In order to understand and rationally construct homochiral self-assembled structures from racemic molecules, two novel crystalline metal-organic frameworks with chiral cavities were developed. The homochirality of the layers in both MOFs was achieved by forming strong coordinate bonds between the C3-symmetric cyclotriveratrylene and Zn4O(CO2)6 cluster. By changing weak π-π interactions between organic building blocks, the achiral assembly of ZnCTV-1 was successfully transformed into a chiral assembly in ZnCTV-2. This study demonstrated a possible route for designing the synthesis of chiral MOF through weak interactions.
Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage food was used as a probiotic to determine its antiviral effects on influenza virus. DK119 intranasal or oral administration conferred 100% protection against subsequent lethal infection with influenza A viruses, prevented significant weight loss, and lowered lung viral loads in a mouse model. The antiviral protective efficacy was observed in a dose and route dependent manner of DK119 administration. Mice that were treated with DK119 showed high levels of cytokines IL-12 and IFN-γ in bronchoalveolar lavage fluids, and a low degree of inflammation upon infection with influenza virus. Depletion of alveolar macrophage cells in lungs and bronchoalveolar lavages completely abrogated the DK119-mediated protection. Modulating host innate immunity of dendritic and macrophage cells, and cytokine production pattern appeared to be possible mechanisms by which DK119 exhibited antiviral effects on influenza virus infection. These results indicate that DK119 can be developed as a beneficial antiviral probiotic microorganism.
A 78-year-old male who was undergoing prolonged glucocorticoid treatment experienced cough and expectoration for 2 weeks. Galactomannan antigen analysis and a chest computed tomography (CT) scan suggested a diagnosis of invasive pulmonary aspergillosis. DNA sequencing indicated that Emericella nidulans var. echinulata was the causative agent. A combination of voriconazole and micafungin successfully treated the illness.
The results of studies that evaluated predictive factors for rebleeding in non-variceal upper gastrointestinal bleeding are inconsistent. The aim of this study was to investigate predictive factors for 30-day rebleeding in these patients. A consecutive 312 patients presenting symptoms and signs of gastrointestinal bleeding were enrolled in this prospective, observational study. Clinical and demographic characteristics and endoscopic findings were evaluated for potential factors associated with 30-day rebleeding using logistic regression analysis. Overall, 176 patients were included (male, 80.1%; mean age, 59.7±16.0 yr). Rebleeding within 7 and 30 days occurred in 21 (11.9%) and 27 (15.3%) patients, respectively. We found that chronic kidney disease (CKD) (OR, 10.29; 95% CI, 2.84-37.33; P<0.001), tachycardia (pulse>100 beats/min) during the admission (OR, 3.79; 95% CI, 1.25-11.49; P=0.019), and Forrest classes I, IIa, and IIb (OR, 6.14; 95% CI, 1.36-27.66; P=0.018) were significant independent predictive factors for 30-day rebleeding. However, neither Rockall nor Blatchford scores showed statistically significant relationships with 30-day rebleeding in a multivariate analysis. CKD, hemodynamic instability during hospitalization, and an endoscopic high-risk appearance are significantly independent predictors of 30-day rebleeding in patients with non-variceal upper gastrointestinal bleeding. These factors may be useful for clinical management of such patients.
Nonvariceal Upper Gastrointestinal Bleeding; Rebleeding; Kidney Failure, Chronic; Predictive Factors
Targeted therapy is becoming an increasingly important component in the treatment of cancer. How to accurately monitor targeted therapy has been crucial in clinical practice. The traditional approach to monitor treatment through imaging has relied on assessing the change of tumor size by refined World Health Organization criteria, or more recently, by the Response Evaluation Criteria in Solid Tumors. However, these criteria, which are based on the change of tumor size, show some limitations for evaluating targeted therapy. Currently, genetic alterations are identified with prognostic as well as predictive potential concerning the use of molecularly targeted drugs. Conversely, considering the limitations of invasiveness and the issue of expression heterogeneity, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively, and has been a particularly attractive tool for monitoring treatment in clinical cancer practice. This review focuses on the applications of different kinds of molecular imaging including positron emission tomography-, magnetic resonance imaging-, ultrasonography-, and computed tomography-based imaging strategies on monitoring targeted therapy. In addition, the key challenges of molecular imaging are addressed to successfully translate these promising techniques in the future.
molecular imaging; targeted therapy; PET; MRI; US; CT
Oral polio vaccine (OPV) can mutate and cause outbreaks of paralytic poliomyelitis with prolonged replication. After poliovirus eradication, global use of inactivated polio vaccine (IPV) may be needed until all OPV stops circulating. Mexico, where children receive routine IPV but where OPV is given only during biannual national immunization weeks (NIWs), provides a natural setting to study duration of OPV circulation in a community primarily vaccinated with IPV.
One-liter sewage samples from four separate arroyos (creeks) near Orizaba, Mexico, were collected monthly for 12 months. Concentrated sewage underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3 and their variants containing the serotype-specific point mutation in the 5′ untranslated region associated with neurovirulence.
OPV was detected 3, 4, 5, and 7 months after the May 2010 NIW, but was not detected at 6 or 8 months. A second and third NIW occurred in February 2011 and May 2011, and OPV was detected in the sewage monthly after both of these NIW through July 2011 when collection stopped. The OPV detected was primarily serotype 2 and predominantly contained the point mutations in the 5′ untranslated region associated with increased neurovirulence.
OPV was detected in sewage as late as 7 months after an NIW in a Mexican community primarily vaccinated with IPV, but was not detected at 8 months, suggesting that OPV circulation may have ceased. These data suggest that in communities with high vaccination rates, 1 or 2 years of IPV administration after OPV cessation could be sufficient to prevent outbreaks of paralytic poliomyelitis from vaccine-derived strains.
Polio; OPV; Mexico; Sewage; PCR
Toll-like receptors (TLRs), as major innate immune mediators, may be involved in clearance of cerebral amyloid-β (Aβ) deposits. Recently, a novel TLR9 signaling pathway has been uncovered, which is functionally associated with the immune inflammatory response and reducing Aβ burden in Alzheimer’s disease (AD) mice. Therefore, TLR9 might represent a reasonable functional candidate gene for AD.
Our study investigated 1,133 sporadic late-onset AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han Chinese population. One selected functional rs187084 polymorphism within the TLR9 gene was genotyped by polymerase chain reaction-ligase detection reaction in a case–control associated study. The TLR9 rs187084 variant homozygote GG was significantly associated with a decreased LOAD risk after adjusting for age, gender, and ApoE ϵ4 status by logistic regression analysis (P = 0.035). Our result showed significant evidence of the interaction of ApoE ϵ4 with rs187084. When we further stratified our data by the ApoE ϵ4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ϵ4 carriers (P < 0.001, P = 0.003, respectively). Moreover, we examined TLR9 expression in peripheral blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084 polymorphism was associated with a higher TLR9 expression than two other genotypes in LOAD patients.
Our findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.
Alzheimer’s disease; Polymorphisms; TLR9; rs187084; Expression; Association study
Human DNA polymerase iota (pol ι) possesses high error-prone DNA replication features and performs translesion DNA synthesis. It may be specialized and strictly regulated in normal mammalian cells. Dysregulation of pol ι may contribute to the acquisition of a mutator phenotype. However, there are few reports describing the transcription regulatory mechanism of pol ι, and there is controversy regarding its role in carcinogenesis. In this study, we performed the deletion and point-mutation experiment, EMSA, ChIP, RNA interference and western blot assay to prove that c-Jun activated by c-Jun N-terminal kinase (JNK) regulates the transcription of pol ι in normal and cancer cells. Xeroderma pigmentosum group C protein (XPC) and ataxia-telangiectasia mutated related protein (ATR) promote early JNK activation in response to DNA damage and consequently enhance the expression of pol ι, indicating that the novel role of JNK signal pathway is involved in DNA damage response. Furthermore, associated with elevated c-Jun activity, the overexpression of pol ι is positively correlated with the clinical tumor grade in 97 bladder cancer samples and may contribute to the hypermutagenesis. The overexpressed pol ι-involved mutagenesis is dependent on JNK/c-Jun pathway in bladder cancer cells identifying by the special mutation spectra. Our results support the conclusion that dysregulation of pol ι by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol ι or c-Jun in mutagenesis.
The MYB proteins comprise one of the largest families of transcription factors (TFs) in plants. Although several MYB genes have been characterized to play roles in secondary metabolism, the MYB family has not yet been identified in apple. In this study, 229 apple MYB genes were identified through a genome-wide analysis and divided into 45 subgroups. A computational analysis was conducted using the apple genomic database to yield a complete overview of the MYB family, including the intron-exon organizations, the sequence features of the MYB DNA-binding domains, the carboxy-terminal motifs, and the chromosomal locations. Subsequently, the expression of 18 MYB genes, including 12 were chosen from stress-related subgroups, while another 6 ones from other subgroups, in response to various abiotic stresses was examined. It was found that several of these MYB genes, particularly MdoMYB121, were induced by multiple stresses. The MdoMYB121 was then further functionally characterized. Its predicted protein was found to be localized in the nucleus. A transgenic analysis indicated that the overexpression of the MdoMYB121 gene remarkably enhanced the tolerance to high salinity, drought, and cold stresses in transgenic tomato and apple plants. Our results indicate that the MYB genes are highly conserved in plant species and that MdoMYB121 can be used as a target gene in genetic engineering approaches to improve the tolerance of plants to multiple abiotic stresses.
This study was performed to determine the accuracy of proton magnetic spectroscopy (1H-MRS) lipid peak as a noninvasive tool for quantitative in vivo detection of brain cell death. Seven day-old Sprague Dawley rats were subjected to 8% oxygen following a unilateral carotid artery ligation. For treatment, cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was measured using 1H-MRS at 24 hr after HI, and then brains were harvested for fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent probe JC-1, and for adenosine-5'-triphosphate (ATP) and lactate. Increased lipid peak at 1.3 ppm measured with 1H-MRS, apoptotic and necrotic cells, and loss of mitochondrial membrane potential (ΔΨ) at 24 hr after HI were significantly improved with cycloheximide treatment. Significantly reduced brain ATP and increased lactate levels observed at 24 hr after HI showed a tendency to improve without statistical significance with cycloheximide treatment. Lipid peak at 1.3 ppm showed significant positive correlation with both apoptotic and necrotic cells and loss of ΔΨ, and negative correlation with normal live cells. Lipid peak at 1.3 ppm measured by 1H-MRS might be a sensitive and reliable diagnostic tool for quantitative in vivo detection of brain cell death after HI.
Hypoxia-Ischemia, Brain; Animals; Newborn; Magnetic Resonance Spectroscopy; Flow Cytometry
Controlling positional selectivity of C–H activation in molecules possessing multiple inequivalent C–H bonds is one of the most important challenges in developing synthetically useful C–H activation reactions. One widely used approach utilizes σ-chelating directing groups to achieve ortho-selectivity through conformational rigid five- or six-membered cyclic pre-transition states (TS).1–14 We envisioned that an “end-on” chelating template capable of delivering catalysts to previously inaccessible remote meta-C–H bonds via a macrocyclic cyclophane-like pre-TS could overcome the limitations imposed by traditional ortho-directing groups. Herein, we report a class of readily removable nitrile-containing templates that direct the activation of distal meta-C–H bonds (≥ 10 bonds away) of a tethered arene. We attribute this new mode of C–H activation to the weak “end-on” coordination of the linear nitrile group to metal center, as previously observed by Schwarz in the study of remote C–H activation of alkyl nitriles in gas phase.15, 16 The coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta-C–H activation event. Remarkably, this template overrides electronic and steric biases and ortho-directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids), thus constituting a fundamentally new mode of directed C–H activation that is anticipated to be widely adopted.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.
Reactions that convert carbon–hydrogen (C–H) bonds into carbon–carbon (C–C) or carbon–heteroatom (C–Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C–H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C–H functionalization reactions become more widely utilized in organic synthesis.
Research in the area of homogeneous transition metal–catalyzed C–H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as “first functionalization.” Here the substrates are nonpolar and hydrophobic and thus interact very weakly with polar metal species. To overcome this weak affinity and drive metal-mediated C–H cleavage, chemists often use hydrocarbon substrates in large excess (for example, as solvent). Because highly reactive metal species are needed in first functionalization, controlling the chemoselectivity to avoid over-functionalization is often difficult. Additionally, because both substrates and products are comparatively low-value chemicals, developing cost-effective catalysts with exceptionally high turnover numbers that are competitive with alternatives (including heterogeneous catalysts) is challenging. Although an exciting field, first functionalization is beyond the scope of this Account.
The second subfield of C–H functionalization involves substrates containing one or more pre-existing functional groups, termed “further functionalization.” One advantage of this approach is that the existing functional group (or groups) can be used to chelate the metal catalyst and position it for selective C–H cleavage. Precoordination can overcome the paraffin nature of C–H bonds by increasing the effective concentration of the substrate so that it needn't be used as solvent. From a synthetic perspective, it is desirable to use a functional group that is an intrinsic part of the substrate so that extra steps for installation and removal of an external directing group can be avoided. In this way, dramatic increases in molecular complexity can be accomplished in a single stroke through stereo- and site-selective introduction of a new functional group. Although reactivity is a major challenge (as with first functionalization), the philosophy in further functionalization differs—the major challenge is developing reactions that work with predictable selectivity in intricately functionalized contexts on commonly occurring structural motifs.
In this Account, we focus on an emergent theme within the further functionalization literature: the use of commonly occurring functional groups to direct C–H cleavage through weak coordinations. We discuss our motivation for studying Pd-catalyzed C–H functionalization assisted by weakly coordinating functional groups and chronicle our endeavors to bring reactions of this type to fruition. Through this approach, we have developed reactions with a diverse range of substrates and coupling partners, with the broad scope likely stemming from higher reactivity of the less stable cyclopalladated intermediates held in place by weak coordinations.
B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with IC50 values of 29.2 and 20.7 µM, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated q2 values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.
Arylpropanol; Ceramide; Cytotoxicity; QSAR
AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China.
METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenoscopy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed.
RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89, 23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932).
CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.
Missed diagnosis; Early gastric cancer; High-grade intraepithelial neoplasia; Endoscopic diagnosis; Biopsies
Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen-sensing pathway that regulates the ERYTHROPOIETIN (EPO) gene. More specifically, recent studies have identified erythrocytosis-associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor-2α (HIF-2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T and F540L, both associated with erythrocytosis. Met-535 has previously been identified as a residue mutated in other patients with erythrocytosis, although the mutation of this particular residue to Thr has not been reported. In contrast, Phe-540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF-2α with both VHL and PHD2.
erythropoietin; erythrocytosis; Hypoxia Inducible Factor-2α; oxygen-sensing; prolyl hydroxylation
The aim of this study was to investigate risk factors of suicide ideation in general population. A total of 1,116 adults were sampled with randomization in an urban area. After excluding 116 participants due to incomplete answer, 1,000 participants (500 males; mean age 39.6 ± 11.6) completed self-report questionnaire including the Center for Epidemiologic Study Depression Scale (CES-D), the Beck Scale for Suicide Ideation (BSI), the Spielberger State-Trait Anger Expression Inventory (STAXI), the Barratt Impulsiveness Scale (BIS), and questions on weekday sleep duration. Results showed higher scores on the BSI were related with higher scores on the STAXI, CES-D, a family history of psychiatric illness, and short or long sleep duration (≤ 5 or ≥ 10 hr) (adjusted R2 = 0.151, P < 0.001, P < 0.001, P = 0.001, and P = 0.008, respectively). The predictive power of the STAXI scores, the presence of psychiatric family history and short or long sleep duration was stronger in the high CES-D group with scores of 16 or higher (adjusted R2 = 0.275, P < 0.001, P < 0.001, and P < 0.001, respectively). These findings suggest that suicide idea in general population may be related with the presence of family history for psychiatric illness, depressive mood, high anger and short or long sleep duration.
General Population; Risk Factor; Suicide Idea
Malacoplakia is a chronic inflammatory disease. The disease mainly affects the urinary bladder, although involvement of extravesical sites is increasingly being documented. Most frequently involved is the urinary tract, particularly the urinary bladder, although the testis, epididymis, lungs, bone, colon, prostate, female genital organs, and retroperitoneum can also be involved. Here we report the case of a 61-year-old man with a scrotal mass with histology that was specific for malacoplakia of the epididymis. The histologic workup demonstrated extensive involvement of the epididymis by diffuse infiltrates of large histiocytes with eosinophilic granular cytoplasm and numerous Michaelis-Gutmann bodies, which were diagnostic of malakoplakia. This is the first case of epididymal malacoplakia in our country and the first case of epididymal malacoplakia without concurrent involvement of the testis. There have been few reports of this condition worldwide.
MicroRNAs (miRNAs) are a class of recently discovered non-coding small RNA molecules, on average approximately 21 nucleotides in length, which underlie numerous important biological roles in gene regulation in various organisms. The miRNA database (release 18) has 18,226 miRNAs, which have been deposited from different species. Although miRNAs have been identified and validated in many plant species, no studies have been reported on discovering miRNAs in Panax ginseng Meyer, which is a traditionally known medicinal plant in oriental medicine, also known as Korean ginseng. It has triterpene ginseng saponins called ginsenosides, which are responsible for its various pharmacological activities. Predicting conserved miRNAs by homology-based analysis with available expressed sequence tag (EST) sequences can be powerful, if the species lacks whole genome sequence information. In this study by using the EST based computational approach, 69 conserved miRNAs belonging to 44 miRNA families were identified in Korean ginseng. The digital gene expression patterns of predicted conserved miRNAs were analyzed by deep sequencing using small RNA sequences of flower buds, leaves, and lateral roots. We have found that many of the identified miRNAs showed tissue specific expressions. Using the insilico method, 346 potential targets were identified for the predicted 69 conserved miRNAs by searching the ginseng EST database, and the predicted targets were mainly involved in secondary metabolic processes, responses to biotic and abiotic stress, and transcription regulator activities, as well as a variety of other metabolic processes.
Panax ginseng; MicroRNA; Expressed sequence tag; Deep sequencing
Transfusion therapy is currently an effective therapeutic intervention in a number of diseases, including sickle cell disease. However, its use is complicated by a high incidence of red blood cell (RBC) alloimmunization in the transfusion recipients. The identification of T regulatory cells (Tregs) among the CD4+CD25+ T cell subset as key regulators of peripheral tolerance in mice as well as humans has opened an exciting era in the prevention and treatment of autoimmune disease and for improving organ transplantation. However, their potential in inducing transfusion tolerance remains to be explored. We used red cells from mice transgenic for human glycophorin A blood group antigen as donor cells and transfused wild-type mice to induce alloantibodies, as an experimental system to study RBC alloimmunization. We found that depletion with anti-CD25 enhanced the alloantibody production, indicating that CD25 Tregs play an important role in regulation of alloantibody responses. More importantly, adoptive transfer of purified population of CD4+CD25+ but not CD4+CD25– cells from naïve mice prevented the induction of IgG and IgM alloantibody production in transfusion recipients, with a concomitant reduction in activated splenic B cells and macrophages. Similarly, adoptive transfer of purified populations of CD4+CD25+ cells from naïve mice into naïve syngeneic recipients inhibited the anti-Ig response to rat RBCs in the recipients but transfer of control CD4+CD25– cells did not. Altogether, our results demonstrate that Tregs participate in the control of trans-fusion-associated RBC alloantibody responses, opening up the possibility that Treg immunotherapy may be exploited for suppressing transfusion immunization events.
The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation. Here we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6 hours after ischemic injury. Finally, the protective effects of IA were partially mediated by the TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage.
Cerebral ischemia; inflammation; NF-κB; neuroprotection; incensole acetate; Boswellia
Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.
Materials and Methods
The current study was conducted in 136 Korean pregnant women, who gave birth at Gil Hospital, from October 2008 to May 2011. These study subjects included 95 subjects with GDM and 41 non-diabetic controls. We selected the specific genes of PPARγ2, IGF2BP2, and KCNQ1 for study and amplified them using the polymerase chain reaction. This was followed by genotyping for single nucleotide polymorphisms. We then compared the genotype frequencies between patients with GDM and non-diabetic controls using the χ2 test. We obtained and analyzed clinical information using Student's t-test, and statistical analyses were conducted using logistic regression with SPSS Statistics software, version 19.0.
Significant differences were observed in maternal age, body mass index, weight gain and weight at time of delivery between the groups compared. Among pregnant women, polymorphisms in PPARγ2 and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms.
Our results indicated that genetic polymorphisms could also be of value in predicting the occurrence and diagnosis of GDM.
Gestational diabetes mellitus; type 2 diabetes mellitus; gene; single nucleotide polymorphism
Attributional style, especially external personal attribution bias, was found to play a pivotal role in clinical and non-clinical paranoia. The study of the relationship of the tendency to infer/perceive hostility and blame with theory of mind skills has significant theoretical importance as it may provide additional information on how persons process social situations. The aim of this study was whether hostility perception bias and blame bias might be associated with theory of mind skills, neurocognition and emotional factors in healthy persons.
Total 263 participants (133 male and 130 female) were recruited. The attributional style was measured by using the Ambiguous Intentions Hostility Questionnaire (AIHQ). Participants were requested to complete a Brüne's Theory of Mind Picture Stories task, neurocognitive task including Standard Progressive Matrices (SPM) and digit span, and other emotional dysregulation trait scales including Rosenberg's self-esteem, Spielberg's trait anxiety inventory, and Novaco anger scale.
Multiple regression analysis showed that hostility perception bias score in ambiguous situation were found to be associated with theory of mind questionnaire score and emotional dysregulation traits of Novaco anger scale. Also, composite blame bias score in ambiguous situation were found to be associated with emotional dysregulation traits of Novaco anger scale and Spielberg's trait anxiety scale.
The main finding was that the attributional style of hostility perception bias might be primarily contributed by theory of mind skills rather than neurocognitive function such as attention and working memory, and reasoning ability. The interpretations and implications would be discussed in details.
Attributional style; Theory of Mind skills; Healthy persons
Antral web is a rare cause of gastric outlet obstruction in neonate. It is a 2-4 mm thin mucous membrane that can be found anywhere from 1 to 7 cm proximal to the pylorus. The baby was born at gestational age of 32+1 weeks with 1,880 g as 2nd baby of dizygotic twin. After birth, the baby had constant non-bilious vomiting without feeding while he didn't show abdominal distension or discoloration. The infantogram showed distended stomach with distal small bowel gas. Upper gastrointestinal series revealed that the antrum was abruptly narrowed at 1 cm proximal to pylorus. We performed laparotomy at the 10th day after birth and excised the 2 mm-thick web circumferentially. He began milk feeding after 6 days and discharged uneventfully at postoperative 35 days with corrected age of 38+4 weeks with body weight 2,420 g. The antral web should be considered in the case of non-bilious vomiting in neonate.
Gastric outlet obstruction; Antrum; Web; Vomiting
Self-reactive natural antibodies initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the post-ischemic brain, and the role of natural antibodies in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in antibody deficient Rag1−/− mice after 60 minutes of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1−/− mice restored injury to that seen in wild-type mice, as demonstrated by infarct volume, demyelination and neurological scoring. IgM deposition was demonstrated in both wild-type mice and reconstituted Rag1−/− mice, and IgM co-localized with the complement activation fragment, C3d, following B4 mAb reconstitution. Further, recombinant annexin IV significantly reduced infarct volumes in wild-type mice and in Rag1−/− mice administered normal mouse serum, demonstrating that a single antibody reactivity is sufficient to develop cerebral ischemia reperfusion injury in the context of an entire natural antibody repertoire. Finally, C2 and B4 mAbs bound to hypoxic, but not normoxic, human endothelial cells in vitro. Thus, the binding of pathogenic natural IgM to post-ischemic neoepitopes initiates complement-dependent injury following murine cerebral ischemia and reperfusion and, based also on previous data investigating IgM reactivity in human serum, there appears to be a similar recognition system in both mouse and man.