Anti-inflammatory in vitro activities of eleven selected caffeic acid derivatives based on a combination of pro-/anti-inflammatory cytokine secretions and principal component analysis - A comprehensive evaluation.

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1ß, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC50: >50 µmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 µmol/l and 5-CQA at 25 µmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases.

Fabrication of a decellularized liver matrix-based hepatic patch for the repair of CCl4-induced liver injury.

This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin-DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin-complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.

Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer.

Over the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10-15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25-200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment.

Applications of dynamic visual acuity test in clinical ophthalmology.

Dynamic visual acuity test (DVAT) plays a key role in the assessment of vestibular function, the visual function of athletes, as well as various ocular diseases. As the visual pathways conducting dynamic and static signals are different, DVATs may have potential advantages over the traditional visual acuity tests commonly used, such as static visual acuity, contrast sensitivity, and static perimetry. Here, we provide a review of commonly applied DVATs and their several uses in clinical ophthalmology. These data indicate that the DVAT has its unique clinical significance in the evaluation of several ocular disorders.

Selective activation of pro-anti-IL-1ß antibody enhances specificity for autoinflammatory disorder therapy.

Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1ß and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1ß by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1ß-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1ß-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1ß neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1ß-downstream signaling and IL-1ß-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.

Innovative Mind-Body Intervention Day Easy Exercise Increases Peripheral Blood CD34+ Cells in Adults.

Mind-body interventions (MBIs) have many health benefits, such as reducing stress, modulating blood pressure, and improving sleep and life quality. The long-term practice of Tai chi, an MBI, also increases the number of CD34+ cells, which are surface markers of hematopoietic stem cells, so prolonged Tai chi practice may have antiaging effects. We developed the day easy exercise (DEE), an innovative MBI, that is easy to learn and requires only a small exercise area and a short practice time. The aim of this study was to explore whether DEE, like Tai chi, has antiaging effects after short-term practice. Total 44 individuals (25 to 62 years old) with or without 3-month DEE practice were divided into young- and middle-aged groups (≤30 and >30 years old) and peripheral blood was collected at 0, 1, 2, and 3 months for analysis of CD34+ cells. The number of CD34+ cells in peripheral blood remained unchanged in control young- and middle-aged groups. After DEE, the number of CD34+ cells in peripheral blood was increased over time in both young- and middle-aged groups. For young-aged adults, the cell number was markedly increased by threefold at 3 months after DEE, and for middle-aged adults, the increase was significant from the first month. DEE practice indeed increased the number of CD34+ cells in peripheral blood and the increase was more significant for older people in a shorter time. This is the first study to provide evidence that the DEE may have antiaging effects and could be beneficial for older people.

Antibiotic exposure and asthma development in children with allergic rhinitis.

PURPOSE: Early-life antibiotic use may be associated with asthma, yet whether this association also exists in patients with allergic rhinitis (AR) remains unknown. We investigated the association between antibiotic exposure and asthma development in AR children. METHODS: AR patients less than 18 year-old were enrolled from the Taiwan National Health Insurance Database, which reported information from 2005 to 2010. The case group was defined as having newly developed asthma, and the control group was defined as never having an asthma diagnosis. The age of first exposure to antibiotic prescriptions and antibiotic exposure records preceding 5 years before the first asthma diagnosis were obtained from drug prescription records. The odds ratio (OR) was examined after adjusting for age, gender, resident urbanization, underlying medical disorders and medications. RESULTS: A total of 3236 AR patients with newly developed asthma and 9708 AR patients without asthma were included in this study. Antibiotic exposure before the age of 3 years was not associated with asthma development. Preceding 5-year antibiotic exposure increased the risk of asthma development with a dose-response relationship, even for antibiotics with low cumulative defined daily doses (adjusted OR 1.40, 95% CI 1.12-1.75). Preceding 5-year exposure to penicillin and macrolide significantly increased the risk of asthma when diagnosed before age 12 in AR patients, but this was not statistically significant when asthma diagnosed after age 12. CONCLUSION: Preceding 5-year antibiotic exposure, particularly to penicillin group of amoxicillin and macrolides, is associated with the risk of asthma development before age 12 in AR children.

The effect of NSAIDs exposure on breast cancer risk in female patients with autoimmune diseases.

Both breast cancer and autoimmune diseases (ADs) are predominant in women. NSAIDs are common medications for AD. Evidence on the association between NSAIDs use and breast cancer risk is controversial. We investigated the association between NSAIDs exposure and breast cancer risk in female patients with AD. AD patients older than 18 years of age were enrolled from Taiwan Longitudinal Health Insurance Database 2005. The NSAID users were defined as AD patients who had ever taken NSAIDs for at least 3 months between 2000 and 2009. All individuals were followed from the date of first diagnosis of AD to the end of 2013 to evaluate the risk of breast cancer. We estimated the adjusted hazard ratio (HR) using Cox proportional hazard regression after adjusting for age, comorbidities and medications. A total of 12 331 NSAID users and 12 331 non-NSAID users were included in this study after 1: 1 individual matching. The NSAID users were less likely to develop breast cancer than the non-NSAID users (adjusted HR: 0.37; 95% confidence interval: 0.27-0.50; P < 0.001), even if they used NSAIDs with low cumulative defined daily doses (adjusted HR: 0.42; 95% confidence interval: 0.34-0.53; P < 0.001). The incidence of new-onset breast cancer in NSAID users was significantly decreased in users taking selective cyclooxygenase 2 inhibitors, diclofenac, ibuprofen and piroxicam. Lower cumulative hazard rates were found in the AD patients who used NSAIDs (P < 0.001). NSAID exposure is associated with a decreased risk of breast cancer in female AD patients.

Effect of antibiotic use for acute bronchiolitis on new-onset asthma in children.

Early-life use of antibiotics is associated with asthma. We examined the effect of antibiotic use for early-life bronchiolitis on the development of new-onset asthma in children from Taiwan between 2005 and 2010. Data were from the National Health Insurance Research Database 2010, and diseases were coded using the International Classification of Disease (ICD). We classified the patients, all of whom had bronchiolitis, as having asthma or not having asthma. Asthma was diagnosed using ICD criteria and by use of an inhaled bronchodilator and/or corticosteroid twice in one year. We identified age at asthma onset, sex, residential area, history of atopy and NSAID use, age at first use of antibiotics, and the specific antibiotic, and adjusted for these factors using conditional logistic regression analysis. Among all individuals, there was a relationship between risk of new-onset asthma with use of a high dose of an antibiotic (adjusted odds ratio [aOR] = 3.33, 95% confidence interval [CI] = 2.67-4.15). Among the different antibiotics, macrolides (aOR = 2.87, 95% CI = 1.99-4.16), and azithromycin specifically (aOR = 3.45, 95% CI = 1.62-7.36), had the greatest effect of development of asthma.

Correction to: CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3-Methylglutaric Diazolides in MTBE.

The original version of this article unfortunately contained a mistake in Eq. 3.

CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3-Methylglutaric Diazolides in MTBE.

Optically pure 3-substituted glutarates can be prepared from the alcoholic ring-opening of cyclic anhydride derivatives, esterification of 3-substituted glutaric acid, and hydrolysis, alcoholysis, aminolysis, and ammonolysis of the diester derivatives via hydrolases or organocatalysts. Unfortunately, most of them mainly focus on the first-step desymmetrization, leading to the difficulty on producing optically pure enantiomers. As a general trend in lipase-catalyzed desymmetrization of 3-methylglutarates, poorer enantiomeric excesses with lower chemical yields were found, as the methyl substituent is relatively small to induce a high enzyme stereodiscrimination. The two-step desymmetrization for CALB-catalyzed alcoholysis of 3-methylglutaric di-1,2,4-triazolide 1a in anhydrous MTBE is first developed to increase the enzyme activity in each reaction step. The enantioselectivity for the second-step kinetic resolution is furthermore improved by using 3-methylglutaric dipyrazolide 1b as the substrate. The kinetic and thermodynamic analysis is, moreover, addressed for shedding insights into the desymmetrization process.

EBSD and electron channeling study of anomalous slip in oligocrystals of high chromium ferritic stainless steel.

In the present study, electron backscatter diffraction (EBSD) and electron channeling contrast imaging (ECCI) techniques were applied to investigate the deformation pattern of coarse ferrite grains after being subjected to 3%, 6%, and 10% tensile deformation. Oligocrystals of Crofer® 22H ferritic steel were obtained as experimental material at 1075°C for 22min annealing. Using kernel average misorientation (KAM) mapping obtained from EBSD, possible slip planes are (110), (101), (12-1) and (32-1) in grain A; (0-11), (-101), (-112), (1-21) in grain B; and (0-11), (1-21) and (11-2) in grain C. Combining ECCI and EBSD techniques enables us to identify two a0[11¯1]/2 edge dislocations that occur on the (110)[1-11] and (32-1)[1-11] slip systems for grain A, thereby breaking down Schmid's law.

Plasmonic Gold Nanorods Coverage Influence on Enhancement of the Photoluminescence of Two-Dimensional MoS2 Monolayer.

The 2-D transition metal dichalcogenide (TMD) semiconductors, has received great attention due to its excellent optical and electronic properties and potential applications in field-effect transistors, light emitting and sensing devices. Recently surface plasmon enhanced photoluminescence (PL) of the weak 2-D TMD atomic layers was developed to realize the potential optoelectronic devices. However, we noticed that the enhancement would not increase monotonically with increasing of metal plasmonic objects and the emission drop after the certain coverage. This study presents the optimized PL enhancement of a monolayer MoS2 in the presence of gold (Au) nanorods. A localized surface plasmon wave of Au nanorods that generated around the monolayer MoS2 can provide resonance wavelength overlapping with that of the MoS2 gain spectrum. These spatial and spectral overlapping between the localized surface plasmon polariton waves and that from MoS2 emission drastically enhanced the light emission from the MoS2 monolayer. We gave a simple model and physical interpretations to explain the phenomena. The plasmonic Au nanostructures approach provides a valuable avenue to enhancing the emitting efficiency of the 2-D nano-materials and their devices for the future optoelectronic devices and systems.

Synthesis, characterization and catalytic activity of lithium and sodium iminophenoxide complexes towards ring-opening polymerization of L-lactide.

A series of lithium and sodium iminophenoxide complexes have been successfully synthesized and characterized by X-ray crystallography and investigated as catalysts for the ring opening polymerization of L-lactide. The nature and steric bulk of the ligands coordinated to the central metal ions greatly influence the catalytic properties. Complexes with bidenate ligands exhibit higher catalytic activity than tridentate counterparts because the third coordination atom contends with L-lactide, which decreases activity. Oxygen is the third atom in the tridentate ligand, providing stronger chelation ability with Li and Na than nitrogen or sulfur and occupies the space with which L-lactide is coordinated.