Efficacy and Safety of Intracoronary versus Intravenous Administration of Tirofiban during Percutaneous Coronary Intervention for Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

Background

Percutaneous coronary intervention (PCI) is known as the most effective treatment for acute coronary syndrome (ACS). However, without proper therapy and patient management, stent thrombosis after PCI may lead to another myocardial infarction. In addition to aspirin and clopidogrel, tirofiban is often used as an antiplatelet therapy in patients with ACS. To date, there has been no comprehensive evaluation of the efficacy and safety of intracoronary (IC) tirofiban administration for ACS patients undergoing PCI compared with intravenous (IV) administration. Therefore, this meta-analysis was conducted to investigate the clinical efficiency and safety of IC versus intravenous (IV) tirofiban in ACS patients undergoing PCI.

Methods

We searched PubMed and Medline for randomized controlled trials (RCTs) comparing IC versus IV administration of tirofiban in ACS patients undergoing PCI. We evaluated the effects of tirofiban on thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI, TIMI myocardial perfusion grade 3 (TMP grade 3), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACE), target vessel revascularization (TVR), death, reinfarction and adverse drug effects (specifically bleeding events).

Results

Seven trials involving 1,027 patients were included in this meta-analysis. IC administration of tirofiban significantly increased TIMI grade 3 flow (OR 2.11; 95% CI 1.02 to 4.37; P = 0.04) and TMP grade 3 (OR 2.67; 95% CI 1.09 to 6.49; P = 0.03, I² = 64%) while reducing MACE (OR 0.46, 95% CI: 0.28 to 0.75; P = 0.002) compared with IV administration of tirofiban. No significant differences were observed in the occurrence of TVR, death, reinfarction and the incidence of bleeding events between the two groups.

Conclusions

This meta-analysis supports the use of IC over IV administration of tirofiban in patients with ACS to improve TIMI flow, TMP flow and MACE. However, there was no statistically significant difference in the risk of bleeding complications between the two groups.     

The effects of acylation stimulating protein supplementation <Emphasis Type="Italic">VS</Emphasis> antibody neutralization on energy expenditure in wildtype mice

Background  

Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure.     

Para‐psychobiotic Lactobacillus gasseri CP2305 ameliorates stress‐related symptoms and sleep quality

Aims

To confirm the stress‐relieving effects of heat‐inactivated, enteric‐colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course.

Methods and Results

Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress‐related somatic symptoms and sleep quality respectively. The aggravation of stress‐associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea‐like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex‐related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation.

Conclusions

CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s).

Significance and Impact of the Study

This study characterizes the effects of a stress‐relieving para‐psychobiotic in humans.     

<Emphasis Type="Italic">Arabidopsis</Emphasis> ETO1 specifically interacts with and negatively regulates type 2 1-aminocyclopropane-1-carboxylate synthases

Background  

In Arabidopsis, ETO1 (ETHYLENE-OVERPRODUCER1) is a negative regulator of ethylene evolution by interacting with AtACS5, an isoform of the rate-limiting enzyme, 1-aminocyclopropane-1-carboxylate synthases (ACC synthase or ACS), in ethylene biosynthetic pathway. ETO1 directly inhibits the enzymatic activity of AtACS5. In addition, a specific interaction between ETO1 and AtCUL3, a constituent of a new type of E3 ubiquitin ligase complex, suggests the molecular mechanism in promoting AtACS5 degradation by the proteasome-dependent pathway. Because orthologous sequences to ETO1 are found in many plant species including tomato, we transformed tomato with Arabidopsis ETO1 to evaluate its ability to suppress ethylene production in tomato fruits.     

Equol an isoflavonoid: potential for improved prostate health, <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>evidence

Background  

To determine: in vitro binding affinity of equol for 5alpha-dihydrotestosterone (5alpha-DHT), in vitro effects of equol treatment in human prostate cancer (LNCap) cells, and in vivo effects of equol on rat prostate weight and circulating levels of sex steroid hormones.     

Atopic dermatitis‐mitigating effects of new Lactobacillus strain,Lactobacillus sakei probio 65 isolated from Kimchi

Aims

Atopic dermatitis (AD) is an inflammatory skin disease. Probiotics have been reported to modulate immune responses and thus are now being suggested as potential treatments for allergies. In this study, we investigated the inhibitory effects of Lactobacillus sakei probio 65 isolated from Kimchi on artificially inducing AD in NC/Nga mice.

Methods and Results

Oral administration of viable or heat‐inactivated Lact. sakei probio 65 improved the condition of skin and reduced scratching frequency. Serum levels of IgE and cutaneous T‐cell‐attracting chemokine (CTACK) were significantly decreased by this therapy. Dead Lact. sakei probio 65 also decreased IL‐4 and IL‐6 serum concentrations. Moreover, both live and dead Lact. sakei probio 65 inhibited the expression of Thymus and activation‐regulated chemokine and CTACK in AD‐like skin lesions. The increased levels of Foxp3 expression in the lesional skin and ears were also suppressed by Lact. sakei probio 65. In addition, Lact. sakei probio 65 inhibited β‐hexosaminidase release and the secretion of IL‐4, TNF‐α and IL‐6 from RBL‐2H3 cells.

Conclusions

Oral treatment with both viable and heat‐inactivated Lact. sakei probio 65 inhibits skin inflammation and AD‐like skin lesions, as well as mast cell activation.

Significance and Impact of the Study

Lactobacillus sakei probio 65 has an inhibitory effect on atopic dermatitis‐like skin lesions and may represent an effective new anti‐inflammatory agent.     

N-acetylcysteine inhibit biofilms produced by <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

Background  

Pseudomonas aeruginosa is a common pathogen in chronic respiratory tract infections. It typically makes a biofilm, which makes treatment of these infections difficult. In this study, we investigated the inhibitory effects of N-acetylcysteine (NAC) on biofilms produced by P. aeruginosa.     

Hesperetin-7,3'-<Emphasis Type="Italic">O</Emphasis>-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

Background  

Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD).     

Hormonal induction of gamete release,and in-vitro fertilisation,in the critically endangered Southern Corroboree Frog, <Emphasis Type="Italic">Pseudophryne corroboree</Emphasis>

Background  

Conservation Breeding Programs (CBP's) are playing an important role in the protection of critically endangered anuran amphibians, but for many species recruitment is not successful enough to maintain captive populations, or provide individuals for release. In response, there has been an increasing focus on the use of Assisted Reproductive Technologies (ART), including the administration of reproductive hormones to induce gamete release followed by in vitro fertilisation. The objective of this study was to test the efficacy of two exogenous hormones to induce gamete release, for the purpose of conducting in vitro fertilisation (IVF), in one of Australia's most critically endangered frog species, Pseudophryne corroboree.     

Two acetyl-CoA synthetase isoenzymes are encoded by distinct genes in marine yeast <Emphasis Type="Italic">Rhodosporidium diobovatum</Emphasis>

Objectives

Two genes encoding two acetyl-CoA synthetase (ACS) isoenzymes have been identified in the marine yeast Rhodosporidium diobovatum MCCC 2A00023.

Results

ACS1 encoded a polypeptide with a sequence of 578 amino acid residues, a predicted molecular weight of 63.73 kDa, and pI of 8.14, while the ACS2 encoded a polypeptide containing 676 amino acid residues with a deduced molecular mass of 75.61 kDa and a pI of 5.95. Biological activity of Acs1p and Acs2p was confirmed by heterologous expression in Escherichia coli. A 1.5-kb DNA fragment of the ACS1 gene and a 2.7-kb DNA fragment of the ACS2 gene were deleted using the RNA guide CRISPR-Cas9 system. The strain lacking ACS1 was unable to grow on acetate and ethanol media, while the ACS2 deletant was unable to grow on glucose medium. ACS1-ACS2 double mutants of R. diobovatum were non-viable.

Conclusions

ACS isoenzymes are essential to the yeast metabolism, and other sources of ACSs cannot compensate for the lack of ACSs encoded by the two genes.

     

<Emphasis Type="Italic">Glycine tomentella</Emphasis> Hayata inhibits IL-1β and IL-6 production,inhibits MMP-9 activity,and enhances RAW264.7 macrophage clearance of apoptotic cells

Background  

To assess the effects of Glycine tomentella Hayata (GTH), a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages.     

Herd prevalence of Enterobacteriaceae producing CTX‐M‐type and CMY‐2 β‐lactamases among Japanese dairy farms

Aims

To determine the herd prevalence of Enterobacteriaceae producing CTX‐M‐type extended‐spectrum β‐lactamases (ESBLs) among 381 dairy farms in Japan.

Methods and Results

Between 2007 and 2009, we screened 897 faecal samples using BTB lactose agar plates containing cefotaxime (2 μg ml^?1). Positive isolates were tested using ESBL confirmatory tests, PCR and sequencing for CTX‐M, AmpC, TEM and SHV. The incidence of Enterobacteriaceae producing CTX‐M‐15 (n = 7), CTX‐M‐2 (n = 12), CTX‐M‐14 (n = 3), CMY‐2 (n = 2) or CTX‐M‐15/2/14 and CMY‐2 (n = 4) in bovine faeces was 28/897 (3·1%) faecal samples. These genes had spread to Escherichia coli (n = 23) and three genera of Enterobacteriaceae (n = 5). Herd prevalence was found to be 20/381 (5·2%) dairy farms. The 23 E. coli isolates showed clonal diversity, as assessed by multilocus sequence typing and pulsed‐field gel electrophoresis. The pandemic E. coli strain ST131 producing CTX‐M‐15 or CTX‐M‐27 was not detected.

Conclusions

Three clusters of CTX‐M (CTX‐M‐15, CTX‐M‐2, CTX‐M‐14) had spread among Japanese dairy farms.

Significance and Impact of the Study

This is the first report on the prevalence of multidrug‐resistant CTX‐M‐15–producing E. coli among Japanese dairy farms.     

Manufacturing and <Emphasis Type="Italic">in vivo</Emphasis> inner ear visualization of MRI traceable liposome nanoparticles encapsulating gadolinium

Background  

Treatment of inner ear diseases remains a problem because of limited passage through the blood-inner ear barriers and lack of control with the delivery of treatment agents by intravenous or oral administration. As a minimally-invasive approach, intratympanic delivery of multifunctional nanoparticles (MFNPs) carrying genes or drugs to the inner ear is a future therapy for treating inner ear diseases, including sensorineural hearing loss (SNHL) and Meniere's disease. In an attempt to track the dynamics and distribution of nanoparticles in vivo, here we describe manufacturing MRI traceable liposome nanoparticles by encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) (abbreviated as LPS+Gd-DOTA) and their distribution in the inner ear after either intratympanic or intracochlear administration.     

Genome scale prediction of substrate specificity for acyl adenylate superfamily of enzymes based on active site residue profiles

Background  

Enzymes belonging to acyl:CoA synthetase (ACS) superfamily activate wide variety of substrates and play major role in increasing the structural and functional diversity of various secondary metabolites in microbes and plants. However, due to the large sequence divergence within the superfamily, it is difficult to predict their substrate preference by annotation transfer from the closest homolog. Therefore, a large number of ACS sequences present in public databases lack any functional annotation at the level of substrate specificity. Recently, several examples have been reported where the enzymes showing high sequence similarity to luciferases or coumarate:CoA ligases have been surprisingly found to activate fatty acyl substrates in experimental studies. In this work, we have investigated the relationship between the substrate specificity of ACS and their sequence/structural features, and developed a novel computational protocol for in silico assignment of substrate preference.     

Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori‐infected subjects: A randomized,double‐blind placebo‐controlled clinical trial

Background

Burdock complex (BC) constitutes of burdock (Arctium lappa), angelica (Angelica sinensis), gromwell (Lithospermum erythrorhizon), and sesame (Sesamum indicum) oil, which are commonly used in traditional Chinese medicine (TCM) for treating various disorders. This study intended to examine the anti‐H. pylori activity of BC on AGS cell model as well as in asymptomatic H. pylori‐infected subjects.

Materials and Methods

AGS cell incubated with H. pylori and treated with BC to evaluate the minimum inhibition concentration (MIC), cell viability (MTT) anti‐adhesion activity, and inflammatory markers. In case of clinical trial, H. pylori‐positive subjects (urea breath test [UBT] >10%, n = 36) were enrolled and requested to intake BC (n = 19) or placebo (n = 17) for 8 weeks. Antioxidant capacity, total phenol, UBT, inflammatory markers were analyzed at the initial, 4th, 8th, and 10th weeks. Moreover, the endoscopic examination was carried out on baseline and 10th week.

Results

In vitro studies showed that BC treatment significantly inhibited (P < .05) the inflammatory markers and adhesion of H. pylori to AGS cell. However, H. pylori‐infected subject ingested with BC for 8 weeks significantly decreased (P < .05) the UBT value, inflammatory markers with improved antioxidant activity, and phenolic levels as compared to placebo. Also, consumption of BC considerably healed the ulcer wound.

Conclusion

Overall, the BC could attenuate H. pylori infection by inhibiting H. pylori adhesion and subsequent inflammatory response on the gastric epithelial cell (AGS) as well as clinically ameliorated UBT, antioxidant capacity, and alleviated inflammation to display its anti‐H. pylori activity.     

Acetic acid increases the phage-encoded enterotoxin A expression in <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Background  

The effects of acetic acid, a common food preservative, on the bacteriophage-encoded enterotoxin A (SEA) expression and production in Staphylococcus aureus was investigated in pH-controlled batch cultures carried out at pH 7.0, 6.5, 6.0, 5.5, 5.0, and 4.5. Also, genomic analysis of S. aureus strains carrying sea was performed to map differences within the gene and in the temperate phage carrying sea.     

Mitogen‐activated protein kinase 3 and 6 regulate Botrytis cinerea‐induced ethylene production in Arabidopsis

Plants challenged by pathogens, especially necrotrophic fungi such as Botrytis cinerea, produce high levels of ethylene. At present, the signaling pathways underlying the induction of ethylene after pathogen infection are largely unknown. MPK6, an Arabidopsis stress‐responsive mitogen‐activated protein kinase (MAPK) was previously shown to regulate the stability of ACS2 and ACS6, two type I ACS isozymes (1‐amino‐cyclopropane‐1‐carboxylic acid synthase). Phosphorylation of ACS2 and ACS6 by MPK6 prevents rapid degradation of ACS2/ACS6 by the 26S proteasome pathway, resulting in an increase in cellular ACS activity and ethylene biosynthesis. Here, we show that MPK3, which shares high homology and common upstream MAPK kinases with MPK6, is also capable of phosphorylating ACS2 and ACS6. In the mpk3 mutant background, ethylene production in gain‐of‐function GVG‐NtMEK2^DD transgenic plants was compromised, suggesting that MPK6 and MPK3 function together to stabilize ACS2 and ACS6. Using a liquid‐cultured seedling system, we found that B. cinerea‐induced ethylene biosynthesis was greatly compromised in mpk3/mpk6 double mutant seedlings. In contrast, ethylene production decreased only slightly in the mpk6 single mutant and not at all in the mpk3 single mutant, demonstrating overlapping roles for these two highly homologous MAPKs in pathogen‐induced ethylene induction. Consistent with the role of MPK3/MPK6 in the process, mutation of ACS2 and ACS6, two genes encoding downstream substrates of MPK3/MPK6, also reduced B. cinerea‐induced ethylene production. The residual levels of ethylene induction in the acs2/acs6 double mutant suggest the involvement of additional ACS isoforms, possibly regulated by MAPK‐independent pathway(s).     

Redox stress proteins are involved in adaptation response of the hyperthermoacidophilic archaeon <Emphasis Type="Italic">Sulfolobus solfataricus</Emphasis> to nickel challenge

Background  

Exposure to nickel (Ni) and its chemical derivatives has been associated with severe health effects in human. On the contrary, poor knowledge has been acquired on target physiological processes or molecular mechanisms of this metal in model organisms, including Bacteria and Archaea. In this study, we describe an analysis focused at identifying proteins involved in the recovery of the archaeon Sulfolobus solfataricus strain MT4 from Ni-induced stress.     

Effects of extracellular DNA and DNA‐binding protein on the development of a Streptococcus intermedius biofilm

Aims

The aim of this study was to clarify the effects of homologous and heterologous extracellular DNAs (eDNAs) and histone‐like DNA‐binding protein (HLP) on Streptococcus intermedius biofilm development and rigidity.

Methods and Results

Formed biofilm mass was measured with 0·1% crystal violet staining method and observed with a scanning electron microscope. The localizations of eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining with 7‐hydoxyl‐9H‐(1,3‐dichloro‐9,9‐dimethylacridin‐2‐one) and anti‐HLP antibody without fixation, respectively. DNase I treatment (200 U ml^?1) markedly decreased biofilm formation and cell density in biofilms. Colocalization of eHLP and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 μg ml^?1) purified from Strep. intermedius, other Gram‐positive bacteria, Gram‐negative bacteria, or human KB cells into the Strep. intermedius culture increased the biofilm mass of all tested strains of Strep. intermedius, wild‐type, HLP‐downregulated strain and control strains. In contrast, the addition of eDNA (>1 μg ml^?1) decreased the biofilm mass of all Strep. intermedius strains.

Conclusions

These findings demonstrated that eDNA and eHLP play crucial roles in biofilm development and its rigidity.

Significance and Impact of the Study

eDNA‐ and HLP‐targeting strategies may be applicable to novel treatments for bacterial biofilm‐related infectious diseases.     

Possible role of eclosion rhythm in mediating the effects of light-dark environments on pre-adult development in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

In insects, circadian clocks have been implicated in affecting life history traits such as pre-adult development time and adult lifespan. Studies on the period (per) mutants of Drosophila melanogaster, and laboratory-selected lines of Bactrocera cucurbitae suggested a close link between circadian clocks and development time. There is a possibility of clock genes having pleiotropic effects on clock period and pre-adult development time. In order to avoid such pleiotropic effects we have used wild type flies of same genotype under environments of different periodicities, which phenotypically either speeded up or slowed down the eclosion clock of D. melanogaster.