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Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Background: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used (for COPD) are not well evaluated as risk factors for increasing (or decreasing) dementia occurrence. We aimed to analyze the impact of different severities of COPD acute exacerbations (AEs) and different medications on the risk of suffering dementia in COPD patients.Method: This study was a 5-year follow-up of the Taiwanese government deidentified health-care database (from January 1, 2000, to December 31, 2010). The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Demographics, baseline comorbidities, medications (antibiotics, bronchodilators, corticosteroids), and the severity upon initial ED visit (only ED treatment, hospital admission, or ICU admission) were all considered confounding factors between the two groups.Results: Among the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatments obviously decreased the HRs, especially in those who received long-term (>1 month) treatment (HR=2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 COPD AE patients who initially visited the and ED, patients who required ICU admission (n=164, 4.7%) were at a very high risk of dementia occurrence (HR=11.05, 95% CI: 7.77-15.71).Conclusion: Long-term bronchodilator administration was associated with a decreased risk of suffering dementia. More importantly, patients who suffered COPD AEs and initially visited the ED and required ICU admission were at a very high risk of developing dementia.

Background. Diabetic cardiomyopathy is one of the cardiac complications in diabetes patients, eventually resulting in heart failure and increasing morbidity and mortality. Oxidative stress is a critical pathological feature in diabetic hearts, contributing to the development of DCM. Forskolin (FSK) was shown to reduce oxidative stress. This study was aimed at investigating the effects of FSK on diabetic hearts and the relevant molecular mechanisms. Methods. Streptozotocin- (STZ-) induced diabetes in mice was treated with FSK through intraperitoneal injection. Cardiac functions were evaluated by echocardiography. Hematoxylin-eosin and Masson trichrome staining was employed to determine heart morphological changes and cardiac fibrosis, respectively. Cardiac fibrosis-related markers were detected by western blot. Superoxide dismutase activity, reduced/oxidized glutathione ratio, and malondialdehyde concentration in left ventricles were determined using respective commercial kits. Results. Abnormal cardiac diastolic dysfunction and cardiac fibrosis were observed in diabetic hearts. FSK treatment significantly improved the cardiac diastolic function and attenuated the abnormal morphological change in diabetic hearts. Moreover, FSK treatment in diabetic mice decreased the expression of fibronectin, collagen I, TGF-β, and α-SMA and reduced myocardial fibrosis. Furthermore, we observed that FSK significantly blocked oxidative stress in diabetic hearts. Conclusions. Our study demonstrates that FSK protects against the development of DCM in STZ-induced diabetes in mice. Our study suggests that FSK might be a potential target for drug development in treating DCM.

Osteoarthritis (OA) is a multifactorial joint disease associated with the deterioration of chondrocytes and inflammation. Treatment of OA is only aimed at reducing pain and improving joint function. Recently, extracellular vesicles (EVs) secreted from stem cells have emerged as a cell regenerative tool in several degenerative diseases, including OA. We hypothesised that induced pluripotent stem cell (iPSC)-derived EVs would be beneficial for regenerating chondrocytes and OA therapy. Therefore, we aimed to investigate iPSC-EVs' effects on chondrocyte behaviour in an interleukin 1 beta (IL-1β)-inducedThe iPSC-EVs were isolated by sequential ultracentrifugation from a 48-h-incubated conditional medium of iPSC. The isolated iPSC-EVs were characterised by transmission electron microscopy, western blot analyses, and dynamic light scatter. The effects of iPSC-EVs on the viability of human primary chondrocytes and cell senescence were analysed. Premature senescence of cells was induced by long-term incubation with low doses of hydrogen peroxide. To investigate the therapeutic effect of iPSC-EVs on OA chondrocytesWe showed that iPSC-EVs significantly stimulated the proliferation of primary human chondrocytes and suppressed cell senescence by regulating the expression of p21 and collagen II. iPSC-EVs reduced matrix degradation enzymes and IL-6 expression and attenuated IL-1β-mediated cell death of chondrocytes. Furthermore, iPSC-EVs modulated macrophage polarisation, resulting in the rescue of damaged chondrocytes in an inflammatory microenvironment. In the rabbit ACLT model, the OA-like lesions, including inflammation, subchondral bone protrusion, and articular cartilage destruction, were ameliorated by iPSC-EV. A histopathological study consistently revealed that iPSC-EVs attenuated ACLT-mediated alteration of MMP13 and ADAMTS5 and collagen II expression.iPSC-EVs protected chondrocytes by enhancing cell proliferation, suppressing premature senescence, and maintaining homeostasis of collagen II synthesis and matrix degradation enzymes such as matrix metalloproteinases (MMPs) and ADAMTS5. iPSC-EVs also reduced cell death in IL-1β-mediated chondrocyte cell damage. In the rabbit ACLT-induced OA model, iPSC-EV injection reduced cartilage destruction, as indicated by the upregulation of collagen II and down-regulation of MMP13 and ADAMTS5. Overall, our results suggest that iPSC-EVs possess therapeutic potential and may be used as an OA treatment option.This study highlights the potential of iPSC-EVs as a therapeutic option for chondrocyte regeneration and OA treatment.

Background The initial episode of angioedema in children can be potential life-threatening due to the lack of prompt identification and treatment. We aimed to analyze the factors predicting the severity and outcomes of the first attack of acute angioedema in children. Methods This was a retrospective study with 406 children ( Result In total, 109 (26.8%) children had severe angioedema, and the majority of those children were male (65.1%). Most of the children were of preschool age (56.4%), and only 6.4% were adolescents. The co-occurrence of pyrexia or urticaria, etiologies of the angioedema related to medications or infections, the presence of respiratory symptoms, and a history of allergies (asthma, allergic rhinitis) were predictors of severe angioedema (all p p Conclusion The co-occurrence of pyrexia or urticaria, etiologies related to medications or infections, the presence of respiratory symptoms, and a history of allergies were predictors of severe angioedema. More importantly, short-term POU observation and prompt treatment might be benefit for patients who did not require hospital admission.

ObjectiveThe pros and cons of the head-up position (HUP) in cardiopulmonary resuscitation (CPR) have been controversial in previous studies. This study aims to clarify the effect of HUP CPR compared to supine position (SUP) CPR.MethodThree databases were comprehensively searched (PubMed, EMBASE and the Cochrane Library) for articles published from database inception to 10 May 2021. The primary outcome was cerebral perfusion pressure (CerPP). The secondary outcomes were mean intracranial pressure (ICP), mean artery pressure (MAP), coronary artery perfusion pressure (CoPP) and the return of spontaneous circulation (ROSC) rate.ResultA total of 7 studies including 138 animals were included. We found that CerPP (SMD, 1.58; 95% CI, 0.98–2.19; p 2 = 51%) and ICP (SMD, -3.59; 95% CI, -5.16– -2.02; p 2 = 87%) were decreased significantly in the HUP group. HUP had a similar MAP (SMD, -0.54; 95% CI, -1.75–0.66; p = 0.38; I2 = 87%) and ROSC rate (RR, 0.9; 95% CI, 0.31–2.60; p = 0.84; I2 = 65%) to SUP. In addition, there was an increased CoPP trend in HUP, but the difference was not statistically significant (SMD, 0.92; 95% CI, -0.24–2.08; p = 0.12; I2 = 84%)ConclusionThe HUP 30° in active compression-decompression CPR (ACD-CPR) with an impedance threshold device (ITD) can increase CerPP by significantly lowering ICP and maintaining MAP compared to SUP, and the effect is immediate and lasts the whole CPR duration. In addition, CoPP might also be increased compared to that with SUP.

The influence of the interface morphology of the SiC transition layer, including the shape, roughness and curvature, on the residual stresses of plasma sprayed ZrC-based coatings was simulated and analyzed in the current work. The results indicated that when the valleys and peaks of the interface were removed from the sine wave interface of the transition layer, the maximum values of radial compressive stress and axial tensile stress in the coating have transferred from the peak to the flat valley zone. An abrupt shear stress was found at the peaks and valleys, and a stress gradient was observed at the interface, making it easy to induce cracks perpendicular to the interface. Tensile stress concentration was located at the edge of the coating sample, where a large stress gradient was generated, resulting in easy cracking at the edge of the coating. The transition layer interface of the sine wave with valley-only morphology reduced the residual stress and improved the bonding strength of the interface, which was considered to be the optimal interface. The radial compressive stress and axial tensile stress in the coating increased with increasing interfacial curvature, with more significant changes observed for the axial tensile stress. This will lead to easy cracking and spalling of the coating, which was confirmed by experimental results. When the curvature of the interface is in the range of [0.2,0.3], the coating and substrate have good interface bonding strength.

Background/Objective: This study is a case–control study to explore risk and protective factors, including clinical data and bone mineral density (BMD), affecting vertebral body fragility fracture in elderly men and postmenopausal women. In addition, we investigate the effectiveness of lumbar spine BMD by quantitative computed tomography (QCT) in discriminating vertebral fragility fracture. Methods: In this case–control study, 52 males and 198 females with vertebral fragility fracture were compared with sex- and age-matched healthy controls to analyse the risk factors that may affect vertebral fragility fracture. The L1–L3 vertebral BMDs were measured by QCT. The difference in risk factors between fracture cases and controls were analysed using student t test and Mann–Whitney U test. The correlation between BMD, age, height and weight were analysed using univariate analysis. Multiple logistic regression analysis was used to study statistically significant indexes. The receiver operating characteristic curve was used to calculate the cut-off values for positive and negative predictive values of BMD for vertebral fracture discrimination. Results: In males, body weight and BMD were significantly different between the fracture group and the control group, whereas BMD was only weakly correlated with age (r = −0.234). In females, only BMD was significantly different between the fracture and control groups. BMD was weakly correlated with height (r = 0.133) and weight (r = 0.120) and was moderately correlated with age (r = −0.387). There was no correlation between BMD and the remaining variables in this study. In both men and women, the BMD (p = 0.000) was the independent protective factor against vertebral fracture. The cut-off values of vertebral BMD for fractures were 64.16 mg/cm3 for males and 55.58 mg/cm3 for females. QCT-measured BMD has a high positive predictive value and negative predictive value for discriminating vertebral fragility fracture across a range of BMD values. Conclusion: This study suggests that BMD is closely related to vertebral fragility fracture and that QCT is an effective technique to accurately discriminate vertebral fragility fracture. The translational potential of this article: The spine BMD measured by QCT is closely related to fracture, which may allow clinicians to more accurately discriminate which individuals are likely to experience vertebral fragility fracture. Keywords: Bone mineral density, Quantitative computed tomography, Vertebral fragility fracture

Cell based tissue engineering serves as a promising strategy for articular cartilage repair, which remains a challenge both for researchers and clinicians. The aim of this research was to assess the potential of autologous nasal chondrocytes (NCs) combined with alginate hydrogel as injectable constructs for rabbit articular cartilage repair. Autologous nasal chondrocytes were isolated from rabbit nasal septum, expanded either on monolayer or in 3D alginate hydrogel. In vitro, DNA quantification revealed that NCs can proliferate stable in 3D alginate matrix, but slower than that cultured in monolayer. Further, a higher synthesis rate of glycosaminoglycans (GAGs) was detected by GAG measurement in 3D alginate culture. Gene expression analysis at different time point (day 1, 7, 14) showed that 3D culture of NCs in alginate up-regulated chondrogenic markers (Col2A1, ACAN SOX9), meanwhile down-regulated dedifferentiation related gene (Col1A1). In vivo, autologous nasal chondrocytes combined with alginate hydrogel were used for repairing rabbit knee osteochondral defect (Alg + NC group). Histological staining indicated that Alg + NC group obtained superior and more hyaline-like repaired tissue both at 3 and 6 months after surgery. Mechanical analysis showed that the repaired tissue in the Alg + NC group possessed similar mechanical properties to the native cartilage. In conclusion, nasal chondrocytes appeared to be a very promising seed cell source for cartilage tissue engineering, and alginate hydrogel can serve as suitable delivery system.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Background. Since out-of-hospital cardiac arrest- (OHCA-) related dysfunction (ischemic/reperfusion injury and inflammatory response) might result in long-term impairment, we suspect that new-onset heart failure might be common in long-term survivors. However, these relationships had not been well addressed, and we aimed to analyze the impact of emergency interventions and patient characteristics on the risk of new-onset heart failure in patients with nontraumatic OHCA. Methods. The Taiwanese government healthcare database contains data for 49,101 nontraumatic OHCA adult patients from 2011-2012, which were analyzed in this study. Nontraumatic OHCA patients who survived to the intensive care unit (ICU) were included as the study group (n = 7,321). Matched patients (n = 21,963) were recruited as a comparison group. Patients with any history of heart failure or cardiac arrest were not included in either group. All patients were followed-up for 6 months for the identification of new-onset heart failure. Adjustments were made for demographics, age, emergency interventions, and comorbidities as potential risk factors. Results. In all, 3.84% (n = 281) of OHCA patients suffered new-onset heart failure, while only 1.24% (n = 272) of matched patients in the comparison group suffered new-onset heart failure. Strong risk factors for heart failure were age (60–75 years, HR: 11.4; 95% CI: 9–14.4), medical history (myocardial infarction, HR: 2.47; 95% CI: 2.05–2.98 and cardiomyopathy, HR: 2.94; 95% CI: 1.45–5.94), and comorbidities during hospitalization (ischemic heart disease, HR: 4.5; 95% CI: 3.46–5.86). Only extracorporeal membrane oxygenation (ECMO) decreased the risk of heart failure. Most (53.6%) heart failure events occurred within 60 days after OHCA. Conclusion. An age from 61 to 75 years, a history of myocardial infarction or cardiomyopathy, and ischemic heart disease or infection as comorbidities occurring during hospitalization were strong risk factors for new-onset heart failure in OHCA patients. However, ECMO could decrease this risk. More importantly, most heart failure events occurred within 60 days after OHCA.

Background Chronic pain and limited activities of daily living after spinal fracture may induce the occurrence of major depression (MD); however, risk factors regarding medications, surgical intervention, and severity of fracture are unclear. We aimed to analyze risk factors of MD development after spinal fracture. Methods This was a retrospective database study, using the health care database of the Taiwan government. We included 11,225 patients with new spinal fracture (study group), and 33,675 matched patients without fracture (comparison group). We respectively reviewed data of each participant for 3 years to assess the development of MD. The Cox proportional hazards model was used to determine the prevalence of MD, after adjusting for patient demographics, medications, surgical interventions, spinal cord involvement, and postfracture comorbidities. Results In total, 187 fracture patients (1.7%) and 281 nonfracture patients (0.8%) developed new-onset MD (hazard ratio [HR]:1.96, (95% confidence interval [CI]: 1.63–2.36)). Spinal cord involvement (HR: 2.96, 95% CI: 2.54–3.42) and postfracture comorbidities (HR: 3.51, 95% CI: 2.86–3.97) obviously increased the risk of MD. Conclusions Patients with spinal fracture (spinal cord involvement and postfracture comorbidities) were more likely to develop MD. Early surgical interventions (vertebroplasty) and medications (narcotics) may decrease the risk of MD.

Xun Yuan, Yi-Chuan Xiao, Gui-Ping Zhang, Ning Hou, Xiao-Qian Wu, Wen-Liang Chen, Jian-Dong Luo, Gen-Shui Zhang Department of Pharmacology, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14days after CQ (ip 60mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF. Keywords: chloroquine, diastolic function, HFpEF, autophagy, diabetic cardiomyopathy, type 1 diabetes mellitus

We used ANP and two-dimensional matrix as the analysis.It discusses the usage situation and effect of design strategy.It also proposes improvement directions for design strategies.The method is applied to the improvement of design strategy. With the intense competition of global market and the rapid technological advancement, the new product development becomes increasingly complicated, and relatively, designers face massive information that requires further integration. Design managers need an effective mechanism to understand the influence of design strategy application. Therefore, this study aims to use Analytic Network Process (ANP) and a two-dimensional matrix as the analysis tools, and discusses the usage situation and effect of design strategy, according to conformance quality and design quality. It also proposes improvement directions for design strategies. Based on the ANP results show that the order of top three items in design strategy are strengthening of market information collection and response capability (0.139), improvement of product quality level (0.135), and easy fabrication and maintenance (0.112). In addition, the ANP and the two-dimensional matrix model verified the use effect and improvement direction of design strategy. The ten design strategies can be classified into matured strategy, longitudinal improvement strategy, lateral improvement strategy, and two-way improvement strategy. The findings of this study can be provided to managers for reference in design strategy improvement.

β-Lactoglobulin (LG) is suspected to enhance or modulate human immune responses. Moreover, LG is also hypothesized to increase human cell proliferation. However, these potential functions of LG have not been directly or thoroughly addressed. In this study, we demonstrated that LG is a potent stimulator of cell proliferation using a hybridoma cell (a splenocyte fused with a myeloma cell) model. LG’s ability to promote cell proliferation was lost when the protein is denatured. To further investigate the influence of LG’s conformation on cell proliferation, we chemically modified LG by either carboxymethylation (CM) or acetylation and observed significantly reduced cell proliferation when the protein structure was altered. Furthermore, we proved that LG enhances cell proliferation via receptor-mediated membrane IgM receptor. These data indicated that nondenatured LG is the major component in milk that modulates cell proliferation. Collectively, our study showed that LG plays a key role in enhancing immune responses by promoting cell proliferation through IgM receptor.

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.

Electrochemical biosensors possess numerous desirable qualities for target detection, such as portability and ease of use, and are often considered for point-of-care (POC) development. Label-free affinity electrochemical biosensors constructed with semiconductor manufacturing technology (SMT)-produced electrodes and a streptavidin biomediator currently display the highest reproducibility, accuracy, and stability in modern biosensors. However, such biosensors still do not meet POC guidelines regarding these three characteristics. The purpose of this research was to resolve the limitations in reproducibility and accuracy caused by problems with production of the biosensors, with the aim of developing a platform capable of producing devices that exceed POC standards. SMT production settings were optimized and bioreceptor immobilization was improved through the use of a unique linker, producing a biosensor with exceptional reproducibility, impressive accuracy, and high stability. Importantly, the three characteristics of the sensors produced using the proposed platform all meet POC standards set by the Clinical and Laboratory Standards Institute (CLSI). This suggests possible approval of the biosensors for POC development. Furthermore, the detection range of the platform was demonstrated by constructing biosensors capable of detecting common POC targets, including circulating tumor cells (CTCs), DNA/RNA, and curcumin, and the devices were optimized for POC use. Overall, the platform developed in this study shows high potential for production of POC biosensors.

Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. (No 2508). We previously showed that Xyl-B promoted endothelial NO release and protected against atherosclerosis through the Akt/eNOS pathway. Vascular NO production regulates vasoconstriction in central and peripheral arteries and plays an important role in blood pressure control. In this study, we examined whether Xyl-B exerted an antihypertensive effect in a hypertensive rat model, and further explored the possible mechanisms underlying its antihypertensive action. Administration of Xyl-B (20 mg·kg(−1)·d(−1), ip, for 12 weeks) significantly decreased the systolic and diastolic blood pressure in a two-kidney, two-clip (2K2C) renovascular hypertensive rats. In endothelium-intact and endothelium-denuded thoracic aortic rings, pretreatment with Xyl-B (20 μmol/L) significantly suppressed phenylephrine (Phe)-induced contractions, suggesting that its vasorelaxant effect was attributed to both endothelial-dependent and endothelial-independent mechanisms. We used SNP, methylene blue (MB, guanylate cyclase inhibitor) and indomethacin (IMC, cyclooxygenase inhibitor) to examine which endothelial pathway was involved, and found that MB, but not IMC, reversed the inhibitory effects of Xyl-B on Phe-induced vasocontraction. Moreover, Xyl-B increased the endothelial NO bioactivity and smooth muscle cGMP level, revealing that the NO-sGC-cGMP pathway, rather than PGI(2), mediated the anti-hypertensive effect of Xyl-B. We further showed that Xyl-B significantly attenuated KCl-induced Ca(2+) entry in smooth muscle cells in vitro, which was supposed to be mediated by voltage-dependent Ca(2+) channels (VDCCs), and reduced ryanodine-induced aortic contractions, which may be associated with store-operated Ca(2+) entry (SOCE). Taken together, these findings demonstrate that Xyl-B exerts significant antihypertensive effects not only through the endothelial NO-sGC-cGMP pathway but also through smooth muscle calcium signaling, including VDCCs and SOCE.

Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21–23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA–mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.

MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.

Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. We previously demonstrated that pretreatment with Xyl-B exerted neuroprotective effects and attenuated hypoxic-ischemic brain injury in neonatal mice. In the present study we investigated the neuroprotective effects of pre- and post-treatment with Xyl-B in adult mice using a transient middle cerebral artery occlusion (tMCAO) model, and explored the underlying mechanisms. Adult male C57 mice were subjected to tMCAO surgery. For the pre-treatment, Xyl-B was given via multiple injections (12.5, 25, and 50 mg·kg−1·d−1, ip) 48 h, 24 h and 30 min before ischemia. For the post-treatment, a single dose of Xyl-B (50 mg/kg, ip) was injected at 0, 1 or 2 h after the onset of ischemia. The regional cerebral perfusion was monitored using a laser-Doppler flowmeter. TTC staining was performed to determine the brain infarction volume. We found that both pre-treatment with Xyl-B (50 mg/kg) and post-treatment with Xyl-B (50 mg/kg) significantly reduced the infarct volume, but had no significant hemodynamic effects. Treatment with Xyl-B also significantly alleviated the neurological deficits in tMCAO mice. Furthermore, treatment with Xyl-B significantly attenuated ROS overproduction in brain tissues; increased the MnSOD protein levels, suppressed TLR4, NF-κB and iNOS protein levels; and downregulated the mRNA levels of proinflammatory cytokines, including IL-1β, TNF-α, IL-6 and IFN-γ. Moreover, Xyl-B also protected blood-brain barrier integrity in tMCAO mice. In conclusion, Xyl-B administered within 2 h after the onset of stroke effectively protects against focal cerebral ischemia; the underlying mechanism may be related to suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway.

Background Emerging evidence indicates that plant miRNAs can present within human circulating system through dietary intake and regulate human gene expression. Hence we deduced that comestible plants miRNAs can be identified in the public available small RNA sequencing data sets. Results In this study, we identified abundant plant miRNAs sequences from 410 human plasma small RNA sequencing data sets. One particular plant miRNA miR2910, conserved in fruits and vegetables, was found to present in high relative amount in the plasma samples. This miRNA, with same 6mer and 7mer-A1 target seed sequences as hsa-miR-4259 and hsa-miR-4715-5p, was predicted to target human JAK-STAT signaling pathway gene SPRY4 and transcription regulation genes. Conclusions Through analysis of public available plasma small RNA sequencing data, we found the supporting evidence for the plant miRNAs cross kingdom RNAi within human circulating system. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3502-3) contains supplementary material, which is available to authorized users.

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity and the fourth leading malignancy and cause of cancer-related death in the male population of Taiwan. Most cases are detected at advanced stages, resulting in poor prognosis. Therefore, improved detection of early oral health disorders is indispensable. The involvement of oral bacteria in inflammation and their association with OSCC progression provide a feasible target for diagnosis. Due to the nature of oral neoplasms, the diagnosis of epithelial precursor lesions is relatively easy compared with that of other types of cancer. However, the transition from an epithelial precursor lesion to cancer is slow and requires further and continuous follow-up. In this study, we investigated microbiota differences between normal individuals, epithelial precursor lesion patients, and cancer patients with different lifestyle habits, such as betel chewing and smoking, using next-generation sequencing. Overall, the oral microbiome compositions of five genera, Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia, revealed significant differences between epithelial precursor lesion and cancer patients and correlated with their classification into two clusters. These composition changes might have the potential to constitute a biomarker to help in monitoring the oral carcinogenesis transition from epithelial precursor lesion to cancer.

Gastric cancer (GC) is the second leading cause of global cancer mortality. Most GC patients are diagnosed with advanced-stage disease and show extremely poor prognosis. All of the GC research has a common interest to search for the specific and sensitive biomarkers for early diagnosis of GC. Number of microRNAs play important role in GC. We carried out a systematic review of published miRNA profiling studies that compared the miRNA expression profiles between GC tissues and paired noncancerous gastric tissue. A vote-counting strategy was followed with the collection of information like total number of studies reporting differential expression of miRNA, total number of tissue samples used in the studies, direction of differential expression and fold change. A total of 352 differentially expressed microRNAs were reported in the 14 microRNA expression profiling studies that compared GC tissues with normal tissues with 120 microRNAs reported at least in two studies. In the group of consistently reported microRNAs, miR-21 was reported upregulated in 10 studies followed by miR-25, miR-92, and miR-223 upregulated in eight studies. MiR-375 and miR-148a were found downregulated in six and five studies, respectively, followed by miR-638 in four studies. MiR-107 and miR-103 were reported in nine and eight studies, respectively, but their expression were inconsistent. From this study, the most consistently reported upregulated microRNA was found to be miR-21. This systematic review study of human GC microRNA expression profiling studies would provide information on microRNAs with potential role as the biomarkers in gastric cancer.

A general and efficient palladium-catalyzed intermolecular direct C-2 alkenylation of indoles using oxygen as the oxidant has been developed. The reaction is of complete regio- and stereoselectivity. All products are E-isomers at the C-2-position with no Z-isomers and 3-substituted products were detected.

Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.