue samples from patients with nonalcoholic steatohepatitis (NASH) versus without. We quantified hepatocyte and cholangiocyte populations in organoids using immunostaining and flow cytometry; cholangiocyte proliferation of cholangiocytes was measured. We compared the bile canaliculi network in the organoids incubated with versus without free fatty acids by live imaging. RESULTS: Cells in organoids differentiated into hepatocytes and cholangiocytes, based on the expression of albumin and cytokeratin 7. Hepatocytes were functional, based on secretion of albumin and apolipoprotein B and cytochrome P450 activity; cholangiocytes were functional, based on gamma glutamyl transferase and alkaline phosphatase activity and proliferative responses to secretin. The organoids organized a functional bile canaliculi system, which was disrupted by cholestasis-inducing drugs such as troglitazone. Organoids incubated with free fatty acids had gene expression signatures similar to those of liver tissues from patients with NASH. Incubation of organoids with free fatty acid-enriched media resulted in structural changes associated with nonalcoholic fatty liver disease, such as decay of bile canaliculi network and ductular reactions. CONCLUSIONS: We developed a hepatic organoid platform with human cells that can be used to model complex liver diseases, including NASH.

Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis.

The clinical significance and regulators of IL-13Rα2 in itch and atopic dermatitis (AD) remain unclear. To identify disease-driven regulatory circuits of IL-13Rα2, transcriptomic/pathological analysis was performed in skin from patients with AD, psoriasis, healthy subjects, and murine AD model. Functionality was investigated in sensory neurons, keratinocytes and animal model, by using knockdown (KD), calcium imaging, RNA-seq, cytokine arrays, pharmacological assays, and behavioural investigations. In our study, an upregulated IL-13Rα2 expression was revealed in skin of AD patients, but not psoriasis, in a disease activity-dependent manner. In cultured human keratinocytes, IL-13 increased IL-13Rα2 transcription levels, and this were downregulated by IL-13Rα1KD. IL-13Rα2KD reduced transcription levels of EDNRA, CCL20, CCL26. In contrast, sensory neuron-derived IL-13Rα2 was upregulated by TLR2 heterodimer agonists, Pam3CSK4 and FSL-1. In a mouse cheek model, pre-administration of Pam3CSK4 and FSL-1 enhanced IL-13-elicited scratching behaviour. Consistently, in cultured sensory neurons Pam3CSK4 enhanced IL-13-elicted calcium transients, increased number of responders, and orchestrated chemerin, CCL17 and CCL22 release. These release was inhibited by IL-13Rα2KD. Collectively, IL-13 regulates keratinocyte-derived IL-13Rα2 and TLR2 to modulate neuronal IL-13Rα2, thereby promoting neurogenic inflammation and exacerbating AD and itch. Thus, the cutaneous IL-13-IL-13Rα2 and neuronal TLR2-IL-13Rα2 pathway represent important targets to treat AD and itch.

Detection of Theileria spp. in ticks, sheep keds (Melophagus ovinus), and livestock in the eastern Tibetan Plateau, China.

Theileria species, with a broad geographic distribution, infect a wide range of both domestic and wild animals and are transmitted by ixodid ticks. Currently, there is no comprehensive report regarding the distribution of Theileria spp. in the eastern Tibetan Plateau, especially in Ganze Tibetan autonomous prefecture (153,700 km2) and Ngawa Tibetan and Qiang autonomous prefecture (84,242 km2) of Sichuan province, China. In this study, we collected blood samples from yaks (n = 144) (Bos grunniens), Tibetan sheep (n = 92), and Tibet horses (n = 142) in Ganze and Ngawa.Theileria sinensis, T. luwenshuni, and T. equi were the dominant Theileria species detected in yaks, Tibetan sheep, and horses with the total infection rates of 25.7% (37/144), 75.0% (69/92), and 51.4% (73/142), respectively. For ectoparasites, T. luwenshuni was the only Theileria species detected in sheep keds (Melophagus ovinus) with an infection rate of 30.8% (8/26). The total infection rates of T. sinensis in Haemaphysalis qinghaiensis, Dermacentor everestianus, and Rhipicephalus microplus were 34.6% (36/104), 34.0% (17/50), and 51.3% (58/113), respectively. Theileria spp., belonging to T. sergenti/buffeli/orientalis group, were only detected in R. microplus collected in Danba county of Ganze with a total infection rate of 39.9% (19/48). Our results provide important data of the epidemiology of Theileria spp. in livestock and ectoparasites and will assist with the implementation of measures to control theileriosis transmission in eastern Tibetan Plateau, China.

Detection of Echinococcus multilocularis in domestic dogs of Shiqu County in the summer herding.

Alveolar echinococcosis (AE) is one of the most serious parasitic zoonosis in Asia. Shiqu County is the most important endemic area of AE in China. Our primary objective is to find out the risk factors for Echinococcus multilocularis infection in domestic dogs in Shiqu County during the summer herding period. A total of 120 fecal samples were collected from 60 ranchers in October 2016. Nested PCR (nPCR) was performed to amplify regions of the mitochondrial12S rRNA gene of E. multilocularis. The results showed that the infection rates of AE in dogs from Qiwu, Yiniu, Changshaganma, Derongma, Mengyi, and Xiazha villages were 5, 5, 10, 20, 10, and 5%, respectively. It should be stressed that the infected dogs will shed eggs through feces and may have a habit of preying on rodents, the intermediate host of the parasite, and become re-infected. This investigation confirmed the presence of E. multilocularis infection in dogs in Shiqu and revealed the risk factors associated with the infection during summer herding.

A new two-step road extraction method in high resolution remote sensing images.

High-resolution remote sensing technology is an efficient and low-cost space-to-earth observation strategy, which can carry out simultaneous monitoring of large-scale areas. It has incomparable advantages over ground monitoring solutions. Traditional road extraction methods are mainly based on image processing techniques. These methods usually only use one or a few features of images, which is difficult to fully deal with the real situation of roads. This work proposes a two-steps network for the road extraction. First, we optimize a pix2pix model for image translation to obtain the required map style image. Images output by the optimized model is full of road features and can relief the occlusion issues. It can intuitively reflect information such as the position, shape and size of the road. After that, we propose a new FusionLinkNet model, which has a strong stability in the road information by fusing the DenseNet, ResNet and LinkNet. Experiments show that our accuracy and learning rate have been improved. The MIOU (Mean Intersection Over Union) value of the proposed model in road extraction is over 80% in both DeepGlobe and Massachusetts road dataset. The figures are available from https://github.com/jsit-luwei/training-dataset.

[Retracted] Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the certain of the cell proliferation assay data shown in Fig. 4C on p. 1444 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been submitted for publication [Shi N, Shan B, Song Y, Chu H and Qian L: Circular RNA circ­PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR­3680­3p in esophageal squamous cell carcinoma. J Cell Biochem 120: 10021­10030, 2019]. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 1439­1448, 2020; DOI: 10.3892/mmr.2020.10957].

Interobserver Variations in Target Delineation in Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma and its Impact on Target Dose Coverage.

BACKGROUND: To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. METHODS: Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose-volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. RESULTS: The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. CONCLUSIONS: The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.

[Effect of methylprednisolone on neurological behavior and the BDNF and NMDA receptor expression after traumatic spinal cord injury in rats].

OBJECTIVE: To study the effect of methylprednisolone on spinal cord injury rats' neural behavior and the expression of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartic acid (NMDA). METHODS: To establish rat model of spinal cord injury (SCI), the rats were randomly divided into sham operation group, SCI group and methylprednisolone group (n = 16 in each group). Eight rats were used for the behavioral assessment and BDNF measurement,the other eight animals was for the NMDA receptor test in each group. Within 8 h spinal cord contusion, methylprednisolone (50 mg/kg) was injected for methylprednisolone group, then after that the intramuscular injection of methylprednisolone was per day reduction in 10 mg/kg, till 5 days. By using immunohistochemical staining, the distribution of BDNF in the spinal cord and positive cell localization was observed and the number of positive cells were counted. The NMDA receptor affinity (Kd) and maximum binding amount (Bmax) were measured with [3H] MK-801 radioligand method, and the rat hind limb functional was also evaluated with BBB score analysis. RESULTS: Both the number of BDNF positive cells and the BBB score in methylprednisolone group was significant higher than that of SCI group; While increased receptor affinity (Kd) and decreased Bmax for NMDA receptor in methylprednisolone group was seen less than in SCI group (P < 0.05). CONCLUSION: Methylprednisolone can improve the function of rat hind limb, increase BDNF level and decreased NMDA receptor expression after spinal cord injury.

[Effect of gold belt on the BDNF and NMDA receptor expression and behaviour changes in rats following traumatic spinal cord injury].

OBJECTIVE: To study the effects of gold belt (GB), a Chinese Herbal, on behavioral changes and brain derived neutrophic factor (BDNF) expression and N-methyl-D-aspartic acid (NMDA) receptor level in rats subjected to spinal cord injury (SCI). METHODS: Adult male SD rats were randomly divided into three groups: (1) Sham group; (2) Spinal cord injury group (SCI group); (3) Spinal cord injury followed with gold belt treatment (gold belt 50 mg/(kg x d), intragastric gavage once daily for 7 days) group (GB group). The Basso, Beattie and Bresnahan (BBB) locomotor scale method was performed to evaluate the hindlimb motor function in the days 0, 3, 10 and 28. After 13 days, 8 rats in each group were treated with 1% sodium pentobarbital (30 mg/kg), myoloid tissue in T10 position was taken and stored in liquid nitrogen to detect NMDA receptor affinity and maximum binding amount (Bmax) with radioligand binding assay. After 28 days, rats were sacrificed and the spinal cords were harvested for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of the spinal cord. RESULTS: After spinal cord contusion, GB resulted in a significant increase on the number of BDNF positive neurons compared with traumatic group, and increased BBB score and decreased NMDA receptor were also found in GB group. Whereas decreased BDNF expression, NMDA receptor affininty (Kd) were observed in traumatic injury group. CONCLUSION: The gold belt treatment could effectively improve motor function, increase expression of BDNF, reduce the level of NMDA receptors in SCI rats. These data suggested that the gold belt played a role in the neuroplasticity after spinal cord injury.

[Dosimetric comparison of intensity-modulated arc radiotherapy and fixed beam dynamic intensity-modulated radiation therapy in nasopharyngeal carcinoma].

OBJECTIVE: To compare the dosimetric differences of dosiology between intensity-modulated arc radiotherapy (IMAT) and dynamic intensity-modulated radiation therapy (dIMRT) in nasopharyngeal carcinoma. METHODS: CT data from 25 patients treated in our radiotherapy center were selected randomly for this study. For each patient, the IMAT technique and the fixed beam dIMRT technique were accomplished by the simultaneously integrated boost. Dose volume histogram (DVH) data, isodose distribution, monitor units (MUs) and treatment time were compared in the two techniques. RESULTS: There was no significant difference between the IMAT and the dIMRT in dose received by 95% of target volumes (D(95)) (P>0.05). Overall, the mean dose (D(mean)), maximal dose (D(max)) and volume percentage receiving at least of 107% of the prescribed dose (V(107%)) of planning target volume (PTV) for the IMAT were increased slightly ,compared with the dlMRT (P<0.05). There were no significant differences in dosimetric indices of organs at risk (OARs) including spinal cord,optical nerves,lens and temporomandibular joints in the two techniques (P>0.05). Compared with the dlMRI, the D(max) of brain stem for the IMAT was increased slightly (P<0.05). Similar trends was observed for the D(mean) and dose received by 50% of volume (D(50)) of the left and right parotid glands (P<0.05). Healthy tissue (defined as the volume of the body minus PTV,B-P) irradiated from 800 cGy in the IMAT was higher, and that from 1200-4500 cGy was lower compared with the dlMRI (P<0.05).The average number of MUs was reduced by 62.7% per fraction, and the treatment time was on average reduced by 60.1% per fraction in the IMAT compared with the dlMRI. CONCLUSION: There is a slight difference in dosiology between the two radiotherapy techniques investigated, but they both meet the clinical requirement. Compared with the dIMRT, the IMAT delivers less irradiation to healthy tissue, uses fewer MUs and takes less time during radiotherapy for nasopharyngeal carcinoma.

Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma.

The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, lymphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC.

[Randomized controlled trial of integrated traditional Chinese and western medicine treatment for posthepatitic cirrhotic ascites: a systematic review].

OBJECTIVE: To research domestic general situation and quality of the clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine. METHODS: Chose CNKI, VIP, Wang fang and CBM as data source and searched the literature of the clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine which published officially from January 1980 to January 2010 and which received a Jaded score of 2 or greater to do a systematic evaluation, including the description of subjects, study design and methods, therapeutic efficacy and statistical methods. RESULTS: 136 articles in all met inclusion criteria and 58 articles which received a Jaded score of 2 or greater did this research. The main problems of domestic posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine in 30 years included: randomized controlled trial design was unreasonable, lack of blinding, lack of standardized criteria, the sample size was small and lack of specific estimation methods, lack of compliance, case off and withdraw, ignoring adverse reaction and the research of life quality. CONCLUSION: The clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine have a "personalized" and "diversity" character and the methods and standards of clinical research need to be improved.

Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Coronary heart disease (CHD) is the leading cause of human morbidity and mortality worldwide. MicroRNA (miRNA) profiling is an innovative method of identifying biomarkers for many diseases and may be a powerful tool in the diagnosis and treatment of CHD. The present study aimed to analyze the effects of miRNA (miR)­381 on the inflammatory damage of endothelial cells during CHD. A total of 21 patients with CHD and 21 healthy control patients were enrolled in this study. Reverse transcription­quantitative PCR, western blotting and immunofluorescence assays were conducted to examine the expression levels of miR­381, C­X­C chemokine receptor type 4 (CXCR4), Bcl­2, Bax, Cleaved­Caspases­3 and ­9, p38, ERK1/2 and JNK. Cell Counting Kit­8, EdU and flow cytometry experiments were performed to evaluate cell proliferation and apoptosis. An ELISA was adopted to determine the expressions of inflammatory factors (interleukins­8, ­6 and ­1ß, and tumor necrosis factor­α). In addition, a dual­luciferase reporter assay was used to determine the relationship between miR­381 and CXCR4. Decreased miR­381 expression and increased CXCR4 expression in the plasma were observed in the CHD group compared with the normal group, which indicated a negative relationship between miR­381 and CXCR4. Overexpression of miR­381 significantly promoted the proliferation and inhibited the apoptosis of oxidized low­density lipoprotein (OX­LDL)­induced human umbilical vein endothelial cells (HUVECs) through mitogen­activated protein kinase pathway by targeting and inhibiting CXCR4. Furthermore, overexpression of miR­381 reduced the release of inflammatory factors in OX­LDL­induced HUVECs. By contrast, reduced expression of miR­381 exerted the opposite effects, which were subsequently reversed by silencing CXCR4 expression. Results from the present study indicated that miR­381 was a CHD­related factor that may serve as a potential molecular target for CHD treatment.

APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells.

BACKGROUND/AIM: Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury. MATERIALS AND METHODS: Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells. RESULTS: Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p<0.05). ELA32 treatment inhibited iodixanol-induced mitochondrial ROS generation (p<0.01). Iodixanol-induced inflammatory cytokines TNFa and IL-6 and inflammatory genes Nrf2 and ICAM-1 were reduced by ELA32 treatment (p<0.01). Reduced Apela expression in iodixanol-treated cells was partially restored by ELA32 treatment (p<0.05). ELA32 treatment suppressed iodixanol-induced up-regulation of DNA damage-associated gene P-ATR and p-CHK1 as well as apoptosis-associated gene C-caspase 3 (p<0.05). CONCLUSION: Administration of iodinated contrast agent reduces Apela expression. ELA32 treatment reduces iodixanol-induced apoptosis, inflammatory response and mitochondrial and DNA damage in renal tubular epithelial cells.

Cryptococcal endocarditis of native valves without immunodeficiency or drug abuse: a case report.

Cryptococcal endocarditis has rarely been reported. Most patients with this condition are associated with risk factors, such as structural heart disease/valve replacement, immunodeficiency/immunosuppression or drug abuse. We report a case of cryptococcal endocarditis of the native valves without any risk factors. A 50-year-old Chinese man was admitted to hospital with fever for 1 month without any underlying heart disease, immunodeficiency, or drug use. He was diagnosed as having Cryptococcus neoformans infective endocarditis and was discharged after valve replacement surgery and long-term antifungal therapy.