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Increasing world population has markedly increased the demand for vegetable oils for domestic and industrial purposes. Plant-based vegetable oils have been identified as one of the oils with high nutritive value. Castor plant is one of the oilseed with rich oil content owing to its high monounsaturated fatty acid and bioactive compounds. Its fatty acid profile constitutes mainly of ricinoleic acid and other minor acids such as stearic, palmitic, and oleic acid. Ricinoleic acid of castor oil is unique among all other vegetable oils, making it attractive for a wide spectrum of applications. The predominant triglyceride component in the oil is triricinolein. Minor biological compounds including carotenoid, tocopherol, tocotrienol, phytosterol, phospholipid, phytochemical, and phenolic compounds are present in castor oil. These compounds offer oxidation stability, anti-inflammatory, and antioxidant properties to the oil. The acid, anisidine, iodine, viscosity, and saponification values indicate that castor has good oil quality compared to other vegetable oils. Castor oil composition is influenced by the area of production and method of extraction adopted. The chemical structure of castor oil is centered on the ricinoleic acid and three major functional groups linked by glycerol moiety. More research on the oil’s component is being investigated nevertheless efficient and eco-friendly extraction methods are required. This review, therefore, summarizes the castor oil composition namely the triglyceride, various fatty acids and bioactive compounds, extraction methods, as well as its physicochemical properties.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread around the world. However, approaches to distinguish COVID-19 from pneumonia caused by other pathogens have not yet been reported. We retrospectively analyzed the clinical data of 97 children with probable COVID-19. A total of 13 (13.4%) patients were confirmed positive for SARS-CoV-2 infection by nucleic acid RT-PCR testing, and 41 (42.3%) patients were found to be infected with other pathogens. Notably, no pathogen was detected in 43 (44.3%) patients. Among all patients, 25 (25.8%) had familial cluster exposure history, and 52 (53.6%) had one or more coexisting conditions. Fifteen (15.5%) patients were admitted or transferred to the PICU. In the 11 confirmed COVID-19 cases, 5 (45.5%) and 7 (63.6%) were positive for IgM and IgG against SARS-CoV-2, respectively. In 22 patients with suspected COVID-19, 1 (4.5%) was positive for IgG but negative for IgM. The most frequently detected pathogen was Mycoplasma pneumonia (29, 29.9%). One patient with confirmed COVID-19 died. Our results strongly indicated that the detection of asymptomatic COVID-19 or coexisting conditions must be strengthened in pediatric patients. These cases may be difficult to diagnose as COVID-19 unless etiologic analysis is conducted. A serologic test can be a useful adjunctive diagnostic tool in cases where SARS-CoV-2 infection is highly suspected but the nucleic acid test is negative. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11684-020-0820-7 and is accessible for authorized users.

Right ventricular (RV) dysfunction can occur after cardiac surgery and persist for years. We assessed perioperative RV systolic function in patients undergoing mitral valve (MV) repair and further compared minimally invasive robotic-assisted mitral valve repair (MIMVr) vs standard 'open' MV repair (MVr). Speckle tracking (RV free wall strain [RVS]) was used as a sensitive echocardiography method to assess RV function.Retrospective analysis, over 3 years, of consecutive patients (n = 158) referred to Mayo Clinic (Rochester, MN, USA). Preoperative, pre-discharge and 1 year transthoracic echocardiograms were reviewed. A prospective pilot study was performed for sample size estimation. Primary outcome was RV free wall strain (RVS).Right ventricular free wall strain declined after MV repair surgery (-22.6 ± 7% vs -15 ± 6%, p 0.001). There were smaller reductions in RVS in MIMVr vs MVr group (-6.0 ± 9% vs -10.3 ± 8%, p 0.01), which persisted after adjusting for baseline values (RVS treatment effect 1.5%, p = 0.007). There was greater recovery in MIMVr vs MVr group at 1 year follow-up vs pre-surgery values (-3.4 ± 9% vs -8.1 ± 8% respectively, p 0.001, RVS treatment effect 1.7%, p = 0.001). Bypass time was higher in the MIMVr group (80min ± 22 vs 40min ± 20, p 0.0001). The echo findings remained significant correcting for age, pulmonary pressures and change in ejection fraction.Right ventricular systolic dysfunction is common after MV repair surgery. Deterioration in RV contraction is less pronounced following MIMVr vs MVr and is associated with enhanced RV functional recovery at 1 year, albeit not to preoperative levels. This may potentially be associated with clinical functional improvement but further studies are warranted to investigate this.

Fusidane-type antibiotics are a group of triterpenoid antibiotics. They include helvolic acid, fusidic acid, and cephalosporin P1, among which fusidic acid has been used clinically. We have recentl...

Background The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. Methods HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. Results HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p Conclusion HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.

Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation.We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center.There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications.m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio lOR], 3.57; P Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width

Background Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. Methods INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January–June 2019, period 1) and a portion of the COVID-19 pandemic period (January–June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. Results Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. Conclusion The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.

Aims SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and results Adenovirus expressing Ubc9 was administrated by multipoint injection in the border zone of heart immediately after MI in C57BL/6 mice. Neonatal rat cardiomyocytes (NRCMs) were also infected, followed by oxygen and glucose deprivation (OGD). In vivo, Ubc9 adenovirus-injected mice showed decreased cardiomyocyte apoptosis, reduced myocardial fibrosis, and improved cardiac function post-MI. In vitro, overexpression of Ubc9 decreased cardiomyocyte apoptosis, whereas silence of Ubc9 showed the opposite results during OGD. We next found that Ubc9 significantly decreased the accumulation of autophagy marker p62/SQSTM, while the LC3 II level hardly changed. When in the presence of bafilomycin A1 (BAF), the Ubc9 adenovirus plus OGD group presented a higher level of LC3 II and GFP-LC3 puncta than the OGD group. Moreover, the Ubc9 adenovirus group displayed increased numbers of yellow plus red puncta and a rising ratio of red to yellow puncta on the mRFP-GFP-LC3 fluorescence assay, indicating that Ubc9 induces an acceleration of autophagic flux from activation to degradation. Mechanistically, Ubc9 upregulated SUMOylation of the core proteins Vps34 and Beclin1 in the class III phosphatidylinositol 3-kinase (PI3K-III) complexes and boosted the protein assembly of PI3K-III complex I and II under OGD. Moreover, the colocalization of Vps34 with autophagosome marker LC3 or lysosome marker Lamp1 was augmented after Ubc9 overexpression, indicating a positive effect of Ubc9-boosted protein assembly of the PI3K-III complexes on autophagic flux enhancement. Conclusions We uncovered a novel role of Ubc9 in protecting cardiomyocytes from ischemic stress via Ubc9-induced SUMOylation, leading to increased PI3K-III complex assembly and autophagy-positioning. These findings may indicate a potential therapeutic target, Ubc9, for treatment of myocardial ischemia.

The paradigm of positive psychology, significant in nature, helps to explain the proactivity and motivation of human agency, such as a secondary school student’s state of autonomy, confidence, and personal resolve to strive for optimal learning and/or non-learning experiences. Our recent research development, in tandem with other scholars’ inquiries, has focused on one aspect of positive psychology–namely, a person’s achievement of ‘optimal best’, which reflects the maximization of his/her state of functioning (e.g., cognitive functioning). Capitalizing on our previous research, we develop a psychological concept that we term as a ‘perceived feeling of energy’. A perceived feeling of energy (e.g., a perceived feeling of liveliness) is proposed to act as a ‘motivational engine’, or as a central driver, which then could predict and enhance a person’s achievement of optimal best. Six hundred and twenty-seven university students (N = 438 women, 189 men) responded to a suite of self-report questionnaires. Structural equation modelling (SEM) techniques were used to test a conceptual model, where we focused on the antecedent (i.e., the direct impact of self-efficacy on a perceived feeling of energy) and consequence of a perceived feeling energy (i.e., the impact of a perceived feeling of energy on personal resolve, and the sustaining of optimal best). Analysis of results showed support for our original hypothesized model–for example: self-efficacy as an antecedent of energy and the central role of the energy as a predictor and potential mediator of future outcomes.

With over 20 years of the opioid crisis, our collective response has evolved to address the ongoing needs related to the management of opioid use and opioid use disorder. There has been an increasing recognition of the need for standardized metrics to evaluate organizational management and stewardship. The clinical laboratory, with a wealth of objective and quantitative health information, is uniquely poised to support opioid stewardship and drive valuable metrics for opioid prescribing practices and opioid use disorder (OUD) management. To identify laboratory-related insights that support these patient populations, a collection of 5 independent institutions, under the umbrella of the Clinical Laboratory 2.0 movement, developed and prioritized metrics. Using a structured expert panel review, laboratory experts from 5 institutions assessed possible metrics as to their relative importance, usability, feasibility, and scientific acceptability based on the National Quality Forum criteria. A total of 37 metrics spanning the topics of pain and substance use disorder (SUD) management were developed with consideration of how laboratory insights can impact clinical care. Monitoring these metrics, in the form of summative reports, dashboards, or embedded in laboratory reports themselves may support the clinical care teams and health systems in addressing the opioid crisis. The clinical insights and standardized metrics derived from the clinical laboratory during the opioid crisis exemplifies the value proposition of clinical laboratories shifting into a more active role in the healthcare system. This increased participation by the clinical laboratories may improve patient safety and reduce healthcare costs related to OUD and pain management.

Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown mechanisms of pathogenicity or risk factors. We aimed to verify whether human leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han Chinese population. We carried out an association study including 12 subjects with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of 12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received XST via intravenous drip. The carrier frequency of HLA-C*12:02 was significantly high compare to that of the control population (Pc = 4.4 × 10−4, odds ratio (OR) = 21.75, 95% CI = 5.78–81.88). Compared with that of the XST-tolerant group, the patients who received XST through intravenous drip presented a higher OR of cADRs (Pc = 0.011, OR = 27.00, 95% CI = 2.58–282.98). The results suggest that HLA-C*12:02 is a potentially predictive marker of XST-induced cADRs in Han Chinese, especially when XST is administered via intravenous drip.

Objectives A meta-analysis was performed to observe whether a difference in miRNA-221/222 expression exists in thyroid cancer with normal thyroid or BTLs (benign thyroid lesions) and, under this premise, assess its diagnostic efficacy for thyroid cancer. Methods Systematic electronic literature searches were conducted to include PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science. The combined fold change (FC) was calculated, and pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves were calculated. Results Twenty-seven articles were included in this meta-analysis. The combined FC of miRNA-221/222 were 13.85 and 13.75 in thyroid cancer with normal control. For miRNA-221/222, the pooled sensitivity was 0.79 (95% CI = 0.73–0.85), specificity was 0.84 (95% CI = 0.76–0.90) and AUC (area under the curve) value was 0.88 (0.85–0.91). For miRNA-221, the pooled sensitivity was 0.82 (95% CI = 0.76–0.86) and specificity was 0.84 (95%CI = 0.74–0.91). For miRNA-222, the pooled sensitivity was 0.78 (95%CI = 0.68–0.85) and specificity was 0.83 (95% CI = 0.70–0.92). Conclusion Differences in expression levels of miRNA-221/222 can provide clues for exploring the etiology of thyroid cancer. In addition, miRNA-221/222 were promising molecular biomarkers that may significantly improve the diagnostic accuracy of thyroid cancer.

Abeo-nodulisporisteroid A (1), an abnormal steroid with a rearranged C3 chain at C-9 possibly derived from seco-ring A via Wagner-Meerwein rearrangement and oxidations, was obtained from Nodulisporium sp. together with five related new seco-progesteroids (nodulisporisteroids M-Q, 2–6), which were elucidated by the extensive spectroscopic analysis and X-ray crystallography. A plausible biosynthetic pathway of 1–6 was also proposed. Furthermore, these isolated compounds were also evaluated for cytotoxicities against five human tumour cell lines, antimicrobial activities, and inhibitions against PI3K gamma, Aβ42 aggregation, and α-glucosidase.

Malectin is a newly discovered endoplasmic reticulum (ER)-resident lectin, which specifically recognizes Glc2Man9GlcNAc2 on newly synthesized glycoproteins. We have previously demonstrated that malectin forms a complex with ribophorin I for selective retention of misfolded glycoproteins inside the cell. Here, we showed that ribophorin I also functions to regulate the subcellular localization of malectin under various conditions. Even though malectin does not contain an ER-retention signal motif, we found that endogenous malectin mainly localizes in the ER, which is disrupted upon suppression of ribophorin I, leading to its movement from ER to Golgi. In contrast, under ER-stress conditions, malectin mainly localizes in the Golgi, which is restored to ER localization by overexpression of ribophorin I. These results indicate that the subcellular localization of malectin is accurately regulated by the expression level of ribophorin I, which will provide further insights into the understanding of the function of malectin.

A new cell line was isolated and characterized from the head kidney of Siganus fuscescens (rabbit fish). The new macrophagic-like cell line was named as r abbit f ish m acrophage (RFM), and which could be sub-cultured for over 50 cycles since the development. RFM cell line was tested for growth in different temperatures and serum concentrations: the best growing condition was optimized at 20% serum under 28 °C. In cultured RFM cells, sequencing of 18S rRNA, as well as immunostaining of cytokeratin and CD 68, confirmed the identity as macrophagic cell of S. fuscescens. Cultured RFM cells were exposed to challenge of inflammation, as triggered by LPS, showing highly sensitive responses to inflammation, including release of nitric oxide, expression of cytokine, and activation of phagocytosis. The water extract of aerial part of Scutellaria baicalensis, named as SBA, has been shown anti-inflammatory property in S. fuscescens fish. In order to extend the application of SBA in aquaculture, the extract and its effective flavonoids, i.e. baicalin and scutellarin, were applied in LPS-treated RFM cells. Application of SBA extract, baicalin or scutellarin, inhibited the expressions of LPS-induced inflammatory cytokines, i.e. IL-1β, TNF-α, as well as the signaling of transcription factor NF-κB. The results support the established RFM cell line could be an ideal in vitro model in drug screening relating to inflammation. Additionally, the notion of SBA herbal extract in fish aquaculture is supported by its efficacy against inflammation.

Phyllomeroterpenoids A−C (1−3), multi-biosynthetic pathway derived meroterpenoids from amino acid/pentose phosphate/terpenoid pathways, were isolated from the TCM endophytic fungus Phyllosticta sp. J13-2-12Y, together with six biosynthetically related compounds (4−9). All structures were determined by extensive spectroscopic analysis, chemical derivatization, and ECD experiments. A plausible biosynthetic pathway of 1−3 was proposed. In addition, the antimicrobial activities of all isolated compounds were evaluated against Staphylococcus aureus 209P (bacterium) and Candida albicans FIM709 (fungus).

// Chih-Hung Chen 1 , Yung-Lung Chen 2 , Pei-Hsun Sung 2 , Cheuk-Kwan Sun 3 , Kuan-Hung Chen 4 , Yi-Ling Chen 2 , Tien-Hung Huang 2 , Hung-I Lu 5 , Fan-Yen Lee 5 , Jiunn-Jye Sheu 5 , Sheng-Ying Chung 2 , Mel S. Lee 6, * and Hon-Kan Yip 2, 7, 8, 9, 10, * 1 Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan 4 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 7 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 8 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 9 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 10 Department of Nursing, Asia University, Taichung, Taiwan * Both authors contributed equally to this work Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Mel S. Lee, email: mellee@cgmh.org.tw Keywords: acute respiratory distress syndrome, sepsis, inflammation, adipose-derived mesenchymal stem cell, platelets Received: October 11, 2016 Accepted: March 06, 2017 Published: July 17, 2017 ABSTRACT This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1.2x10 6 cells), ARDS-LPS-PreD-SCP (3.0x10 8 , intravenous administration), and ARDS-LPS-ADMS/PreD-SCP groups, and were sacrificed 72 h after 48 h ARDS induction. Lung injury scores (LIS) and collagen deposition were highest in ARDS-LPS, lowest in SC, higher in ARDS-LPS+ADMSC than in ARDS-LPS+PreD-SCP and ARDS-LPS+ADMS/PreD-SCP, and higher in ARDS-LPS+PreD-SCP than in ARDS-LPS+ADMS/PreD-SCP (all p

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p

// Fan-Yen Lee 1, * , Kuan-Hung Chen 2, * , Christopher Glenn Wallace 3 , Pei-Hsun Sung 4 , Jiunn-Jye Sheu 1 , Sheng-Ying Chung 4 , Yung-Lung Chen 4 , Hung-I Lu 1 , Sheung-Fat Ko 5 , Cheuk-Kwan Sun 6 , Hsin-Ju Chiang 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9, ** and Hon-Kan Yip 4, 10, 11, 12, 13, ** 1 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, Royal Devon & Exeter Hospital, Exeter, United Kingdom 4 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan 7 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Nursing, Asia University, Taichung, Taiwan 13 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work ** These authors have contributed equally to this work senior co-authors Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Keywords: acute respiratory distress syndrome, sepsis syndrome, inflammatory and immune reactions, xenogeneic mesenchymal stem cell, mortality Received: January 10, 2017 Accepted: April 03, 2017 Published: April 21, 2017 ABSTRACT This study tested the hypothesis that xenogeneic human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy would improve survival rates in rats with acute respiratory distress-syndrome (ARDS, induction by 48 h inhalation of 100% oxygen) and sepsis-syndrome (SS, induction by cecal-ligation and puncture) (ARDS-SS). Adult-male Sprague-Dawley rats were categorized into group 1 (sham-controls), group 2 (ARDS-SS), group 3 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 1 h after SS-induction)], and group 4 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 24 h after SS-induction)]. The mortality rate was higher in groups 2 and 4 than in groups 1 and 3 (all p

This study tested the therapeutic impact of double-loading dose (i.e., 600 mg) versus standard-loading dose (i.e., 300 mg) of clopidogrel on ST-segment-elevation-myocardial-infarction (STEMI) patients undergoing primary-coronary-intervention (PCI).Between January 2005 and December 2013, a total of 1461 STEMI patients undergoing PCI were consecutively enrolled into the study and categorized into group 1 (600 mg/clopidogrel; n = 508) and group 2 (300 mg/clopidogrel; n = 953). We assessed angiographic thrombolysis-in-myocardial-infarction (TIMI) flow in the infarct-related-artery, 30-day mortality and upper-gastrointestinal-bleeding (UGIB) within 30 days as primary-endpoints and later incidents of UGIB as secondary-endpoints.The results showed that the incidences of advanced Killip score (defined as ≥ score 3) upon presentation (23.8% versus 24.6%) and advanced heart failure (defined as ≥ NYHAFc-3) (10.2% versus 10.4%) did not differ between groups 1 and 2 (all P > 0.4). Primary-endpoints, which were final TIM-3 flow (91.3% versus 91.7%) in the infarct-related-artery, incidences of 30-day mortality (5.8% vs. 7.1%), and UGIB ≤ 30 day (7.8% versus 8.9%) did not differ between group 1 and group 2 (all P > 0.33). The secondary-endpoints which were incidences of ≥ 30-day one-year (8.9% versus 10.1%) UGIB did not differ between groups 1 and 2 (all P > 0.45). One-year mortality did not differ between two groups (10.74% versus 12.9%) (P > 0.25). Multiple-stepwise-logistic-regression analysis showed that age and advanced-Killip score were independently predictive of 30-day mortality (all P < 0.001).Double-loading dose of clopidogrel did not confer an additional benefit to the final angiograph results, 30-day/one-year clinical outcomes; and age and advanced Killip-score were powerful predictors of 30-day mortality.

Aim In the present study, we purposed to determine serum chitinase 3‐like 1 (CHI3L1) expression characteristics in chronic liver diseases monoinfected with hepatitis B virus and analyze its diagnostic value in liver fibrosis. Methods A total of 467 chronic hepatitis B (CHB) patients, 312 liver cirrhosis (LC) patients, and 104 hepatocellular carcinoma (HCC) patients at our institution were enrolled, and clinical indicators were analyzed. Results Our data have shown that the expression level of serum CHI3L1 was steadily increased from CHB to LC to HCC (P

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.

Damaged endothelial progenitor cells (EPCs) are associated with poor prognosis in diabetic myocardial infarction (DMI). Our previous studies revealed that an impaired Sonic hedgehog (Shh) pathway contributes to insufficient function in diabetic EPCs; however, the roles of the Shh pathway in diabetic EPC apoptosis under basal and hypoxic/ischemic conditions remain unknown. Therefore, the present study investigated whether Shh revitalized diabetic EPCs and consequently improved the deteriorative status of DMI. For this purpose, streptozotocin injection was used in male C57/BL6 mice to induce type‑1 diabetes, and diabetic EPCs were isolated from the bone marrow. Apoptosis, cell function, and protein expression were investigated in EPCs in vitro. Mouse hearts were injected with adenovirus Shh‑modified diabetic EPCs (DM‑EPCShh) or control DM‑EPCNull immediately after coronary artery ligation in vivo. Cardiac function, capillary numbers, fibrosis, and cell apoptosis were then detected. First, the in vitro results demonstrated that the apoptosis of diabetic EPCs was reduced following treatment with Shh protein for 24 h, under normal or hypoxic conditions. BMI1 proto‑oncogene (Bmi1), an antiapoptotic protein found in several cells, was reduced in diabetic EPCs under normal or hypoxic conditions, but was upregulated after Shh protein stimulation. When Bmi1‑siRNA was administered, the antiapoptotic effect of Shh protein was significantly reversed. In addition, p53, a Bmi1‑targeted gene, was demonstrated to mediate the antiapoptotic effect of the Shh/Bmi1 pathway in diabetic EPCs. The Shh/Bmi1/p53 axis also enhanced the diabetic EPC function. In vivo, Shh‑modified diabetic EPCs exhibited increased EPC retention and decreased apoptosis at 3 days post‑DMI. At 14 days post‑DMI, these cells presented enhanced capillary density, reduced myocardial fibrosis and improved cardiac function. In conclusion, the present results demonstrated that the Shh pathway restored diabetic EPCs through the Shh/Bmi1/p53 axis, suppressed myocardial apoptosis and improved myocardial angiogenesis, thus reducing cardiac fibrosis and finally restoring myocardial repair and cardiac function in DMI. Thus, the Shh pathway may serve as a potential target for autologous cell therapy in diabetic myocardial ischemia.

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17&ndash, 25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p &lt, 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p &lt, 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p &lt, 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

The current study aimed to evaluate the expression and role of miR‐323a in the progression of bladder cancer (BC), thereby providing a theoretical basis and potential therapy methods for BC patients. Our data showed that miR‐323a levels were significantly reduced in BC tissues compared with those of non‐cancerous tissues. Meanwhile, miR‐323a was significantly decreased in human BC cell lines (T24, J82, TCCSUP, RT‐112) than that in human normal bladder epithelial cell line SV‐HUC‐1. Furthermore, inhibition of miR‐323a markedly enhanced the migration and invasive capacity of T24 and TCCSUP cells. Moreover, overexpression of miR‐323a significantly prompted the apoptosis of BC cells. Dual luciferase reporter assay and western blot analysis confirmed that c‐Met was a target gene of miR‐323a. More importantly, upregulation of c‐Met significantly prompted BC cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c‐Met was silenced in BC cells. In summary, reduced miR‐323a expression in BC contributed to enhanced BC cell proliferation and migration mainly by targeting c‐Met.

The study of optimal best practice within the context of academia has produced both empirical and theoretical contributions. Optimal best practice, also coined as optimal functioning, is concerned with a person's personal best-that is, "what is the best that I can do for this academic subject?" Research in the social sciences has, to date, explored different types of optimal best-physical, cognitive, emotional, and social. What is of considerable interest, as a related matter, is a question of how a person reaches and experiences a level of optimal best practice. Recent research development, for example, has explored various conceptualizations of optimal best practice-for example, one distinctive theoretical model, the Framework of Achievement Bests [1, 2], makes a concerted effort to explore the underlying process of optimization-that is, in this case, how an optimal level of best practice is achieved. The present study, as detailed below, investigates via means of non-experimental data a theoretical model pertaining to the achievement of optimal best practice. This examination, we postulate, would enable us to add clarity and provide additional theoretical insights the operational nature of the process of optimization. The operational nature of optimization, as described in our recent research [1, 3], emphasizes three major tenets: (i) the main sources of a person's optimal best practice, (ii) the potential 'optimizing' influences of three comparable agencies on the achievement of optimal best practice (i.e., personal resolve, social relationship, and personal self-efficacy), and (iii) the impact of optimal best practice on future adaptive outcomes (i.e., academic striving and personal well-being). We explored this topic via means of the use of a non-experimental, correlational design with participants drawn from Taiwanese university students (N = 1010). Structural equation modelling (SEM) produced evidence, which empirically supported existing research [1, 3] and substantiated our knowledge of the concept of optimal best practice. Evidence established from the present study has also assisted us to identify one pervasive issue, which we call for further research development-namely, to consider, design, and develop an appropriate methodological approach that would enable researchers to accurately measure and assess the process of optimization. Finally, in terms of teaching and learning, we acknowledge that our research investigation has provided some insights into potential educational practices for implementation.

Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. Results: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors&mdash, vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1&alpha, /HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p &lt, 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p &lt, 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p &lt, 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area.

Genetic analysis of 111 patients with phenylketonuria or hyperphenylalaninemia has uncovered a novel 8 bp deletion variant in the phenylalanine hydroxylase gene. The novel deletion mutation c.1034_1041del generated a protein-coding frameshift and resulted in a premature stop codon rendering severe disruption of enzymatic activity. Molecular and clinical evidence also implies that the missense mutation c.301G>A is likely to be mildly pathogenic, although it was previously reported as a benign variant.

This study investigated the 30-day and long-term prognostic outcomes in patients with ST-segment elevation myocardial infarction (STEMI) complicated with profound cardiogenic shock (CS) undergoing early routine extracorporeal membrane oxygenator (ECMO)-assisted primary percutaneous coronary intervention (PCI).Between December 2005 and December 2014, 65 consecutive STEMI patients with profound CS underwent routine ECMO-supported primary PCI.The incidences of acute pulmonary edema, respiratory failure with requirement of mechanical ventilatory support upon presentation, and 30-day mortality rate were 100%, 95.4%, and 43.1%, respectively. The duration of hospitalization, mean long-term follow-up, and survival rate were 32.1±53.1 (days), 733.6±986.7 (days), and 32.3%, respectively. The mean APACHE score (32.6±8.3 vs. 28.5±7.5), peak serum creatinine level (4.3±2.4 vs. 1.7±1.2mg/dL), incidences of failed ECMO weaning (57.1% vs. 0%), successful ECMO weaning but in-hospital death (40.0% vs. 0%) were significantly lower in 30-day survivors than those in non-survivors (all p0.05), whereas final thrombolysis in myocardial infarction (TIMI)-3 flow [53.6% vs. 91.9%] showed an opposite pattern compared to that of APACHE score in the two groups (p0.02). Multivariate analysis demonstrated that unsuccessful reperfusion, failed ECMO weaning, and peak creatinine level were independent predictors of 30-day mortality (all p0.01).Early ECMO-supported primary PCI in STEMI patients with profound CS was feasible as a life-saving strategy with acceptable 30-day and long-term prognostic outcomes.

Factors leading to the formation of a hexahydroaporphine-like cyclizing side product were studied systematically for the first time and the ratio of this side product was controlled effectively. To understand better the electronic effect of substrates on the formation of side products, different 1-benzyloctahydroisoquinolines with substituted groups on nitrogen or benzene ring were compared. A plausible mechanism of cyclizing reaction was proposed, and key intermediates as well as transition states were analyzed using DFT calculations.

Objectives Analysis of serum/plasma methylmalonic acid (MMA) is important for the diagnosis and management of methylmalonic acidemia in pediatric populations. This work focuses on developing and validating a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to monitor methylmalonic acidemia using a simple method preparation. Design and methods MMA and stable isotope labeled d 3 -MMA was extracted using supported liquid extraction (SLE). Assay imprecision, bias, linearity, recovery and carryover were determined. The relationship between MMA and propionyl acylcarnitine (C3-acylcarnitine) was also evaluated using historical paired results from 51 unique individuals. Results Baseline separation between MMA and succinic acid was completed in 7 min. The assay was linear from 0.1 to 500 μM. The intra-day and inter-day imprecision CV ranged from 4.1 to 13.2% (0.3 to 526 μM) and 5.0 to 15.7% (0.3 to 233 μM), respectively. Recovery ranged from 93 to 125%. The correlation with a national reference laboratory LC-MS/MS assay showed a Deming regression of 1.026 and intercept of − 1.335. Carryover was determined to be Conclusion This report describes the first LC-MS/MS method using SLE for MMA extraction. In addition, we illustrate the challenges encountered during this method development that should be assessed and resolved by any laboratory implementing a SLE LC-MS/MS assay designed to quantify analytes across several orders of magnitude.

Liver cancer is the fifth most commonly diagnosed malignancy, of which hepatocellular carcinoma (HCC) represents the dominating histological subtype. Antiangiogenic therapy aimed at vascular endothelial growth factor (VEGF) has shown promising but deficient clinical prospects on account of vasculogenic mimicry, a highly patterned vascular channel distinguished from the endothelium-dependent blood vessel, which may function as blood supply networks occurring in aggressive tumors including HCC. In this study, we used a new cationic peptide, disulfide cross-linked stearylated polyarginine peptide modified with histidine (H3R5), as a reducible vector, cell penetrating peptide-modified aptamer (ST21) with specific binding to HCC cells to conjugate to peptide H3R5 as the targeting probe, miRNA-195 (miR195) as a powerful gene drug to inhibit VEGF, and fasudil to suppress vasculogenic mimicry by blocking ROCK2, all of which were simultaneously encapsulated in the same nanoparticles. Fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient and miR195 was condensed through electrostatic interaction. ST21-H3R5-polyethylene glycol (PEG) exhibited excellent loading capacities for both fasudil and miR195 with adjustable dosing ratios. Western blot analysis showed that (Fasudil)ST21-H3R5-PEGmiR195 had strong silencing activity of ROCK2 and VEGF, as compared with (Fasudil)H3R5-PEGmiR195. In vitro and in vivo experiments confirmed that ST21-modified nanoparticles showed significantly higher cellular uptake and therapeutic efficacy in tumor cells or tumor tissues than the unmodified counterparts. These findings suggest that aptamer-conjugated peptide holds great promise for delivering chemical drugs and gene drugs simultaneously to overcome HCC.

We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 104 cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 105 intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS-ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS-ADMSC-ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor-1α, nuclear factor-κB, matrix metallopeptidase-9, regulated on activation, normal T-cell expressed and secreted, interleukin-1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP-ribose] polymerase 1, p21 protein [Cdc42/Rac]-activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)-1, NOX-2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat. Significance Autologous adipose-derived mesenchymal stem cell-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats.

Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model.Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs.TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1(+) and HIF-1α(+) cells in pulmonary artery, and number of γ-H2AX(+) and Ki-67(+) cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice.Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.

We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult male Sprague Dawley rats (n = 40) equally divided into sham-control (SC), IR (60-min left-lobe ischemia + 72-hr reperfusion), IR-Mel (melatonin at 30 min/6/8 hr after reperfusion), IR-Mito (mitochondria 15,000 μg/rat 30 min after reperfusion), and IR-Mel-Mito. Following menadione treatment in vitro, oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved caspase-3/PARP), DNA damage (γ-H2AX/CD90/XRCC1), mitochondria damage (cytosolic cytochrome c) biomarkers, and mitochondrial permeability transition were found to be lower, whereas mitochondrial cytochrome c were found to be higher in hepatocytes with melatonin treatment compared to those without (all P < 0.001). In vivo study demonstrated highest liver injury score and serum AST in IR group, but lowest in SC group and higher in IR-Mito group than that in groups IR-Mel and IR-Mel-Mito, and higher in IR-Mel group than that in IR-Mel-Mito group after 72-hr reperfusion (all P < 0.003). Protein expressions of inflammatory (TNF-α/NF-κB/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/PARP/Bax), and mitochondria damage (cytosolic cytochrome c) biomarkers displayed an identical pattern, whereas mitochondria integrity marker (mitochondrial cytochrome c) showed an opposite pattern compared to that of liver injury score (all P < 0.001) among five groups. Microscopically, expressions of apoptotic nuclei, inflammatory (MPO(+) /CD68(+) /CD14(+) cells), and DNA damage (γ-H2AX(+) cells) biomarkers exhibited an identical pattern compared to that of liver injury score (all P < 0.001) among five groups. Melatonin-supported mitochondria treatment offered an additional benefit of alleviating hepatic IR injury.

We tested the hypothesis that tissue plasminogen activator (tPA) deficiency protected against acute ischemic stroke (AIS)-induced brain injury.Wild-type mice (n=54) were categorized into group 1 (sham control, n=18) and group 3 [AIS by permanent ligation of left common carotid artery (CCA) and cramping right CCA for 1h and then reperfusion followed by hypoxia (11% of oxygen supply for 2h), n=36]. Similarly, tPA knockout (tPA(-/-)) mice (n=54) were randomized into group 2 (sham control, n=18) and group 4 (AIS, n=36). By day 28 after AIS procedure, mortality rate was higher in group 3 (77.8%) than in group 4 (38.9%) and lowest in groups 1 (0%) and 2 (0%) (p0.001). By days 3 and 28, MRI demonstrated a pattern of changes in brain-infarct volume identical to that of mortality among four groups (p0.001). By day 28, protein expressions of inflammatory (MMP-9, TNF-α, NF-κB, iNOS, PAI-1, RANTES), oxidative (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase-3PARP, Bax), and fibrotic (Smad3, TGF-β) biomarkers and cellular expressions of inflammation (CD11, F4/80, GFAP), DNA-damage (γ-H2AX) and brain-edema (AQP4) markers exhibited an identical pattern compared to that of mortality (all p0.001), whereas protein expressions of endothelial (eNOS, CD31), anti-fibrotic (Smad1/5, BMP-2) biomarkers, and number of small vessels displayed an opposite pattern (all p0.001) among four groups. Expressions of protein and cellular angiogenesis markers (VEGF, SDF-1α, CXCR4) were progressively increased from groups 1 and 2 to group 4 (all p0.0001).tPA deficiency protected the brain from AIS injury.