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ABSTRACTOur objective was to assess the impact of fortified high-dose docosahexaenoic acid (DHA) and arachidonic acid (ARA) in infant formula powders (IFs) on stability. We compared and evaluated the stability of IFs containing high and low doses of DHA and ARA over a 6-month storage period at 37°C. While most formulations showed minimal changes in unsaturated fatty acid content of during storage, significant losses of DHA and ARA were observed in some high-dose formulations. Furthermore, this study noted consistent trends in the changes of vitamin C and vitamin E across both formula groups. Notably, the high-dose group formulas exhibited a higher presence of volatile organic compounds (VOCs) during storage, along with a more pronounced increase in thiobarbituric acid-reactive substance values (TBARS). In conclusion, the inclusion of high doses of DHA and ARA in IFs may compromise their oxidative stability.

Abstract Background Providing sufficient and usable energy for the cell factory has long been a heated issue in biosynthesis as solar energy has never been rooted out from the strategy for improvement, and turning Escherichia coli (E. coli) into a phototrophic host has multiple captivating qualities for biosynthesis. In this study, β-carotene was a stable compound for production in E. coli with the expression of four enzymes (CrtE, CrtB, CrtI, CrtY) for production due to its light-harvesting feature as an antenna pigment and as an antioxidant and important precursor for human health. The expression of Gloeobacter rhodopsin (GR) in microbial organisms was proved to have potential for application. Results The expression of fusion protein, GR-GFP, in E. coli showed visible GFP signal under fluorescent microscopy, and its in vivo proton pumping activity signal can be detected in induced photocurrent by electrodes on the chip under intervals of illumination. To assess the phototrophic synthesis ability of the host strain compared to wild-type and vector control strain in chemostat batch with illumination, the expression of red fluorescent protein (RFP) as a target protein showed its yield improvement in protein assay and also reflected its early dominance in RFP fluorescence signal during the incubation, whereas the synthesis of β-carotene also showed yield increase by 1.36-fold and 2.32-fold compared with its wildtype and vector control strain. To investigate the effect of GR-GFP on E. coli, the growth of the host showed early rise into the exponential phase compared to the vector control strain and glucose turnover rate was elevated in increased glucose intake rate and upregulation of ATP-related genes in glycolysis (PtsG, Pgk, Pyk). Conclusion We reported the first-time potential application of GR in the form of fusion protein GR-GFP. Expression of GR-GFP in E. coli improved the production of β-carotene and RFP. Our work provides a strain of E. coli harboring phototrophic metabolism, thus paving path to a more sustainable and scalable production of biosynthesis.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Abstract 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 have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). Method This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. 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. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. Results In 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 treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91–2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77–15.71). Conclusion Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Background/Objective: 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)-induced in vitro OA model and anterior cruciate ligament transection (ACLT)-induced in vivo OA model of rabbit articular cartilage. Methods: The 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 chondrocytes in vitro, IL-1β was used to induce chondrocyte damage. Inflammatory macrophages were activated from THP-1 monocytes to observe the impact of iPSC-EV on macrophage polarisation. The phenotypes of the macrophages exposed to iPSC-EVs were evaluated by ELISA and western blot analyses. The primary chondrocytes were co-cultured with different phenotypes of macrophages to observe the expression of collagen II and catabolic enzymes in chondrocytes. iPSC-EVs were injected intraarticularly into the rabbit with an ACLT-induced OA model. The progression of lesions was assessed through macroscopic and histopathological studies. Results: We 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. Conclusion: 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. The translational potential of this article: This study highlights the potential of iPSC-EVs as a therapeutic option for chondrocyte regeneration and OA treatment.

Due to climate change, Spodoptera litura has the potential to become an increasingly severe pest because of increased habitat suitability. To support precision agriculture, it is essential to accurately predict the life cycle of Spodoptera litura, and use the information for pest control. This paper proposes BugTalk to predict the life of Spodoptera litura (Common Cutworm). Based on the Internet of Things (IoT) technology, BugTalk is a real-time prediction version of modified Insect Life Cycle Modeling software (ILCYM), an open-source software package that implements the functions used in the four models of the four life stages of Spodoptera litura. In this paper, we significantly improve the ILCYM functions and several models of the previous studies to improve the accuracy of the prediction. We develop the first real-time prediction system that can predict the number of Spodoptera litura for the farm fields in real-time. The results are compared with the measurements during 2014-2020. We extend the temperature-based ILCYM model to accommodate humidity for the larvae emergence stage, which further improves the accuracy of the model. The Mean Arctangent Absolute Percentage Error (MAAPE) between the measurements and the BugTalk prediction is 24.593%. This result has been practically utilized in farm management.

Abstract 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

Chenopodium formosanum Koidz (CF) is an indigenous cereal plant of Taiwan. Its high content of secondary metabolites and nutrients has attracted attention for its use in skin care products and functional foods. However, most studies have focused on the extract of CF seeds, which are relatively expensive, and none have investigated the effects of combining extraction and fermentation. In this study, we evaluated the utility of using extracts of different parts of CF, i.e., the leaves, stems, and unhulled and hulled seeds. We first made aqueous, ethanolic, methanolic, and ethyl acetate extracts of the four parts. After assessing their biological activities, we selected only unfermented and fermented CF leaf methanolic extracts for subsequent analysis. None of the concentrations of fermented CF leaf extract (≤400 mg/L) were cytotoxic, and all exhibited antioxidative, anti-inflammatory, antimicrobial, skin-whitening, moisturizing, and antiaging activities. The concentrations of protocatechuic acid, epicatechin, gallic acid, and quercetin increased the most after fermentation. Therefore, they were subjected to a molecular docking analysis, which revealed that quercetin and epicatechin may contribute the most to skin-whitening and antiaging properties, respectively. In conclusion, fermented CF leaf methanolic extracts can be useful as a functional ingredient in health foods, botanical drugs, and cosmetic products.

Abstract 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 (

The stability of milk-based formulas (infant formula and follow-up formula) were evaluated at 42°C and 50°C, during 90 days. Unsaturated fatty acids, color, peroxide values, headspace oxygen and volatile organic compounds (VOCs) were analyzed to evaluate the stability of milk-based formulas. No significant changes were observed in the unsaturated fatty acids (except DHA with a significant decrease after 90 days storage) of milk-based formulas stored at 42 or 50°C for 90 days. There is a significant change in color of the formulas during storage. For peroxide values and headspace oxygen, samples which were stored at a higher temperature would have higher peroxide values and less headspace oxygen after 90 days. For VOCs, results showed the significant differences of VOCs profiles in the formulas stored at different temperatures and lengths of storage period. In this study, the higher fat, the less oxidation stability was found.

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

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.

Background: Postdischarge diseases (PDDs) have been reported for adult survivors of out-of-hospital cardiac arrest (OHCA). However, the detailed demographics of pediatric OHCA survivors with PDDs are not well-documented, and information regarding functional survivors is particularly limited. We aimed to report detailed information on the PDDs of survivors of traumatic and non-traumatic pediatric OHCA using a national healthcare database.Methods: We retrospectively obtained data from the Taiwan government healthcare database (2011–2015). Information on the demographics of traumatic and non-traumatic pediatric OHCA survivors (

Cardiac troponin I (cTnI) plays an important role in the assessment of various cardiac diseases. However, accurate detection of cTnI at the point-of-care (POC) remains unfeasible. In this study, we report the development of an electrochemical immunosensor designed for rapid and accurate cTnI detection in pre-hospital settings. Rapid cTnI analysis of whole blood samples was then performed. cTnI measurements were highly correlated with the results of the standard clinical laboratory method for cTnI detection. The results of this study suggest that the proposed POC immunosensor can deliver fast and accurate cTnI analysis in pre-hospital settings to achieve rapid diagnosis and guide patient management.

Acute Coronary Syndrome (ACS) and other heart emergency events require immediate chest pain identification in the ambulance. Specifically, early identification and triage is required so that patients with chest pain can be quickly sent to a hospital with appropriate care facilities for treatment. In the traditional approach, ambulance personnel often use symptom checklists to examine the patient and make a quick decision for the target hospital. However, not every hospital has specialist facilities to handle such emergency cases. If the result of the subsequent cardiac enzyme test performed at the target hospital strongly suggests the occurrence of myocardial infarction, the patient may need to be sent to another hospital with specialist facilities, such as Percutaneous Coronary Intervention. The standard procedure is time consuming, which may result in delayed treatment and reduce patent survival rate. To resolve this issue, we propose AMBtalk (Ambulance Talk) for accurate, early ACS identification in an ambulance. AMBtalk provides real-time connection to hospital resources, which reduces the elapsed time for treatment, and therefore, improves the patient survival rate. The key to success for AMBtalk is the development of the AllCheck® Internet of Things (IoT) device, which can accurately and quickly provide cardiovascular parameter values for early ACS identification. The interactions between the AllCheck® IoT device, the emergency medical service center, the ambulance personnel and the hospital are achieved through the AMBtalk IoT server in the cloud network. AllCheck® outperforms the existing cardiovascular IoT device solutions for ambulance applications. The testing results of the AllCheck® device show 99% correlation with the results of the hospital reports. Due to its excellent performance in quick ACS identification, the AllCheck® device was awarded the 17th Taiwan Innovators Award in 2020.

Background: In children with non-shockable out-of-hospital cardiac arrest, early epinephrine (EE) might help to establish the return of spontaneous circulation (ROSC) and be associated with survival. In the present study, we aimed to analyze the effects of EE on outcomes and post-resuscitation hemodynamics in children with non-shockable OHCA.Methods: This was a retrospective analysis of data from 216 children (30 min.Results: Twenty-eight (13.0%) children survived to discharge, but only 17 (7.9%) had good neurological outcomes. In all, 41 (18.9%) children received EE; in comparison to IE and LE, this was significantly associated with tachycardia (73.9%) in the post-resuscitation period (p < 0.05). Tachycardia (OR: 7.41, 95% CI: 1.96–29.31) and hypertension (OR: 6.03, 95% CI: 1.85–13.77) were significantly associated with EE after adjusting for confounding factors. EE was also significantly associated with better overall outcomes than ME and LE (any ROSC, sustained ROSC, survival to the intensive care unit, admission, survival to discharge and good neurological outcomes, all p < 0.05).Conclusions: EE helped to establish ROSC but was also associated with more tachycardia and hypertension in the early post-resuscitation period. In children with non-traumatic and non-shockable OHCA, EE was associated with a higher survival rate and better neurological outcomes than were ME and LE.

Objective. To evaluate the efficacy of high-flow nasal cannula (HFNC) therapy compared with conventional oxygen therapy (COT) or noninvasive ventilation (NIV) for the treatment of acute respiratory failure (ARF) in emergency departments (EDs). Method. We comprehensively searched 3 databases (PubMed, EMBASE, and the Cochrane Library) for articles published from database inception to 12 July 2019. This study included only randomized controlled trials (RCTs) that were conducted in EDs and compared HFNC therapy with COT or NIV. The primary outcome was the intubation rate. The secondary outcomes were the mortality rate, intensive care unit (ICU) admission rate, ED discharge rate, need for escalation, length of ED stay, length of hospital stay, and patient dyspnea and comfort scores. Result. Five RCTs (n = 775) were included. There was a decreasing trend regarding the application of HFNC therapy and the intubation rate, but the difference was not statistically significant (RR, 0.53; 95% CI, 0.26–1.09; p=0.08; I2 = 0%). We found that compared with patients who underwent COT, those who underwent HFNC therapy had a reduced need for escalation (RR, 0.41; 95% CI, 0.22–0.78; p=0.006; I2 = 0%), reduced dyspnea scores (MD −0.82, 95% CI −1.45 to −0.18), and improved comfort (SMD −0.76 SD, 95% CI −1.01 to −0.51). Compared with the COT group, the HFNC therapy group had a similar mortality rate (RR, 1.25; 95% CI, 0.79–1.99; p=0.34; I2 = 0%), ICU admission rate (RR, 1.11; 95% CI, 0.58–2.12; p=0.76; I2 = 0%), ED discharge rate (RR, 1.04; 95% CI, 0.63–1.72; p=0.87; I2 = 0%), length of ED stay (MD 1.66, 95% CI −0.95 to 4.27), and hospital stay (MD 0.9, 95% CI −2.06 to 3.87). Conclusion. Administering HFNC therapy in ARF patients in EDs might decrease the intubation rate compared with COT. In addition, it can decrease the need for escalation, decrease the patient’s dyspnea level, and increase the patient’s comfort level compared with COT.

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.

Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma.

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.

Femoral neck fracture is common in the elderly, and its impact has increased in aging societies. Comorbidities, poor levels of activity and pain may contribute to the development of depression, but these factors have not been well addressed. This study aims to investigate the frequency and risk of major depression after a femoral neck fracture using a nationwide population-based study. The Taiwan Longitudinal Health Insurance Database was used in this study. A total of 4,547 patients who were hospitalized for femoral neck fracture within 2003 to 2007 were recruited as a study group; 13,641 matched non-fracture participants were enrolled as a comparison group. Each patient was prospectively followed for 3 years to monitor the occurrence of major depression. Cox proportional-hazards models were used to compute the risk of major depression between members of the study and comparison group after adjusting for residence and socio-demographic characteristics. The most common physical comorbidities that were present after the fracture were also analyzed. The incidences of major depression were 1.2% (n = 55) and 0.7% (n = 95) in the study and comparison groups, respectively. The stratified Cox proportional analysis showed a covariate-adjusted hazard ratio of major depression among patients with femoral neck fracture that was 1.82 times greater (95% CI, 1.30-2.53) than that of the comparison group. Most major depressive episodes (34.5%) presented within the first 200 days following the fracture. In conclusion, patients with a femoral neck fracture are at an increased risk of subsequent major depression. Most importantly, major depressive episodes mainly occurred within the first 200 days following the fracture.

OBJECTIVE: To analyze whether urine output and urinalysis results are predictive of survival and neurologic outcomes in patients with non-traumatic out-of-hospital cardiac arrest (OHCA). METHODS: Information was obtained from 1,340 patients with non-traumatic OHCA who had achieved a sustained return of spontaneous circulation (ROSC). Factors that were associated with survival in the post-resuscitative period were evaluated. The association between urine output and fluid challenge in the early resuscitative period was analyzed and compared between the survivors and the non-survivors. The results of the initial urinalysis, including the presence of proteinuria and other findings, were used to evaluate the severity of vascular protein leakage and survival. The association between proteinuria and the neurologic outcomes of the survivors was also analyzed. The clinical features of capillary leakage were examined during the post-resuscitative period. RESULTS: Of the 1,340 patients, 312 survived. A greater urine output was associated with a higher chance of survival. The initial urine output increased in proportion to the amount of fluid that was administered during early resuscitation in the emergency department for the survivors but not for the non-survivors (p

Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H(2)O(2)-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL-induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.