Human placental extract attenuates neurological symptoms in the experimental autoimmune encephalomyelitis model of multiple sclerosis-A putative approach in MS disease?

Background: Different studies have demonstrated the anti-inflammatory effects of human placental extract both in vivo and in vitro. Considering the chronic inflammatory nature of multiple sclerosis (MS) disease, we examined whether or not the administration of human placental extract is able to attenuate the neurological symptoms detected in experimental autoimmune encephalomyelitis (EAE) model of MS. Methods: The injected myelin oligodendrocyte glycoprotein (MOG) induced EAE in mice, and treatment began from day 4 post-injection by intraperitoneal administration of 0.2 mg/kg human placental extract, repeated every other day up to day 31 post-injection. At the end of the treatment, luxol fast blue (LBS) staining and hematoxylin and eosin (H&E) staining were performed to evaluate the demyelination of neurons and inflammatory responses, respectively. Further assessed were the serum concentrations of IL-23 and IL-27. Results: The administration of human placental extract was able to significantly reduce the mean clinical score in EAE mice, decrease the pro-inflammatory process and attenuate neural demyelination. Moreover, while the serum concentration of IL-23 was significantly diminished in the EAE mice receiving human placental extract compared to the non-Treated EAE group, IL-27 concentration was significantly increased. Conclusions: Our findings demonstrated the administration of human placental extract could significantly attenuate the neurological symptoms in the EAE model of MS in part through modulating the serum levels of IL-23 and IL-27 and enhancing neuroprotection and myelin repair. © 2020 BioMed Central Ltd.. All rights reserved

Helicobacter pylori release from yeast as a vesicle-encased or free bacterium

Background: Yeast has been suggested as a potent reservoir of H. pylori that facilitates bacterial spread within human populations. What mechanism ensures effective H. pylori release from yeast? Here, H. pylori release from yeast as a vesicle-encased or free bacterium was studied. Materials and methods: Liquid culture of Candida yeast was examined by light, fluorescence and transmission electron microscopy methods to observe the released vesicles. Vesicles were isolated and examined by TEM. Immunogold labeling was used for detection of H. pylori-specific proteins in vesicles� membrane. Free bacterial cells, released from yeast, were separated by immunomagnetic separation and observed by field emission scanning electron microscopy (FESEM). DNA of bead-bound bacteria was used for amplification of H. pylori-16S rDNA. Viability of bead-bound bacteria was examined by live/dead stain and cultivation on Brucella blood agar. Results: Microscopic observations showed that vesicles contained bacterium-like structures. Thin sections showed release of vesicle-encased or free bacterium from yeast. Immunogold labeling revealed occurrence of H. pylori proteins in vesicles� membrane. FESEM showed attachment of H. pylori cells to magnetic beads. Sequencing of 521 bp PCR product confirmed the identity of bead-bound H. pylori. Live/dead staining showed viability of bead-bound H. pylori but the result of culture was negative. Conclusions: Escape of intracellular H. pylori from yeast as a membrane-bound or free bacterium indicates that H. pylori uses safe exit mechanisms that do not damage the host which is the principle of symbiotic associations. In human stomach, certain conditions may stimulate yeast cells to release H. pylori as a vesicle-encased or free bacterium. © 2020 John Wiley & Sons Lt

Various methods of gold nanoparticles (GNPs) conjugation to antibodies

The unique properties of gold nanoparticles, their rich surface chemistry, and low toxicity as well as easy methods of synthesis have promoted conjugation of the particles with numerous biomolecules for site-specific delivery. Gold nanoparticles have multiple applications including photoablation, diagnostic imaging, radiosensitization, vaccine development, antioxidant, and multifunctional drug-delivery vehicles.These applications require an increasingly complex level of surface decoration in order to achieve efficacy, and limit off-target toxicity. This review will discuss the chemical and physical approaches commonly utilized in relation to surface decoration and the powerful system used to indicate success of the conjugation. Finally, we review the range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic. © 2016 The Authors

Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-Naïve chronic HBV patients

Background: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. Objectives: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. Materials and Methods: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. Conclusions: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option. © 2013, KOWSAR Corp

Investigation of CTNNB1 gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1 showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4) rather than HBV-related cases (12.7, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC. © 2020 The Author(s)

Evolution of hepatitis B virus surface gene and protein among Iranian chronic carriers from different provinces

Background and Objectives: Iranian chronic HBV carrier�s population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. Materials and Methods: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. Results: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3 and 96, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6 and 68.8, respectively). Kermanshah province contained only 5.2, whereas Isfahan had 54.5 of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58 (Fars) to 46.6 (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6 (Khuzestan) and 63 (Kermanshah). Conclusion: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues. © 2015, Tehran University of Medical Science. All rights reserved

Iranian joint registry (iranian national hip and knee arthroplasty registry)

Periodic evaluation and monitoring the health and economic outcome of joint replacement surgery is a common and popular process under the territory of joint registries in many countries. In this article we introduce the methodology used for the foundation of the National Iranian Joint Registry (IJR) with a joint collaboration of the Social Security Organization (SSO) and academic research departments considering the requirements of the Iran's Ministry of Health and Education. ©BY THE ARCHIVES OF BONE AND JOINT SURGERY

Scale-dependent non-Gaussianity and the CMB power asymmetry

We introduce an alternative parametrisation for the scale dependence of the non–linearity parameter fNL in quasi-local models of non–Gaussianity. Our parametrisation remains valid when fNL changes sign, unlike the commonly adopted power law ansatz fNL(k) ∝ knfNL. We motivate our alternative parametrisation by appealing to the self-interacting curvaton scenario, and as an application, we apply it to the CMB power asymmetry. Explaining the power asymmetry requires a strongly scale dependent non-Gaussianity. We show that regimes of model parameter space where fNL is strongly scale dependent are typically associated with a large gNL and quadrupolar power asymmetry, which can be ruled out by existing observational constraints

The hemispherical asymmetry from a scale-dependent inflationary bispectrum

If the primordial bispectrum is sufficiently large then the CMB hemispherical asymmetry may be explained by a large-scale mode of exceptional amplitude which perturbs the zeta two-point function. We extend previous calculations, which were restricted to one- or two-source scenarios, by providing a method to compute the response of the two-point function in any model yielding a 'local-like' bispectrum. In general, this shows that it is not the reduced bispectrum fNL which sources the amplitude and scale-dependence of the mode coupling but rather a combination of 'response functions'. We discuss why it is difficult to construct successful scenarios and enumerate the fine-tunings which seem to be required. Finally, we exhibit a concrete model which can be contrived to match the observational constraints and show that to a Planck-like experiment it would appear to have |fNL-local| ~ |fNL-equi| ~ |fNL-ortho| ~ 1. Therefore, contrary to previous analyses, we conclude that it is possible to generate the asymmetry while respecting observational constraints on the bispectrum and low-ell multipoles even without tuning our location on the long-wavelength mode

Hepatitis B virus genotype D is the only genotype circulating in Iranian chronic carriers, the unique pattern of genotypic homogeneity

Aim: To characterize the hepatitis B virus surface protein genotypes and sequence variations among HBsAg positive chronic Iranian patients from different ethnic groups. Method: The surface genes from 312 patients were amplified and directly sequenced. Results: All strains (100) belonged to genotype D and subtypes ayw2. The average nucleotide mutation frequency was 0.91 (dN/dS < 1.0), indicated negative selection. There was no significant correlation between HBV DNA and ALT levels and the occurrence of amino acid substitutions. However, in terms of HBeAg/Anti-HBe status, the association between both groups for silent nucleotide mutation was strong, indicating selection bias on missense mutations. A higher number of amino acid mutations was found in anti-HBe positive versus HBeAg positive patients.Conclusion: The uniqueness pattern of HBV genetics hemogeniety together with the low mutational frequency indicated that HBV has introduced to Iran recently and isolation of people in the absence of intermixing with other genotypes led to a homologous pattern. © 2014 ACT