Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2+-GFP+-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2+-GFP+-OPCs and transplanted them into the rats’ cervical 4–5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2+-GFP+-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2+-GFP+-OPCs primarily differentiated into adenomatous polyposis coli (APC+) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2+-GFP+-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2+-GFP+-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).
Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.
Clinical information about genotypically different clones of biofilm-producing Staphylococcus aureus is largely unknown. We examined whether different clones of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) differ with respect to staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) in biofilm formation. The study used 60 different types of spa and determined the phenotypes, the prevalence of the 13 MSCRAMM, and biofilm genes for each clone. The current investigation was carried out using a modified Congo red agar (MCRA), a microtiter plate assay (MPA), polymerase chain reaction (PCR), and reverse transcriptase polymerase chain reaction (RT-PCR). Clones belonging to the same spa type were found to have similar properties in adheringto the polystyrene microtiter plate surface. However, their ability to produce slime on MCRA medium was different. PCR experiments showed that 60 clones of MSSA and MRSA were positive for 5 genes (out of 9 MSCRAMM genes). icaADBC genes were found to be present in all the 60 clones tested indicating a high prevalence, and these genes were equally distributed among the clones associated with MSSA and those with MRSA. The prevalence of other MSCRAMM genes among MSSA and MRSA clones was found to be variable. MRSA and MSSA gene expression (MSCRAMM and icaADBC) was confirmed by RT-PCR.
The quest for universal memory is driving the rapid development of memories with superior all-round capabilities in non-volatility, high speed, high endurance and low power. Phase-change materials are highly promising in this respect. However, their contradictory speed and stability properties present a key challenge towards this ambition. We reveal that as the device size decreases, the phase-change mechanism changes from the material inherent crystallization mechanism (either nucleation- or growth-dominated), to the hetero-crystallization mechanism, which resulted in a significant increase in PCRAM speeds. Reducing the grain size can further increase the speed of phase-change. Such grain size effect on speed becomes increasingly significant at smaller device sizes. Together with the nano-thermal and electrical effects, fast phase-change, good stability and high endurance can be achieved. These findings lead to a feasible solution to achieve a universal memory.
The genus Rhodococcus has proved to be a promising option for the cleanup of polluted sites and application of a microbial biocatalyst. Rhodococcus sp. strain R04, isolated from oil-contaminated soil, can biodegrade polychlorinated biphenyls. Here we report the draft genome sequence of Rhodococcus sp. strain R04, which could be used to predict genes for xenobiotic biodegradation and provide important insights into the applications of this strain.
Prevalence of allergic diseases has increased in the last years. Data on recurrent wheezing (≥3 episodes) in infancy is scarce. The aim of this study was to verify changing in prevalence of recurrent wheezing infants in the south of Brazil.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) with questions: Has your baby had wheezing or whistling in the chest area or bronchitis in the first 12 months of life? Has your baby had 3 or more wheezing episodes in the first year of life? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between August 2005 to December 2006 (EISL Phase I) and September 2009 to September 2010 (EISL Phase III). Categorical variables are shown as proportion and differences verified by chi-square test, and continuous variables were expressed as mean ± SD and analyzed by Student t test.
Three thousand three parents of infants answered questionnaire in the EISL Phase I, and 45.4% had had at least one wheezing episode; 50.7% were male, and 22.6% had recurrent wheezing episode starting at 5.5 ± 3.1 months. Five years later, in the EISL Phase III, 1003 parents participated in the survey: 40.6% had at least one wheezing episode (P = 0.46), 51.1% were male, and 19.8% had recurrent wheezing (P = 0.1) starting at 6.1 ± 3 months (P = 0.06).
Recurrent wheezing in infancy is highly prevalent and starts early in life. In our population, recurrent wheezing rates did not modify in the time period of study.
There are controversies in treating recurrent wheezing (≥3 episodes) in pre-school children. The aim of this study was to verify changes in treatment of recurrent wheezing infants.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) that covers physician diagnosis of asthma, and frequency, severity, and treatment of wheezing episodes. Regarding treatment specific questions are: Has your baby been treated with inhaled short-acting β2-agonists by metered dose inhaler or nebulizer? Has your baby been treated with inhaled corticosteroids? Has your baby been treated with antileukotrienes? Has your baby been treated with oral corticosteroids? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between August/2005 to December/2006 (EISL Phase I) and September/2009 to September/2010 (EISL Phase III). Categorical variables are showed as proportion and differences verified by chi-square test.
Three thousand and 3 parents of infants answered questionnaire in the EISL Phase I and 22.6% had recurrent wheezing episodes. Five years later, in the EISL Phase III, 1003 parents participated in the survey and 19.8% had recurrent wheezing (P = 0.1). Inhaled short-acting β2-agonists continued to be prescribed in the same frequency (89.6% vs 86.5%, P = 0.21), however anti-asthmatic drugs were more used [antileukotrienes (6.9% vs 33%, P < 0.001), inhaled steroids (23.6% vs 37.5%, P = 0.001) and oral steroids (18.6% vs 26.5%, P = 0.01)] and doctor diagnosis of asthma has increased (16.2% vs 23%, P = 0.03). There were reductions on night-time symptoms (73% vs 61.5%, P = 0.001), severity (59.3% vs 42%, P = 0.001) and emergency room visits (69.3% vs 41.5%, P < 0.001) for recurrent wheezing infants, but no difference was seen in hospitalization (17.1% vs 12.5%, P = 0.12).
Recurrent wheezing treatment in infancy has increased in past years and may have contributed for reducing emergency room visits, night-time symptoms and severity for wheezing infants.
Paracetamol (PCM) and antibiotic (ATB) use have been associated with risk for wheezing and asthma in children. The aim of this study was to verify the association of recurrent wheezing (≥3 episodes) in infancy and use of ATB or PCM in the first year of life.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) with questions: Has your baby had wheezing or whistling in the chest area or bronchitis in the first 12 months of life? Has your baby had 3 or more wheezing episodes in the first year of life? How often has your baby used antibiotics in the first year of life? How often has your baby used paracetamol in the first year of life? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between September 2009 to September 2010 (EISL Phase III). Risk was demonstrated using Odds ratio and 95% CI.
One thousand and 3 parents participated in the survey and 19.8% of infants had recurrent wheezing starting at 6.1 ± 3 months. The use of PCM was not related to the presence of recurrent wheezing [No PCM (OR = 0.91; 95% CI, 0.38-2.19; P = 0.83), PCM 1–3 times (OR = 1.21; 95% CI, 0.77-1.91; P = 0.4), PCM 4–6 times (OR = 1.21; 95% CI, 0.77-1.9; P = 0.41) and PCM ≥7 times (OR = 0.76; 95% CI, 0.51-1.13; P = 0.17)], while more frequent use of ATB reduced the risk of recurrent wheezing in the first year of life [No ATB (OR = 2.18; 95% CI, 1.35-3.51; P = 0.001), ATB 1–3 times (OR = 1.39; 95% CI, 0.93-2.07; P = 0.1), ATB 4–6 times (OR = 0.37; 95% CI, 0.22-0.62; P = 0.001) and PCM≥7 times (OR = 0.22; 95% CI, 0.07-0.66; P = 0.001)].
The frequent use of ATB reduced the risk of recurrent wheezing in the first year of life unlike PCM that was not associated with recurrent wheezing in this study population.
We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis.
Arthrobacter; Bacillus; liquid chromatography mass spectrometry (LC-MS); N-acylhomoserine lactone; N-dodecanoyl-L-homoserine lactone; p-coumaroylhomoserine lactone; Pseudomonas frederiksbergensis; quorum quenching; quorum sensing; rapid resolution liquid chromatography (RRLC)
Diabetes is the sixth most common cause of death in the US and causes significant postoperative mortality and morbidity.
To characterize the impact of diabetes among patients undergoing surgery for colorectal cancer.
This is is a retrospective cohort study.
Patients in the Nationwide Inpatient Sample (NIS) who had undergone colorectal cancer surgery between 1998 and 2005.
Using multivariate regression, we determined the association of diabetes status with postoperative mortality, postoperative complications, and length of stay.
An estimated 218,534 patients had undergone surgery for colorectal cancer. We categorized subjects by the presence of diabetes, the prevalence of which was 15%. Crude postoperative in-hospital mortality was lower among diabetics compared to non-diabetics (2.5% vs. 3.2%, P < 0.0001). Adjusted mortality was 23% lower in those with diabetes compared to non-diabetics (aOR 0.77; 95% CI: 0.71–0.84). Diabetics also had lower adjusted post-operative complications compared to non-diabetics (aOR 0.82; 95% CI: 0.79–0.84). In uninsured individuals and patients <50 years of age, there was no protective association between diabetes and either in-hospital mortality or postoperative complications.
In patients undergoing colorectal cancer surgery, those with diabetes had a 23% lower mortality and fewer postoperative complications compared to non-diabetics. The mechanisms underlying this unexpected observation warrant further investigation.
diabetes; nationwide; colorectal cancer; hyperglycemia
Right-sided diaphragmatic rupture is less common and more difficult to diagnose than left-sided lesion. It is rarely combined with the herniation of the abdominal organs into the thorax. High level of suspicion is the key to early diagnosis, and a delay in diagnosis is implicated with a considerable risk of mortality and morbidity. We experienced a case of right-sided diaphragmatic rupture combined with complete avulsion of the right kidney and herniation of the liver into the thoracic cavity.
Diaphragm; Kidney; Liver; Trauma; Diaphragm, trauma
CTX-M-14-type extended-spectrum β-lactamase was first detected in Salmonella enterica serovar London strains which were isolated from three hospitalized pediatric patients with gastroenteritis. The isolates had pulsed-field gel electrophoresis patterns identical to those of the previously isolated antimicrobial-susceptible strains from community-acquired gastroenteritis, suggesting the susceptible clone acquired the resistance.
To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with ≥45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (≥20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.
Mass Screening; Lung Neoplasms; Tomography, Spiral Computed; Smoking
The paper reports a new method for three-dimensional observation of the location of focused particle streams along both the depth and width of the channel cross-section in spiral inertial microfluidic systems. The results confirm that particles are focused near the top and bottom walls of the microchannel cross-section, revealing clear insights on the focusing and separation mechanism. Based on this detailed understanding of the force balance, we introduce a novel spiral microchannel with a trapezoidal cross-section that generates stronger Dean vortices at the outer half of the channel. Experiments show that particles focusing in such device are sensitive to particle size and flow rate, and exhibits a sharp transition from the inner half to the outer half equilibrium positions at a size-dependent critical flow rate. As particle equilibration positions are well segregated based on different focusing mechanisms, a higher separation resolution is achieved over conventional spiral microchannels with rectangular cross-section.
Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.
Peptide ligands have played an important role in tumor-targeted drug delivery as targeting moieties. The in vivo fate of peptide-mediated drug delivery systems and the following antitumor effects may greatly depend on the stability of the peptide ligand. In the current study, a tumor-targeting cyclic peptide screened by phage display, Lyp-1 (a peptide that specifically binds to tumor and endothelial cells of tumor lymphatics in certain tumors), was structurally modified by replacement of the original intramolecular disulfide bond with a diseleno bond. The produced analog Syp-1 (seleno derivative of Lyp-1) maintained specific binding ability to the target protein p32 (Kd = 18.54 nM), which is similar to that of Lyp-1 (Kd = 10.59 nM), indicated by surface plasmon resonance assay. Compared with Lyp-1, Syp-1 showed significantly improved stability against serum. After the peptide attached onto the surface of fluorophore-encapsulating liposomes, the more efficient tumor uptake of liposomal fluorophore mediated by Syp-1 was observed. Furthermore, Syp-1 modified liposomal doxorubicin presented the most potent tumor growth inhibitory ability among all the therapeutic groups, with a low half maximal inhibitory concentration of 588 nM against MDA-MB-435 cells in vitro and a high tumor inhibition rate of 73.5% in vivo. These findings clearly indicated that Syp-1 was a stable and effective tumor targeting ligand and suggest that the sulfur-to-selenium replacement strategy may help stabilize the phage-displayed cyclic peptide containing disulfide-bond under physiological conditions and strongly support the validity of peptide-mediated drug targeting.
tumor targeting; liposome; cyclic peptide; selenopeptide
Methylphenidate (MPD) is a psychostimulant that enhances dopaminergic neurotransmission in the central nervous system by using mechanisms similar to cocaine and amphetamine. The mode of action of brain circuitry responsible for an animal’s neuronal response to MPD is not fully understood. The nucleus accumbens (NAc) has been implicated in regulating the rewarding effects of psychostimulants. The present study used permanently implanted microelectrodes to investigate the acute and chronic effects of MPD on the firing rates of NAc neuronal units in freely behaving rats. On experimental day 1 (ED1), following a saline injection (control), a 30 minute baseline neuronal recording was obtained immediately followed by a 2.5 mg/kg i.p. MPD injection and subsequent 60 min neuronal recording. Daily 2.5 mg/kg MPD injections were given on ED2 through ED6 followed by 3 washout days (ED7 to 9). On ED10, neuronal recordings were resumed from the same animal after a saline and MPD (rechallenge) injection exactly as obtained on ED1. Sixty-seven NAc neuronal units exhibited similar wave shape, form and amplitude on ED1 and ED10 and their firing rates were used for analysis. MPD administration on ED1 elicited firing rate increases and decreases in 54% of NAc units when compared to their baselines. Six consecutive MPD administrations altered the neuronal baseline firing rates of 85% of NAc units. MPD rechallenge on ED10 elicited significant changes in 63% of NAc units. These alterations in firing rates are hypothesized to be through mechanisms that include D1 and D2-like DA receptor induced cellular adaptation and homeostatic adaptations/deregulation caused by acute and chronic MPD administration.
Methylphenidate; Nucleus accumbens; Electrophysiology; Behavior sensitization/tolerance
To review the experience of surgical repair of post-infarction ventricular septal rupture (VSR) and analyze the associated outcomes and prognostic factors.
Following approval from the Singhealth Centralised Institutional Review Board (reference: 2011/881/C), a retrospective review was performed on 38 consecutive patients who had undergone surgical repair of post-infarction VSR between 1999 and 2011. Continuous variables were expressed as either mean ± standard deviation or median with 25th and 75th percentiles. These were compared using two-tailed t-test or Mann–Whitney U test respectively. Categorical variables were compared using chi-square or Fisher’s exact test. To identify predictors of operative mortality, univariate analysis of perioperative variables followed by multivariate analysis of significant univariate risk factors was performed. A two-tailed p-value < 0.05 was used to indicate statistical significance.
Mean age was 65.7 ± 9.4 years with 52.6% males. The VSR was anterior in 28 (73.7%) and posterior in 10 patients. Median interval from myocardial infarction to VSR was 1 day (1, 4). Pre-operative intra-aortic balloon pump was inserted in 37 patients (97.8%). Thirty-six patients (94.7%) underwent coronary angiography.
Thirty-five patients (92.1%) underwent patch repair. Mean aortic cross clamp time was 82 ± 40 minutes and mean cardiopulmonary bypass time was 152 ± 52 minutes. Coronary artery bypass grafting (CABG) was performed in 19 patients (50%), with a mean of 1.5 ± 0.7 distal anastomoses. Operative mortality within 30 days was 39.5%.
Univariate analysis identified emergency surgery, New York Heart Association (NYHA) class, inotropic support, right ventricular dysfunction, EuroSCORE II, intra-operative red cell transfusion, post-operative renal failure and renal replacement therapy (RRT) as predictors of operative mortality. Multivariate analysis identified NYHA class and post-operative RRT as predictors of operative mortality.
Ten year overall survival was 44.4 ± 8.4%. Right ventricular dysfunction, LVEF and NYHA class at presentation were independent factors affecting long-term survival. Concomitant CABG did not influence early or late survival.
Surgical repair of post-infarction VSR carries a high operative mortality. NYHA class at presentation and post-operative RRT are predictors of early mortality. Right ventricular dysfunction, LVEF and NYHA class at presentation affect long-term survival. Concomitant CABG does not improve survival.
Ventricular septal rupture; Myocardial infarction
There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.
Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.
Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).
NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.
Rehabilitation interventions promote functional recovery among frail older adults and little is known about the clinical significance of physical outcome measure changes. The purpose of our study is to examine the minimal clinically important difference (MCID) for the 6-minute walk distance (6MWD) among frail Asian older adults.
Data from the “Evaluation of the Frails’ Fall Efficacy by Comparing Treatments” study were analyzed. Distribution-based and anchor-based methods were used to estimate the MCID of the 6MWD. Participants who completed the trial rated their perceived change of overall health on the Global Rating of Change (GROC) scale. The receiver operating characteristic curve (ROC) was used to analyze the sensitivity and specificity of the cut-off values of 6MWD (in meters) for GROC rating of “a little bit better” (+2), based on feedback from participants.
The mean (SD) change in 6MWD was 37.3(46.2) m among those who perceived a change (GROC ≥ 2), while those who did not was 9.3(18.2) m post-intervention (P = 0.011). From the anchor-based method, the MCID value for the 6MWD was 17.8 m (sensitivity 56.7% and specificity 83.3%) while distribution-based method estimated 12.9 m.
The MCID estimate for 6MWD was 17.8 m in the moderately frail Asian older adults with a fear of falling. The results will aid the clinicians in goal setting for this patient population.
Australian New Zealand Clinical Trials Registry number: ACTRN12610000576022
6-minute walk distance; Minimal clinically important difference; Older adult
Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, we observed that HSM not only reduced expression of the inflammasome component NLRP1 and the P2X7R but also reduced the activation of caspase-4, and ATP-induced ROS production. These findings reveal that the HSM extract has anti-inflammatory properties attributed to its ability to inhibit both canonical and non-canonical inflammasomes.
Neaumycin, a new 30-membered macrolide featuring an internal diester bridge, a molecular architecture that is unprecedented among known macrolide natural products, was isolated from a soil actinomycete strain Streptomyces sp. neau-x211. The structure of neaumycin was elucidated on the basis of comprehensive mass and NMR spectroscopic interpretation, including the relative stereochemistry of four independent coupling systems.
Activation of the mTOR pathway subsequent to phosphatase and tensin homolog (PTEN) mutation may be associated with glucocorticoid (GC) resistance in acute lymphoblastic leukemia (ALL). The combination activity of rapamycin and dexamethasone in cell lines and xenograft models of ALL was determined. Compared with either drug alone, dexamethasone + rapamycin showed significantly greater apoptosis and cell cycle arrest in some cell lines, which was more frequently seen in T-lineage cell lines with PTEN mutation. The combination significantly extended the event-free survival of mice carrying PTEN mutated xenografts. Our data suggest that PI3K/mTOR pathway inhibitors could benefit patients with PTEN mutated T-ALL.
dexamethasone; rapamycin; acute lymphoblastic leukemia
Chinese bayberry fruit is a rich source of anthocyanins, especially cyanidin-3-glucoside (C3G). The present study investigated the protective effects of C3G-rich bayberry fruit extract (CRBFE) against pancreatic β cells against oxidative stress–induced injury as well as its hypoglycemic effect in diabetic mice. Bayberry extract from “Biqi” was used for both in vitro and in vivo testing because of its high C3G content and high antioxidant capacity. Pretreatment of β cells with CRBFE (containing 0.5 μmol/L C3G) prevented cell death, increased cellular viability, and decreased mitochondrial reactive oxygen species production and cell necrosis induced by 800 or 1,200 μmol/L H2O2. CRBFE dose-dependently up-regulated pancreatic duodenal homeobox 1 gene expression, contributing to increased insulin-like growth factor II gene transcript levels and insulin protein in INS-1 cells. In addition, administration of CRBFE (150 μg of C3G/10 g of body weight twice per day) significantly reduced blood glucose in streptozotocin-induced diabetic ICR mice and increased the glucose tolerance in an oral glucose tolerance test (P<.05). Such results indicated that CRBFE might be useful in prevention and control of diabetes mellitus and diabetes-associated complications.
anthocyanins; antioxidants; diabetes; fruit extract; oxidative stress