Theileria and Anaplasma are especially important emerging tick-borne pathogens of animals and humans. Molecular surveys and identification of the infectious agents in Mongolian gazelle, Procapra gutturosa are not only crucial for the species’ preservation, but also provide valuable information on parasite and bacterial epidemiology.
A molecular surveillance study was undertaken to assess the prevalence of Theileria spp. and Anaplasma spp. in P. gutturosa by PCR in China. Theileria luwenshuni, A. bovis, A. phagocytophilum, and A. ovis were frequently found in P. gutturosa in China, at a prevalence of 97.8%, 78.3%, 65.2%, and 52.2%, respectively. The prevalence of each pathogens in the tick Haemaphysalis longicornis was 80.0%, 66.7%, 76.7%, and 0%, respectively, and in the tick Dermacentor niveus was 88.2%, 35.3%, 88.2%, and 58.5%, respectively. No other Theileria or Anaplasma species was found in these samples. Rickettsia raoultii was detected for the first time in P. gutturosa in China.
Our results extend our understanding of the epidemiology of theileriosis and anaplasmosis in P. gutturosa, and will facilitate the implementation of measures to control these tick-borne diseases in China.
Theileria; Anaplasma; Detection; Procapra gutturosa; PCR; China
Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following co-exposures with the theory being that the agents may exert synergistic actions which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBC), measured by a direct plaque forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following four days of PAH and/or arsenic treatment. However, the TDAR response demonstrated suppression by both PAHs or arsenic in a concentration-dependent manner. p53 was also induced by NaAsO2 (As+3) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO2, As+3) was found to produce immunosuppression at concentrations as low as 0.5 µM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na2HAsO4, As+5). Co-exposure of spleen cell cultures to PAHs and As+3, both at individual low-effect concentrations, was found to produce profound suppression of the TDAR demonstrating synergy between these two chemical classes of agents.
immunotoxicity; PAHs; arsenic; synergy; TDAR
To study the influence of acupuncture and its possible mechanism on white adipose tissue of high fat diet-induced obese.
Four-week-old C57BL/6 J mice were randomly divided into a normal diet group and a high-fat diet (HFD) group. After 8 weeks, the HFD mice were randomly divided into Electro-acupuncture (EA) group and control group. Mice in the EA group were electro-acupunctured, under physical restraint, on Zusanli (ST36) and Neiting (ST44) acupoints, while the mice in the control group were under physical restraint only. Body weight and food intake were monitored, and serum leptin, cholesterol and triglyceride levels were measured by using biochemistrical methods. The effect of EA on white adipose tissues (WAT) was assessed by qPCR, immunobloting, immunohistochemistry (IHC), immunoprecipitation and cold endurance experiment.
The WAT/body weight ratio decreased (P < 0.05) in the EA group, albeit no significant difference on food consumption between EA and control groups. The difference in the darkness of Epi-WAT between EA and control groups could be distinguished visually. HE staining indicated that the EA mice had an increased number of UCP1-immunoreactive paucilocular adipocytes in their WAT. The expressions of brown adipose tissue (BAT) markers, including UCP1, COX4il and Nrtf1 were increased in the WAT of EA mice, acetylation of Pparγ was decreased by electro-acupuncture.
EA can remodel WAT to BAT through inducing UCP1 expression, and this may be one of the mechanisms by which acupuncture affects weight loss.
Acupuncture; Browning; Obesity; UCP1; White adipose tissue
The bone metastasis appeared early before the bone imaging for most of the above patients. 99Tcm-MDP (99Tcm marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of 99Tcm-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi 99Tcm-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, 99Tcm-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.
99Tcm-MDP; SPECT/CT; SPECT/MRI; integrated image; bone metastases
Alcanivorax sp. strain 97CO-5 was isolated from a crude-oil-degrading consortium, enriched from Yellow Sea sediment of China. Here, we present the draft genome of strain 97CO-5, which comprises 3,251,558 bp with a G+C content of 54.54% and contains 2,962 protein-coding genes and 42 tRNAs.
Following nitric oxide (nitrogen monoxide) and carbon monoxide, hydrogen sulfide (or its newer systematic name sulfane, H2S) became the third small molecule that can be both toxic and beneficial depending on the concentration. In spite of its impressive therapeutic potential, the underlying mechanisms for its beneficial effects remain unclear. Any novel mechanism has to obey fundamental chemical principles. H2S chemistry was studied long before its biological relevance was discovered, however, with a few exceptions, these past works have received relatively little attention in the path of exploring the mechanistic conundrum of H2S biological functions. This review calls attention to the basic physical and chemical properties of H2S, focuses on the chemistry between H2S and its three potential biological targets: oxidants, metals and thiol derivatives, discusses the applications of these basics into H2S biology and methodology, and introduces the standard terminology to this youthful field.
hydrogen sulfide; sulfane; sulfhydration; oxidants; metal; transsulfuration
Previously, we reported an improvement in the transfection efficiency of the plasmid DNA-chitosan (pDNA/CS) complex by the utilization of phosphorylatable short peptide-conjugated chitosan (pSP-CS). In this study, we investigated the effects of pSP-CS-mediated gene transfection of interleukin-1 receptor antagonist protein (IL-1Ra) combined with insulin-like growth factor-1 (IGF-1) in rabbit chondrocytes and in a rabbit model of cartilage defects. pBudCE4.1-IL-1Ra+igf-1, pBudCE4.1-IL-1Ra and pBudCE4.1-igf-1 were constructed and combined with pSP-CS to form pDNA/pSP-CS complexes. These complexes were transfected into rabbit primary chondrocytes or injected into the joint cavity. Seven weeks after treatment, all rabbits were sacrificed and analyzed. High levels of IL-1Ra and igf-1 expression were detected both in the cell culture supernatant and in the synovial fluid. In vitro, the transgenic complexes caused significant proliferation of chondrocytes, promotion of glycosaminoglycan (GAG) and collagen II synthesis, and inhibition of chondrocyte apoptosis and nitric oxide (NO) synthesis. In vivo, the exogenous genes resulted in increased collagen II synthesis and reduced NO and GAG concentrations in the synovial fluid; histological studies revealed that pDNA/pSP-CS treatment resulted in varying degrees of hyaline-like cartilage repair and Mankin score decrease. The co-expression of both genes produced greater effects than each single gene alone both in vitro and in vivo. The results suggest that pSP-CS is a good candidate for use in gene therapy for the treatment of cartilage defects and that igf-1 and IL-1Ra co-expression produces promising biologic effects on cartilage defects.
Many terpenoids have important pharmacological activity and commercial value; however, application of these terpenoids is often limited by problems associated with the production of sufficient amounts of these molecules. The use of Saccharomyces cerevisiae (S. cerevisiae) for the production of heterologous terpenoids has achieved some success. The objective of this study was to identify S. cerevisiae knockout targets for improving the synthesis of heterologous terpeniods. On the basis of computational analysis of the S. cerevisiae metabolic network, we identified the knockout sites with the potential to promote terpenoid production and the corresponding single mutant was constructed by molecular manipulations. The growth rates of these strains were measured and the results indicated that the gene deletion had no adverse effects. Using the expression of amorphadiene biosynthesis as a testing model, the gene deletion was assessed for its effect on the production of exogenous terpenoids. The results showed that the dysfunction of most genes led to increased production of amorphadiene. The yield of amorphadiene produced by most single mutants was 8–10-fold greater compared to the wild type, indicating that the knockout sites can be engineered to promote the synthesis of exogenous terpenoids.
Sumoylation is a recently described post-translational modification and only a few sumoylated neurotransmitter receptors are known. Through the present studies, we discovered that serotonin1A receptors (5-HT1A-Rs) can be sumoylated by SUMO1 (Small-Ubiquitin-related modifier 1) protein. The SUMO1-5-HT1A-R is ∼ 55kD, is located in the membrane fraction, but not the cytosol, and is distributed in all of the brain regions expressing 5-HT1A-Rs examined. Acute stimulation of 5-HT1A-Rs significantly increased SUMO1-5-HT1A-R in rat hypothalamus. Pre-treatment with estradiol for 2 days, which causes a partial desensitization of 5-HT1A-R signaling, potentiated agonistinduced increases in SUMO1-5-HT1A-Rs in the hypothalamus of ovariectomized rats. Using discontinuous gradient centrifugation followed by digitonin treatment, we found that the majority of SUMO1-5-HT1A-Rs is co-localized with endoplasmic-reticulum and trans-Golgi-network markers. Although a small proportion of SUMO1-5-HT1A-Rs are located in the detergent resistant microdomain (DRM) that contain active G-protein coupled receptors, their distribution was different from that of the Gαz protein that couples to the receptors. These data suggest that the SUMO1-5-HT1A-Rs are an inactive form of 5-HT1A-Rs, a finding further supported by results showing minimal 5-HT1A-R agonist binding to SUMO1-5-HT1A-Rs. Furthermore, SUMO1-5-HT1A-Rs in the DRM were increased by treatment with a 5-HT1A-R agonist, 8-OH-DPAT ((+)8-hydroxy-2-dipropylaminotetralin). Together, these data suggest that sumoylation of 5-HT1A-Rs may be related to 5-HT1A-R trafficking and internalization, which may contribute to 5-HT1A-R desensitization. Since 5-HT1A-Rs play an important role in mood regulation, the present results significantly impact on the understanding of the pathogenesis of affective disorders and development of better therapeutic approaches for these diseases.
SUMO1; endoplasmic reticulum; lipid raft; estradiol; fluoxetine; hypothalamus
Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects.
To test 16 previously-hypothesized associations between specific antihistamines and specific birth defects, and identify possible new associations.
We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within six months of delivery about demographic, reproductive, medical, and behavioral factors, and details on use of prescription and non-prescription medications. We compared 1st trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6,982 non-malformed controls, using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use.
Overall, 13.7% of controls were exposed to antihistamines during the 1st trimester. The most commonly-used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). Where estimates were stable, none supported the previously-hypothesized associations. Among over 100 exploratory comparisons of other specific antihistamine/defect pairs, 14 had ORs ≥1.5 of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons.
Our findings do not provide meaningful support for previously-posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation which may also apply to our new findings.
Antihistamines; birth defects; first trimester; maternal exposure
Background and Purpose
Phosphorylation of eNOS, an important post-translational modulator of its enzymatic activity, is reduced in diabetes. We hypothesized that modulation of eNOS phosphorylation could overcome diabetic vascular dysfunction and improves the outcome to stroke.
We used the db/db mouse model of type 2 diabetes. We mated db/db mice with eNOS knockin mice that carry single-amino acid mutations at the S1176 phosphorylation site; the phosphomimetic SD mutation shows increased eNOS enzymatic activity, while the unphosphorylatable SA mutation shows decreased eNOS activity. We characterized the vascular anatomy, baseline physiologic parameters and vascular reactivity. We used the middle cerebral artery occlusion model of stroke and measured infarct volume and neurological deficits.
db/db mice showed diminished eNOS phosphorylation at S1176. eNOS SD and SA mutations do not change the vascular anatomy at the Circle of Willis, brain capillary density, heart rate, or arterial blood gases of db/db mice. The eNOS SD mutation, but not the SA mutation, lowers blood pressure and improves vascular reactivity to acetylcholine in db/db mice. The eNOS SD mutation reduces stroke size and neurologic deficit following middle cerebral artery occlusion.
Diminished eNOS phosphorylation is a mechanism of vascular dysfunction in db/db mice. We show here that modulation of the eNOS S1176 phosphorylation site in db/db mice is associated with improved vascular reactivity and improved outcome to stroke following middle cerebral artery occlusion.
nitric oxide; endothelial dysfunction; diabetes mellitus
Ultrasound current source density imaging (UCSDI) is a noninvasive technique for mapping electric current fields in 4D (space + time) with the resolution of ultrasound imaging. This approach can potentially overcome limitations of conventional electrical mapping procedures often used during treatment of cardiac arrhythmia or epilepsy. However, at physiologic currents, the detected acoustoelectric (AE) interaction signal in tissue is very weak. In this work, we evaluated coded ultrasound excitation (chirps) for improving the sensitivity of UCSDI for mapping the electrocardiogram (ECG) in a live rabbit heart preparation. Results confirmed that chirps improved detection of the AE signal by as much as 6.1 dB compared to a square pulse. We further demonstrated mapping the ECG using a clinical intracardiac catheter, 1 MHz ultrasound transducer and coded excitation. B-mode pulse echo and UCSDI revealed regions of high current flow in the heart wall during the peak of the ECG. These improvements to UCSDI are important steps towards translation of this new technology to the clinic for rapidly mapping the cardiac activation wave.
acoustoelectric; cardiac arrhythmia mapping; ECG; coded excitation chirps
A new Early Eocene tapiromorph, Meridiolophus expansus gen. et sp. nov., from the Sanshui Basin, Guangdong Province, China, is described and discussed. It is the first reported Eocene mammal from the basin. The new taxon, represented by a left fragmentary mandible, is characterized by an expanded anterior symphyseal region, a long diastema between c1 and p1, a rather short diastema between p1 and p2, smaller premolars relative to molars, an incipient metaconid appressed to the protoconid on p3, a prominent entoconid on p4, molar metaconid not twinned, cristid obliqua extending mesially and slightly lingually from the hypoconid, inclined metalophid and hypolophid, and small hypoconulid on the lower preultimate molars. Meridiolophus is morphologically intermediate between basal Homogalax-like taxa and derived tapiromorphs (such as Heptodon). Phylogenetic analysis indicates Equidae is more closely related to Tapiromorpha than to Palaeotheriidae, although the latter is only represented by a single species Pachynolophus eulaliensis. ‘Isectolophidae’, with exception of Meridiolophus and Karagalax, has the closest affinity with Chalicotherioidea. Furthermore, the majority rule consensus tree shows that Meridiolophus is closer to Karagalax than to any other ‘isectolophid’, and both genera represent stem taxa to crown group Ceratomorpha.
The fungus Rhizoctonia solani Kuhn is a widespread and destructive plant pathogen with a very broad host range. Although various pathogens, including R. solani, have been traditionally controlled using chemical pesticides, their use faces drawbacks such as environmental pollution, development of pesticide resistance, and other negative effects. Carbendazim is a well-known antifungal agent capable of controlling a broad range of plant diseases, but its use is hampered by its poor aqueous solubility. In this study, we describe an environmentally friendly pharmaceutical microemulsion system using carbendazim as the active ingredient, chloroform and acetic acid as solvents, and the surfactants HSH and 0204 as emulsifiers. This system increased the solubility of carbendazim to 30 g/L. The optimal microemulsion formulation was determined based on a pseudo-ternary phase diagram; its physicochemical characteristics were also tested. The cloud point was greater than 90°C and it was resistant to freezing down to −18°C, both of which are improvements over the temperature range in which pure carbendazim can be used. This microemulsion meets the standard for pesticide microemulsions and demonstrated better activity against R. solani AG1-IA, relative to an aqueous solution of pure carbendazim (0.2 g/L). The mechanism of activity was reflected in the inhibition of against R. solani AG1-IA including mycelium growth, and sclerotia formation and germination were significantly better than that of 0.2 g/L carbendazim water solution according to the results of t-test done by SPSS 19.
Total syntheses of putative (±)-trichodermatides B and C are described. These efficient syntheses feature the oxa-[3 + 3] annulation strategy, leading to B and C along with their respective C2-epimers. However, these synthetic samples are spectroscopically very different from the natural products. DFT calculations of C13 chemical shifts are conducted and the predicted values are in good agreement with those of synthetic samples, thereby questioning in the accuracy of structural assignments of trichodermatides B and C.
Trichodermatides; oxa-[3 + 3] annulation; biosynthesis; Davis’ oxaziridine; electrocyclic ring-opening; DFT calculations
To discuss the feasibility and experience of treating valvular heart diseases with thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty, with domestically manufactured pipeline products for cardiopulmonary bypass.
A total of 135 patients with valvular heart disease were admitted to our hospital between January 2011 and January 2013. They received thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty, with domestically manufactured pipeline products. A cardiopulmonary bypass with domestically-manufactured pipeline products was established during the surgery. The procedure was accomplished with the assistance of thoracoscopy through a small incision in the right chest wall.
All 135 patients underwent a successful surgery, and were followed up for the duration of half a year to two years. None of them displayed any evidence of complications. Our procedure had the advantage of fewer complications and a significantly shortened time period for the patient care and hospitalization. As opposed to imported pipeline products for cardiopulmonary bypass, our procedure had the advantage of similar clinical results at a lower cost.
Thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty was proved to be a safe and effective method for cardiopulmonary bypass, with the use of domestically manufactured pipeline products.
Thoracoscopy assistance; Minimally invasive; Mitral valve surgery
Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene-nutrient interactions and the risk of non-Hodgkin lymphoma (NHL).
We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene-nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000.
A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95%CI, 0.31–0.84), the homozygous CC genotype in MBD2 (rs603097, −2176C>T) (OR = 0.37, 95%CI, 0.17–0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95%CI, 0.55–0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95%CI, 0.05–1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10-40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes.
Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through gene-nutrient interactions involving dietary nutrient intakes.
dietary nutrients; folate; one-carbon metabolizing genes; non-Hodgkin lymphoma; cancer
Intronless genes are a feature of prokaryotes; however, they are widespread and unequally distributed among eukaryotes and represent an important resource to study the evolution of gene architecture. Although many databases on exons and introns exist, there is currently no cohesive database that collects intronless genes in plants into a single database.
In this study, we present the Poaceae Intronless Genes Database (PIGD), a user-friendly web interface to explore information on intronless genes from different plants. Five Poaceae species, Sorghum bicolor, Zea mays, Setaria italica, Panicum virgatum and Brachypodium distachyon, are included in the current release of PIGD. Gene annotations and sequence data were collected and integrated from different databases. The primary focus of this study was to provide gene descriptions and gene product records. In addition, functional annotations, subcellular localization prediction and taxonomic distribution are reported. PIGD allows users to readily browse, search and download data. BLAST and comparative analyses are also provided through this online database, which is available at http://pigd.ahau.edu.cn/.
PIGD provides a solid platform for the collection, integration and analysis of intronless genes in the Poaceae. As such, this database will be useful for subsequent bio-computational analysis in comparative genomics and evolutionary studies.
Poaceae; Intronless Genes; Database
The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240–280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n = 40); (2) ischemia-reperfusion model group (I/R group: n = 40); and (3) I/R model with antagomir-320 group (I/R + antagomir-320 group: n = 40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R + antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along with the extension of the time of reperfusion. For the I/R + antagomir-320 group, the degree of myocardial fibrosis was less severe than that in the I/R group. Tissues samples in both the sham and I/R + antagomir-320 groups showed a lower apoptosis rate compared to I/R group. The qRT-PCR results indicated that miR-320 expression in the I/R group was significantly higher than that in both the sham and I/R + antagomir-320 groups. The expression level of miR-320 is significantly up-regulated in the rat model of myocardial I/R injury, and it may be implicated in the prevention of myocardial I/R injury-triggered left ventricular remodeling.
microRNA-320; myocardial ischemia-reperfusion injury; left ventricular remodeling
A 58-year-old female exhibited the onset of symmetrical sensory abnormalities of the face and extremities. The neurological examination revealed normal muscle strength with abated or absent tendon reflexes. The patient experienced symmetrical glove- and stocking-type pinprick sensations in the distal extremities and a loss of temperature sensation, but had normal proprioception and vibration senses and joint topesthesia. The lumbar puncture showed protein cell separation at the fifth week after the onset of symptoms. At the same time-point, the electrophysiological examination showed demyelination changes involving the trigeminal nerve and the somatic motor nerve. Needle electromyography revealed normal results. The clinical symptoms ceased progression at the fourth week after symptom onset, and began to improve from the sixth. This case was considered to be sensory Guillain-Barré syndrome, which was characterized by its cranial nerve involvement.
sensory Guillain-Barré syndrome; electrophysiology; cranial nerve
The objective of this study was to compare the clinical effectiveness of liraglutide with sitagliptin and assess the associated economic outcomes in patients with type 2 diabetes mellitus (T2DM) treated in real-world practice in the United States (US).
This retrospective cohort study used a large US claims database to identify patients with T2DM who initiated liraglutide or sitagliptin between January 2010 and December 2012. Adults (≥18 years old) with persistent use of therapy for ≥3 months were included. Changes in glycated hemoglobin A1c (A1C) and the proportion of patients achieving A1C targets (≤6.5% and <7%) were examined at 6-month follow-up. Diabetes-related total, medical, and pharmacy costs over the follow-up period were assessed. Multivariable regression models were used to estimate the outcomes associated with liraglutide relative to sitagliptin, adjusting for differences in patient demographics and clinical characteristics.
The study included 1,465 patients with T2DM who initiated liraglutide (N = 376) or sitagliptin (N = 1,089) (mean age [standard deviation (SD)]: 54 [8.9] vs. 58 [10.8] years; 43.9% vs. 61.8% males; both P < 0.01). After controlling for confounding factors, liraglutide patients experienced 0.31% points greater reduction in A1C (0.95% vs. 0.63% points; P < 0.01) at 6-month follow-up than sitagliptin patients and were more likely to reach A1C targets of ≤6.5% (odds ratio [OR]: 2.00; P < 0.01) and <7% (OR: 1.55; P < 0.01). Liraglutide patients had $994 lower mean diabetes-related medical costs ($1,241 vs. $2,235; P < 0.01), but $544 higher diabetes-related pharmacy costs ($2,100 vs. $1,556; P < 0.01) during the follow-up. No difference was found in the total mean diabetes-related costs between the two cohorts.
Liraglutide showed greater improvement in glycemic outcomes than sitagliptin among adult patients with T2DM in real-world clinical practice. Although diabetes-related pharmacy costs for patients using liraglutide were higher compared with sitagliptin, these were offset by significantly lower diabetes-related medical costs, resulting in similar total diabetes-related costs between the two treatment groups.
Electronic supplementary material
The online version of this article (doi:10.1007/s13300-014-0084-9) contains supplementary material, which is available to authorized users.
Clinical effectiveness; Comparative effectiveness; Costs; Glycated hemoglobin A1c (A1C); Liraglutide; Sitagliptin; Type 2 diabetes mellitus
Temperature is an important factor in affecting population dynamics and diffusion distribution of organisms. Alien species can successfully invade and colonize to various temperature environments, and one of important reasons is that alien species have a strong resistance to stress temperature. Recently, researchers have focused on the mechanisms of temperature sensing to determine the sensing and regulation mechanisms of temperature adaptation. The transient receptor potential (TRP) is one of the key components of an organism’s temperature perception system. TRP plays important roles in perceiving temperature, such as avoiding high temperature, low temperature and choosing the optimum temperature. To assess high temperature sensation and the heat resistance role of the TRP gene, we used 3′ and 5′ rapid-amplification of cDNA ends to isolate the full-length cDNA sequence of the TRP gene from Bemisia tabaci (Gennadius) MEAM1 (Middle East Asia Minor 1), examined the mRNA expression profile under various temperature conditions, and identified the heat tolerance function. This is the first study to characterize the TRP gene of invasive B. tabaci MEAM1 (MEAM1 BtTRP). The full-length cDNA of MEAM1 BtTRP was 3871 bp, and the open reading frames of BtTRP was 3501 bp, encoding 1166 amino acids. Additionally, the BtTRP mRNA expression level was significantly increased at 35°C. Furthermore, compared with control treatments, the survival rate of B. tabaci MEAM1 adults was significantly decreased under high temperature stress conditions after feeding with dsRNA BtTRP. Collectively, these results showed that MEAM1 BtTRP is a key element in sensing high temperature and plays an essential role in B. tabaci MEAM1 heat tolerance ability. Our data improved our understanding of the mechanism of temperature sensation in B. tabaci MEAM1 at the molecular level and could contribute to the understanding of the thermal biology of B. tabaci MEAM1 within the context of global climate change.
Polarimetric imaging has proved its value in medical diagnostics, bionics, remote sensing, astronomy, and in many other wide fields. Pixel-level solid monolithically integrated polarimetric imaging photo-detectors are the trend for infrared polarimetric imaging devices. For better polarimetric imaging performance the high polarization discriminating detectors are very much critical. Here we demonstrate the high infrared light polarization resolving capabilities of a quantum well (QW) detector in hybrid structure of single QW and plasmonic micro-cavity that uses QW as an active structure in the near field regime of plasmonic effect enhanced cavity, in which the photoelectric conversion in such a plasmonic micro-cavity has been realized. The detector's extinction ratio reaches 65 at the wavelength of 14.7 μm, about 6 times enhanced in such a type of pixel-level polarization long wave infrared photodetectors. The enhancement mechanism is attributed to artificial plasmonic modulation on optical propagation and distribution in the plasmonic micro-cavities.
The occurrence of intestinal polyps in people at high risk for developing colorectal cancer provides an opportunity to test the efficacy of chemoprevention agents. In this situation of treating otherwise healthy people, the potential for toxicity must be minimal. The small molecule flexible heteroarotinoid (Flex-Het), called SHetA2, has chemoprevention activity in organotypic cultures in vitro and lack of toxicity at doses capable of inhibiting xenograft tumor growth in vivo. The objective of this study was to evaluate SHetA2 chemoprevention activity and toxicity in the APCMin/+ murine model. Oral administration of SHetA2 at 30 and 60 mg/kg five days per week for 12 weeks significantly reduced development of intestinal polyps by 40 to 60% depending on the dose and sex of the treatment group. Immunohistochemical and Western blot analysis of polyps demonstrated reduced levels of cyclin D1 and proliferating cell nuclear antigen (PCNA) in both SHetA2 treatment groups. Western blot analysis also demonstrated SHetA2 induction of E-cadherin, Bax and caspase 3 cleavage along with reduction in Bcl-2, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), consistent with SHetA2 regulation of apoptosis, inflammation and angiogenesis. Neither dose caused weight loss nor gross toxicity in APCMin/+ or wild type littermates. Magnetic resonance imaging (MRI) of cardiac function showed no evidence of SHetA2 toxicity. SHetA2 did not alter left ventricular wall thickness. In summary, SHetA2 exerts chemoprevention activity without overt or cardiac toxicity in the APCMin/+ model. SHetA2 modulation of biomarkers in colon polyps identifies potential pharmacodynamic endpoints for SHetA2 clinical trials.
Chemoprevention; colon polyps; flexible heteroarotinoids; SHetA2; NSC721689
The luminal A subtype of breast cancer has a good prognosis and is sensitive to endocrine therapy but is less sensitive to chemotherapy. It is necessary to identify biomarkers to predict chemosensitivity and avoid over-treatment. We hypothesized that miRNAs in the serum might be associated with chemosensitivity.
Sixty-eight breast cancer patients received neoadjuvant chemotherapy with epirubicin plus paclitaxel. The serum of the patients was collected before chemotherapy and stored at −80°C. The samples were classified into two groups in term of the chemosensitivity. We identified the differential expression patterns of miRNAs between the chemotherapy sensitive and resistant groups using microRNA profiling. Four miRNAs that were differentially expressed between the two groups were further validated in another 56 samples. We created a model fitting formula and a receiver operating characteristics (ROC) curve using logistic regression analysis to evaluate the prediction potency.
We identified 8 miRNAs differentially expressed between the two groups: 6 miRNAs were up-regulated, and 2 miRNAs were down-regulated in the resistant group compared with the sensitive group. The expression of miR-19a and miR-205 were determined to have significant differences between the two groups (P<0.05). A predictive model of these two miRNAs was created by the logistic regression analysis. The probability of this model was 89.71%. Based on the ROC curve, the specificity was 75.00%, and the sensitivity was 81.25%.
The combination of miR-19a and miR-205 in the serum may predict the chemosensitivity of luminal A subtype of breast cancer to epirubicin plus paclitaxel neoadjuvant chemotherapy.