Enhancement of Immune Responses by Co-delivery of CCL19/MIP-3beta Chemokine Plasmid With HCV Core DNA/Protein Immunization

Background:

Using molecular adjuvants offers an attractive strategy to augment DNA vaccine-mediated immune responses. Several studies have revealed that an efficient HCV vaccine model should be able to induce both humoral and cell mediated immune responses targeting the conserved regions of the virus to circumvent the immune escape mutants. The beta chemokine Macrophage Inflammatory Protein 3-beta (MIP-3beta) is a key modulator of dendritic cells (DCs) and T-cells interaction, functions during immune response induction and is secreted specifically by cells in the lymphoid tissues.

Objectives:

In the present study, we questioned whether co-administration of MIP-3beta gene could enhance the immune responses to HCV core in DNA vaccination.

Materials and Methods:

Expression and biological activity of MIP-3beta expressing plasmid were evaluated by ELISA and transwell migration assays, respectively. HCV core DNA vaccine ± plasmid expressing MIP-3beta were electroporated subcutaneously to the front foot pads of BALB/c mice on days 0 and 14, and HCV core protein booster was applied to all core-DNA-vaccine received mice on the day 28. Both cell mediated immunity (proliferation, IFN-γ and IL-4 cytokine release, IFN-γ ELISpot and cytotoxic Granzyme B release assays) and humoral immune responses (total IgG and IgG2a/IgG1 subtyping) were evaluated ten days after final immunization.

Results:

Mice covaccinated with MIP-3beta elicited an enhanced Th1 biased systemic immune response as evidenced by higher IFN-γ/IL-4 and anti-core IgG2a/IgG1 ratio, lymphoproliferation, strong cytolytic GrzB release and enhanced population of IFN-γ producing immunocytes. Likewise, the humoral immune response assumed as the total anti-core IgG level was augmented by MIP-3beta co-delivery.

Conclusions:

These results exhibited the immuno potentiator effects of MIP-3beta plasmid when coadministrated with the HCV core DNA vaccine. Complimentary studies integrating MIP-3beta as a genetic adjuvant in HCV-core-DNA vaccination models are warranted.     

Partial Internal Biliary Diversion in Progressive Familial Intrahepatic Cholestasis: Introduction of a New Approach

Introduction:

Facilitation of biliary salts secretion represents the mainstay of treatment for progressive familial intrahepatic cholestasis (PFIC). The purpose of this study was to introduce a new approach for the treatment of progressive familial intrahepatic cholestasis (PFIC) to avoid ostoma.

Case Presentation:

An 11-year-old girl with the diagnosis of PFIC underwent cholecystoappendicostomy with myotomy operation. Because of anastomosis stricture, she was reoperated with cholecystojejunocolic anastomosis and intussuscepted valve surgery. She was followed for 9 months. Despite disappointing outcomes of internal drainage with cholecystoappendicostomy, results of cholecystojejunocolic anastomosis with intussuscepted valve surgery were promising.

Discussion:

The cholecystojejunocolic anastomosis with intussuscepted valve surgery could be considered as a forthcoming approach in the treatment of intrahepatic cholestasis.     

First report of isolation of Mycobacterium novocastrense from water supplies

We herein present the first documented report associated with the isolation of Mycobacterium novocastrense from environment. The identification and characterization of four unrelated isolates, one from the surface water and the other three from hospital water, were achieved by various conventional and molecular tests including a genus‐specific PCR for Mycobacterium based on 65‐kDa heat shock protein (hsp) gene and 16S rDNA sequencing. Our findings might shed further light on the natural habitat of this rare Mycobacterium.     

Biomechanical Assessment of Brain Dynamic Responses Due to Blast Pressure Waves

A mechanized and integrated computational scheme is introduced to determine the human brain responses in an environment where the human head is exposed to explosions from trinitrotoluene (TNT), or other high-yield explosives, in military applications. The procedure is based on a three-dimensional (3-D) non-linear finite element method (FEM) that implements a simultaneous conduction of explosive detonation, shock wave propagation, blast–head interactions, and the confronting human head. The processes of blast propagation in the air and blast interaction with the head are modeled by an Arbitrary Lagrangian–Eulerian (ALE) multi-material FEM formulation, together with a penalty-based fluid/structure interaction (FSI) algorithm. Such a model has already been successfully validated against experimental data regarding air-free blast and plate–blast interactions. The human head model is a 3-D geometrically realistic configuration that has been previously validated against the brain intracranial pressure (ICP), as well as shear and principal strains under different impact loadings of cadaveric experimental tests of Hardy et al. [Hardy W. N., C. Foster, M. Mason, S. Chirag, J. Bishop, M. Bey, W. Anderst, and S. Tashman. A study of the response of the human cadaver head to impact. Proc. 51 ^st Stapp. Car Crash J. 17–80, 2007]. Different scenarios have been assumed to capture an appropriate picture of the brain response at a constant stand-off distance of nearly 80 cm from the core of the explosion, but exposed to different amounts of a highly explosive (HE) material such as TNT. The overpressures at the vicinity of the head are in the range of about 2.4–8.7 atmosphere (atm), considering the reflected pressure from the head. The methodology provides brain ICP, maximum shear stresses and maximum principal strain within the milli-scale time frame of this highly dynamic phenomenon. While focusing on the two mechanical parameters of pressure, and also on the maximum shear stress and maximum principal strain to predict the brain injury, the research provides an assessment of the brain responses to different amounts of overpressure. The research also demonstrates the ability to predict the ICP, as well as the stress and strain within the brain, due to such an event. The research cannot identify, however, the specific levels of ICP, stress and strain that necessarily lead to traumatic brain injury (TBI) because there is no access to experimental data regarding head–blast interactions.     

Stopping insulin and achieving a good metabolic control in a heavy drinker five months after stopping alcohol

In this case study, we describe a 25 year-old male who showed the symptoms of diabetes after a period of heavy drinking. (HbA1c=13%). Treatment was started with 120 units of insulin. After stopping alcohol consumption and taking an appropriate diet, insulin was tapered down. Five months after the start of treatment, insulin was stopped (HbA1c=5%). The results showed that he was in a good metabolic control after 18 months (HbA1c=5.9%).     

大豆提取物抗戊四唑所致卵巢切除大鼠痉挛的作用（英文）

目的：研究大豆提取物抗戊四唑所致卵巢切除大鼠痉挛的作用。方法：雌性Wistar大鼠随机分为4组（n=15）,分别为假手术组、卵巢切除组、低剂量大豆提取物组和高剂量大豆提取物组。假手术组大鼠行假手术,其余3组大鼠行卵巢切除术。每组大鼠再随机分为2个亚组,其中一个亚组（n=7）每日予低剂量戊四唑（40mg/kg）腹腔内注射,连续14d;另一亚组（n=8）予一次高剂量戊四唑（90mg/kg）腹腔内注射。在戊四唑注射前30min,低剂量大豆提取物（20mg/kg）及高剂量大豆提取物（60mg/kg）组分别腹腔内注射大豆提取物,假手术组及卵巢切除组注射生理盐水。上述步骤完成后,将大鼠置于树脂玻璃箱中观察60min。结果：重复低剂量注射戊四唑14d,卵巢切除组大鼠的痉挛评分在第3、5、8、10、11、12及13天低于假手术组（P〈0.05或P〈0.01）,而低剂量大豆提取物组和高剂量大豆提取物组大鼠的痉挛评分高于卵巢切除组（P〈0.05或P〈0.01）。一次性高剂量注射戊四唑后,与假手术组相比,卵巢切除组大鼠阵发性强直性抽搐潜伏期延长,而最小阵发性痉挛潜伏期无明显变化;与卵巢切除组相比,低剂量及高剂量的大豆提取物显著缩短了大鼠阵发性强直性抽搐及最小阵发性痉挛的潜伏期（P〈0.01）。结论：雌激素能够影响戊四唑所致大鼠痉挛的严重程度,而大豆中所含的植物雌激素也具有类似作用,这种作用还有待更多的研究予以证实。     

Correlation Between Chemical Composition and Antifungal Activity of the Essential Oils of Eight Cinnamomum. Species

Abstract

Fourteen essential oils hydrodistilled from eight Cinnamomum. (Lauraceae) species (C. pubescens. Kochummen, C. impressicostatum. Kosterm, C. microphyllum. Ridl., C. scortechinii. Gamb., C. rhyncophyllum. Miq., C. cordatum. Kosterm, C. zeylanicum. Blume, and C. mollissimum. Hook f.) were examined for their antifungal activity against six dermatophytes (Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. gypseum., and M. audouini)., one filamentous fungi (Aspergillus fumigatus.), and five strains of yeasts (Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis., and Crytococcus neoformans.) by using the broth microdilution method. The antifungal activities of 13 standard compounds that are prevalent constituents in Cinnamomum. oils were also investigated in an effort to correlate the effectiveness of the oils with those of the components of the oils. The chemical composition of the oils was analyzed by GC and GC-MS. Most of the oils showed moderate to strong activity against the fungi. Among the oils, the leaf and bark oils of C. zeylanicum. showed the highest activity against all the fungi with MIC values of 0.04 to 0.63 μ g μ L^{? 1}. Other oils that gave a strong inhibition on fungal growth were the leaf oil of C. cordatum. and bark and twig oils of C. pubescens. and C. impressicostatum.. Cinnamaldehyde, which was the most abundant component of the bark oil of C. zeylanicum., showed the strongest activity against all the fungi studied. Based on the results of the assay on standard samples, it may be that the high levels of cinnamaldehyde, eugenol, geraniol, benzyl benzoate, and methyl cinnamate in the oils and in combination with the minor components is responsible for the high antifungal activity of the oils.     

Nano-delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood–brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.     

Design of a multiplex PCR method for detection of toxigenic-pathogenic in Vibrio cholerae

ObjectiveTo study virulence and regulatory genes (hlyA, ctxB, tcpI) in clinical strains of Vibrio cholerae (V. cholerae), simultaneously.MethodsThree important genes, tcpI, hlyA and ctxB were used for detection of toxigenic and pathogenic V. cholera by chain reaction assay method.ResultsAccording to the results of the PCR, the incidence of hlyA, tcpI, and ctxB genes in clinical isolates was obtained as 94.7% (72 sample), 90.8% (69 sample), and 92.1% (70 sample), respectively. Five strains possessed all genes except ctxB, six strains possessed all genes except tcpI, four strains possessed all genes except hlyA, one strain possessed only hlyA and 60 strains contained a combination of three genes, Including hlyA, ctxB and tcpI.ConclusionsResult show that this method could be reliable to detect toxigenic-pathogenic strains of V. cholerae in Iran.