Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

Background:

Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae, a traditional herbal medicine that has been used clinically for the treatment of cardiovascular diseases. This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α (TNF-α)-activated human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki disease.

Methods:

HCAECs were pretreated with 1–10 μmol/L of Sal B, and then stimulated by TNF-α at different time points. The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay, respectively. Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence, electrophoretic mobility shift assay, and Western blot assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38) were determined by Western blot assay.

Results:

After HCAECs were exposed to TNF-α, 1–10 μmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity. Furthermore, Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min. In addition, Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.

Conclusions:

The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB, JNK, and ERK1/2 signaling pathways.     

Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin

Background:

Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA.

Methods:

We divided 32 4-week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region.

Results:

Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3β activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH.

Conclusions:

Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt/β-catenin signaling pathway.     

Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

Background:

Previous studies have indicated that the cognitive deficits in patients with Alzheimer''s disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

Methods:

Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and “small-world” property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz, and 0.11–0.25 Hz).

Results:

At lower-frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz), the global efficiency, the CC and the “small-world” properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11–0.25 Hz), the CpL was much longer, and the “small-world” property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

Conclusions:

This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.     

Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report

Background:

Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS.

Methods:

Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human β-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1–10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-κB (NF-κB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests.

Results:

The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ± 0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group.

Conclusions:

Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process of pCRS.     

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice

Background:

Early diagnosis assumes a vital role in an effective treatment of Alzheimer''s disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.

Methods:

A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(¹⁸ F) fluoro-D-glucose ([¹⁸ F]-FDG) uptake in the hippocampus and cerebral cortex.

Results:

With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (¹⁸ F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (¹⁸ F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.

Conclusions:

The decline of (¹⁸ F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.     

Effect of Hyperbaric Oxygen on the Growth of Intracranial Glioma in Rats

Background:

Numerous studies have confirmed that hyperbaric oxygen (HBO) in combination with radiotherapy or chemotherapy may increase the efficacy of radiotherapy or chemotherapy in patients with glioma. However, whether HBO therapy alone may inhibit or promote the growth of malignant tumors remains controversial. This study aimed to investigate the effect of HBO on the growth of glioma in rats, and the impact of HBO on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α), angiogenesis, and apoptosis of glioma cells.

Methods:

Male Sprague–Dawley rats were treated with or without HBO after glioma cell inoculation and followed for up to 16 days postinoculation. Rats were randomized to receive bilateral forelimb function tests (n = 20 per group) and head magnetic resonance imaging (n = 5 per group). Differences between HBO and control groups were tested using 2-sample independent t-tests and changes over time within treatment groups were analyzed using a repeated measurement analysis of variance with Bonferroni correction. The effect of HBO on the expression of VEGF, HIF-1α, von Willebrand factor, angiogenesis, and tumor cell apoptosis were also examined (n = 5 per group).

Results:

Forelimb function scores were reduced in both HBO-treated and control groups. HBO-treated rats had significantly larger tumor volume and more water in the cerebellum compared with control rats. The intratumoral expression of VEGF was significantly higher in HBO-treated rats compared with control rats (23.2% vs. 13.3%, P = 0.002). HIF-1α was significantly increased in HBO-treated rats compared with controls in the expression of both intratumoral (72.7% vs. 54.9%, P = 0.001) and peritumoral (2.6% vs. 1.9%, P = 0.003) cells. The intratumoral microvessel density (MVD) was significantly higher in the HBO group (15.6 vessels/field vs. 4.4 vessels/field, P < 0.001), and the peritumoral MVD was not significantly different between the two groups (P > 0.05). Apoptosis was significantly lower in HBO-treated rats compared with controls (44.4% vs. 82.8% for intratumoral; 10.1% vs. 77.5% for peritumoral, both P < 0.001).

Conclusions:

The current results demonstrate that HBO alone may promote tumor growth, and is therefore not suitable to treat patients with gliomas with neurological deficits or disorders with HBO alone. If HBO must be used as a mean of rehabilitation, it is recommended that HBO should be combined with radiotherapy or chemotherapy.     

Frequency of cognitive impairment and depression in Parkinson's disease: A preliminary case-control study

Background:

This study aimed to determine the frequency of cognitive impairment and depression in our Parkinson''s Disease (PD) and their relationship with disease severity and disability.

Patients and Methods:

A total of 40 PD patients and 40 age-, sex-, and educationally matched controls were studied. The Unified Parkinson Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores and the Hoehn and Yahr (HY) stage were documented. Depression was assessed using the Zung Self-Rating Depression Scale (ZSDS), while cognition was evaluated using a composite score of the mini-mental state examination (MMSE) score and category fluency score.

Results:

A total of 55% (22/40) of PD and 10% (4 of 40) of controls had depression (P<0.001). A total of 60% of PD (24/40) and 5% of controls (2/40) had cognitive impairment (P<0.001). Both NMS coexisted in 16 of 40 PD (40%) compared with none of the controls (P<0.001). UPDRS (motor and ADL) scores and HY stage were significantly worse with impaired ZSDS scores - P 0.001. UPDRS ADL was significantly impaired by the presence of cognitive impairment. Coexisting depression and cognitive impairment were associated with significant worsening of all scores of severity and disability.

Conclusion:

Cognitive impairment and depression accompany our PD and are related to disability and worsening disease severity.     

Staging of colorectal cancer using contrast-enhanced multidetector computed tomographic colonography

INTRODUCTION

Preoperative staging is essential for the optimal treatment and surgical planning of colorectal cancers. This study was aimed to evaluate the accuracy of colorectal cancer staging done using contrast-enhanced multidetector computed tomographic colonography (CEMDCTC).

METHODS

We recruited 25 patients with 28 proven colorectal cancers. A 16-slice multidetector computed tomography scanner was used to generate two-dimensional multiplanar reformatted sagittal, coronal and oblique coronal images, and three-dimensional virtual colonography (endoluminal) images. Axial and reformatted views were analysed, and TNM staging was done. Patients underwent surgery and conventional colonoscopy, and surgical histopathological correlation was obtained.

RESULTS

The diagnostic accuracies for TNM colorectal cancer staging were 92.3% for T staging, 42.3% for N staging and 96.1% for M staging using CEMDCTC. There was excellent positive correlation for T staging between CEMDCTC and both surgery (κ-value = 0.686) and histopathology (κ-value = 0.838) (p < 0.0001), and moderate positive correlation for N staging between CEMDCTC and surgery (κ-value = 0.424; p < 0.0001). The correlation between CEMDCTC and histopathology for N staging was poor (κ-value = 0.186; p < 0.05); the negative predictive value was 100% for lymph node detection. Moderate positive correlation was seen for M staging between CEMDCTC and both surgery (κ-value = 0.462) and histopathology (κ-value = 0.649). No false negatives were identified in any of the M0 cases.

CONCLUSION

CEMDCTC correlated well with pathologic T and M stages, but poorly with pathologic N stage. It is an extremely accurate tool for T staging, but cannot reliably distinguish between malignant lymph nodes and enlarged reactive lymph nodes.     

Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia

Background

Knowledge of the oncogenic signaling pathways of T-cell acute lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation of the nuclear factor kappa B (NF-κB) signaling pathway has been detected in various lymphoid malignancies and plays a key role in the development of these carcinomas. The zinc finger-containing protein, A20, is a central regulator of multiple NF-κB-activating signaling cascades. A20 is frequently inactivated by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However, few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of interest to analyze the expression characteristics of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1.

Methods

The expression levels of CARMA1, BCL10, MALT1, A20, and NF-κB were detected in peripheral blood mononuclear cells (PBMCs) from 21 patients with newly diagnosed T-ALL using real-time PCR, and correlations between the aberrant expression of these genes in T-ALL was analyzed. Sixteen healthy individuals, including 10 males and 6 females, served as controls.

Results

Significantly lower A20 expression was found in T-ALL patients (median: 4.853) compared with healthy individuals (median: 8.748; P = 0.017), and significantly increased expression levels of CARMA1 (median: 2.916; P = 0.034), BCL10 (median: 0.285; P = 0.033), and MALT1 (median: 1.201; P = 0.010) were found in T-ALL compared with the healthy individuals (median: 1.379, 0.169, and 0.677, respectively). In contrast, overexpression of NF-κB (median: 0.714) was found in T-ALL compared with healthy individuals (median: 0.335; P = 0.001). A negative correlation between the MALT1 and A20 expression levels and a positive correlation between CARMA1 and BCL10 were found in T-ALL and healthy individuals. However, no negative correlation was found between A20 and NF-κB and the MALT1 and NF-κB expression level in the T-ALL group.

Conclusions

We characterized the expression of the CARMA-BCL10-MALT1-A20-NF-κB pathway genes in T-ALL. Overexpression of CARMA-BCL10-MALT in T-ALL may contribute to the constitutive cleavage and inactivation of A20, which enhances NF-κB signaling and may be related to T-ALL pathogenesis.     

P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

Background:

The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves.

Methods:

Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.

Results:

The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits.

Conclusions:

The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.     

Activation of γ-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats

Background:

Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABA_AR). Whether GABA_AR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study.

Methods:

According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca²⁺]i) was measured by Fura-2-acetoxymethyl ester; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory.

Results:

The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca²⁺]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca²⁺]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups.

Conclusions:

Activation of GABA_A R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.     

Amide Proton Transfer Magnetic Resonance Imaging of Alzheimer's Disease at 3.0 Tesla: A Preliminary Study

Background:

Amide proton transfer (APT) imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging (MRI) in the field of molecular and cellular imaging. The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer''s disease (AD) at 3.0 Tesla.

Methods:

Twenty AD patients (9 men and 11 women; age range, 67–83 years) and 20 age-matched normal controls (11 men and 9 women; age range, 63–82 years) underwent APT and traditional MRI examination on a 3.0 Tesla MRI system. The magnetic resonance ratio asymmetry (MTR_asym) values at 3.5 ppm of bilateral hippocampi (Hc), temporal white matter regions, occipital white matter regions, and cerebral peduncles were measured on oblique axial APT images. MTR_asym (3.5 ppm) values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test. Controlling for age, partial correlation analysis was used to investigate the associations between mini-mental state examination (MMSE) and the various MRI measures among AD patients.

Results:

Compared with normal controls, MTR_asym (3.5 ppm) values of bilateral Hc were significantly increased in AD patients (right 1.24% ± 0.21% vs. 0.83% ± 0.19%, left 1.18% ± 0.18% vs. 0.80%± 0.17%, t = 3.039, 3.328, P = 0.004, 0.002, respectively). MTR_asym (3.5 ppm) values of bilateral Hc were significantly negatively correlated with MMSE (right r = −0.559, P = 0.013; left r = −0.461, P = 0.047).

Conclusions:

Increased MTR_asym (3.5 ppm) values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.     

Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction

Background:

Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro.

Methods:

Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.

Results:

Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.

Conclusion:

These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.     

Retarded hippocampal development following prenatal exposure to ethanolic leaves extract of Datura metel in wistar rats

Background:

Datura metel contains atropine alkaloids and has been used to treat complication like asthma and, bronchitis, because of its anticholinergic properties.

Aim:

This study aimed to determine the prenatal effects of ethanolic extract of D. metel leaves exposure on the development of hippocampus.

Materials and Methods:

Twenty rats (12 females and 8 males) were purchased. The females were grouped into four groups (A_D). Group A were given 500 mg/kg body weight of the extract on the first day of fertilization to the end of gestation period, Group B were given 500 mg/kg body weight on the 8^th day of fertilization to the end of gestation period, Group C were given 500 mg/kg body weight on 15^th day of fertilization to the end of gestation period and Group D were given normal saline throughout the gestation period.

Results:

Rats in Group A showed no implantation, rats in Group B had abortion on the 7^th day after administration, and rats in Group C gave birth with their litters showing retarded hippocampus development and neural degeneration and rats in Group D (control) showed normal development.

Conclusion:

Ethanolic extract of D. metel leaf is teratogenic in the late stage of pregnancy, is abortificient and can serve as a contraceptive.     

Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

Objective:

To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).

Data Sources:

We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: “inflammatory bowel disease (IBD)” OR “Crohn''s disease” OR “ulcerative colitis” AND (“vaccination” OR “vaccine”) AND (“corticosteroids” OR “mercaptopurine” OR “azathioprine” OR “methotrexate [MTX]”) AND “immunomodulators.”

Study Selection:

The inclusion criteria of articles were that the studies: (1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents). The exclusion criteria of articles were that the studies: (1) History of hepatitis B virus (HBV), influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.

Results:

Patients treated with immunomodulators were associated with lower response rates to vaccination.

Conclusions:

Immunomodulators may impair the immune response to vaccination in patients with IBD. Vaccination should be made at the time of diagnosis or before starting immunosuppressed therapy.     

Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats

Background and Aims

Butyrate enemas have been shown to be effective in treatment of ulcerative colitis, but the mechanism of the effects of butyrate is not totally known. This study evaluates effects of topical treatment of sodium butyrate (NaB) and 5‐aminosalicylic acid (5‐ASA) on the expression of trefoil factor 3 (TFF3), interleukin 1β (IL1β), and nuclear factor κB (NFκB) in trinitrobenzene sulphonic acid (TNBS) induced colitis in rats.

Methods

Distal colitis was induced in male Wistar rats by colonic administration of TNBS and colonically treated with NaB, 5‐ASA, combination of NaB and 5‐ASA, and normal saline for 14 consecutive days. Colonic damage score, tissue myeloperoxidase (MPO) activity, TFF3 mRNA expression, serum IL1β production, and tissue NFκB expression were determined, respectively.

Results

Treatment of NaB, 5‐ASA, and the combination improved diarrhoea, colonic damage score, and MPO activities, increased TFF3 mRNA expression, and decreased serum IL1β production and tissue NFκB expression. The combination therapy of NaB and 5‐ASA had better effects than any other single treatment.

Conclusions

The combination of topical treatment of NaB and 5‐ASA was effective for relieving and repairing colonic inflammation and the effects were related to stimulation of TFF3 mRNA expression and down‐regulation of IL1β production and NFκB expression.