Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from relapsing-remitting multiple sclerosis patients.

Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-ß: TNF-α and TGF-ß: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.

Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose-derived mesenchymal stem cells.

In type 2 diabetes, dyslipidemia and increased serum free fatty acids (FFAs) exacerbate the development of the disease through a negative effect on insulin secretion. Adipose-derived mesenchymal stem cells (AdMSCs) play a key role in regenerative medicine, and these cells can potentially be applied as novel therapeutic resources in the treatment of diabetes. In this study, AdMSCs were treated with diabetic or nondiabetic serum FFAs isolated from women of menopausal age. Serum FFAs were analyzed using gas-liquid chromatography. The expression level of the stemness markers CD49e and CD90 and the Wnt signaling target genes Axin-2 and c-Myc were evaluated using real-time PCR. The proliferation rate and colony formation were also assessed using a BrdU assay and crystal violet staining, respectively. The level of glutathione was assessed using cell fluorescence staining. Compared to nondiabetic serum, diabetic serum contained a higher percentage of oleate (1.5-fold, p < 0.01). In comparison with nondiabetic FFAs, diabetic FFAs demonstrated decreasing effects on the expression of CD90 (-51%, p < 0.001) and c-Myc (-48%, p < 0.05), and proliferation rate (-35%, p < 0.001), colony formation capacity (-50%, p < 0.01), and GSH levels (-62%, p < 0.05). The negative effect of the FFAs of diabetic serum on the stemness characteristics may impair the regenerative capabilities of AdMSCs.

The porcupine inhibitor WNT974 provokes ectodermal lineage differentiation of human embryonic stem cells.

Porcupine (Porcn) enzyme plays an essential role in Wnt signaling activation. Stearoyl-CoA desaturase-1 (SCD1) is required to provide Porcn substrates. The aim of this study was to determine the effect of a novel Porcn inhibitor on the fate of human embryonic stem cells (hESCs) and the reliance of Porcn on SCD1 activity. hESCs were cultured on a feeder layer or Matrigel-coated plates. Small molecules WNT974 (LGK-974) and CAY10566 were used to inhibit Porcn and SCD1 activity, respectively. We assessed the effect of Porcn inhibition on viability, expression of Wnt signaling targets, pluripotency markers, proliferation, differentiation, and protein fatty acylation. hESCs' conditioned medium (CM) containing secreted Wnt proteins were applied in rescue experiments. To examine the catalytic dependency of Porcn on SCD1, the results of combined inhibitor treatment were compared with the SCD1 inhibitor alone. LGK-974 at the selected concentrations showed mild effects on hESCs viability, but significantly reduced messenger RNA and protein expression of Wnt signaling targets (Axin-2 and c-Myc) and pluripotency markers (OCT-4 and SOX-2) (p < .05). Adding 1 µM of Porcn inhibitor reduced proliferation (p = .03) and enhanced differentiation capacity into ectodermal progenitors (p = .02), which were reverted by CM. Click chemistry reaction did not show significant alteration in protein fatty acylation upon LGK-974 treatment. Moreover, combined inhibitor treatment caused no further substantial reduction in Wnt signaling targets, pluripotency markers, and protein fatty acylation relative to CAY10566-treated cultures. The substrate availability for Porcn activity is regulated by SCD1 and targeting Porcn by LGK-974 prompts the transition of hESCs from self-renewal state to ectodermal lineage.

Advances in microfabrication technologies in tissue engineering and regenerative medicine.

BACKGROUND: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close-to-native three-dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. METHODS: In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self-assembly of microstructures, microfluidics, fiber spinning, and bioprinting. RESULTS: These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. CONCLUSIONS: This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications.

Micro and Nanoscale Technologies for Diagnosis of Viral Infections.

Viral infection is one of the leading causes of mortality worldwide. The growth of globalization significantly increases the risk of virus spreading, making it a global threat to future public health. In particular, the ongoing coronavirus disease 2019 (COVID-19) pandemic outbreak emphasizes the importance of devices and methods for rapid, sensitive, and cost-effective diagnosis of viral infections in the early stages by which their quick and global spread can be controlled. Micro and nanoscale technologies have attracted tremendous attention in recent years for a variety of medical and biological applications, especially in developing diagnostic platforms for rapid and accurate detection of viral diseases. This review addresses advances of microneedles, microchip-based integrated platforms, and nano- and microparticles for sampling, sample processing, enrichment, amplification, and detection of viral particles and antigens related to the diagnosis of viral diseases. Additionally, methods for the fabrication of microchip-based devices and commercially used devices are described. Finally, challenges and prospects on the development of micro and nanotechnologies for the early diagnosis of viral diseases are highlighted.

Network Autoregressive Model for the Prediction of COVID-19 Considering the Disease Interaction in Neighboring Countries.

Predicting the way diseases spread in different societies has been thus far documented as one of the most important tools for control strategies and policy-making during a pandemic. This study is to propose a network autoregressive (NAR) model to forecast the number of total currently infected cases with coronavirus disease 2019 (COVID-19) in Iran until the end of December 2021 in view of the disease interactions within the neighboring countries in the region. For this purpose, the COVID-19 data were initially collected for seven regional nations, including Iran, Turkey, Iraq, Azerbaijan, Armenia, Afghanistan, and Pakistan. Thenceforth, a network was established over these countries, and the correlation of the disease data was calculated. Upon introducing the main structure of the NAR model, a mathematical platform was subsequently provided to further incorporate the correlation matrix into the prediction process. In addition, the maximum likelihood estimation (MLE) was utilized to determine the model parameters and optimize the forecasting accuracy. Thereafter, the number of infected cases up to December 2021 in Iran was predicted by importing the correlation matrix into the NAR model formed to observe the impact of the disease interactions in the neighboring countries. In addition, the autoregressive integrated moving average (ARIMA) was used as a benchmark to compare and validate the NAR model outcomes. The results reveal that COVID-19 data in Iran have passed the fifth peak and continue on a downward trend to bring the number of total currently infected cases below 480,000 by the end of 2021. Additionally, 20%, 50%, 80% and 95% quantiles are provided along with the point estimation to model the uncertainty in the forecast.

A glimpse into molecular mechanisms of embryonic stem cells pluripotency: Current status and future perspective.

Embryonic stem cells have potential differentiation ability into a large variety of cell lineages and proved to be an effective therapeutic modality. However, prolonged in vitro and ex-vivo expansions impair embryonic stem cells multipotentiality, and thereby limit their clinical application. In the past few years, research collected attempts to explore new insights into the molecular mechanisms participate in the stemness capacity of embryonic stem cells. Along with these comments, modalities and strategies with the potential to maintain embryonic stem cells multipotentiality are of great interest. In this review, the authors attempted to discuss the pathways participating in the preservation of embryonic stem cells multipotentiality and emphasized the novel strategies that help to harness regenerative potential.

A mechanical non-enzymatic method for isolation of mouse embryonic fibroblasts.

Mouse embryonic fibroblasts (MEFs) accessibility coupled with their simple generation make them as a typical embryonic cell model and feeder layer for in vitro expansion of pluripotent stem cells (PSCs). In this study, a mechanical isolation technique was adopted to isolate MEFs and the efficiency of this technique was compared with enzymatic digestion method. The suspended MEFs were prepared either by mechanical method or 0.25% trypsin enzymatic digestion. The effect of tissue processing on cell apoptosis/necrosis, morphology, viable cell yield, population doubling time, surface marker expression, and the capacity to support PSCs were determined. The mechanical method yielded a significantly higher number of viable cells. However, it showed similar morphology and proliferation characteristics as compared to enzymatic digestion. The mechanical method induced slight apoptosis in MEFs; however, it did not exert the necrotic effect of trypsinization. Treatment of tissue slurry with trypsin solution caused cell lysis and subsequently cell clump formation. Mechanically isolated cells exhibited a higher expression of the MEF surface antigens Sca1, CD106, and CD105. The PSCs on mechanically isolated MEFs displayed a higher expression of pluripotency genes, and formed more compact colonies with a stronger tendency to crowding compared with those cultured on cells isolated by enzymatic digestion. The mechanical method based on tissue inter-syringe processing is relatively a rapid and simple method for MEF isolation. Compared to the enzymatic digestion, the cells obtained from this method show higher expression of embryonic fibroblasts markers and a more functional capacity in supporting PSCs culture.

Wnt lipidation: Roles in trafficking, modulation, and function.

The Wnt signaling pathway consists of various downstream target proteins that have substantial roles in mammalian cell proliferation, differentiation, and development. Its aberrant activity can lead to uncontrolled proliferation and tumorigenesis. The posttranslational connection of fatty acyl chains to Wnt proteins provides the unique capacity for regulation of Wnt activity. In spite of the past belief that Wnt molecules are subject to dual acylation, it has been shown that these proteins have only one acylation site and undergo monounsaturated fatty acylation. The Wnt monounsaturated fatty acyl chain is more than just a hydrophobic coating and appears to be critical for Wnt signaling, transport, and receptor activation. Here, we provide an overview of recent findings in Wnt monounsaturated fatty acylation and the mechanism by which this lipid moiety regulates Wnt activity from the site of production to its receptor interactions.

Current progress in hepatic tissue regeneration by tissue engineering.

BACKGROUND: Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.

A method for the gross analysis of global protein acylation by gas-liquid chromatography.

Protein acylation is a posttranslational modification in which an amino acid residue of a protein is acylated by a fatty acid. This process plays a key role in regulating proteomic function. Studies of protein acylation have relied on the development and application of extremely complicated molecular methods. However, global protein acylation can be profiled following hydrolysis of fatty acyl groups from cellular proteins. The present study aimed to develop a method for analysis of global protein acylation using gas-liquid chromatography (GLC). The total protein was extracted from the human hepatocellular carcinoma (HepG2) cell line. Protein sedimentation and extensive wash were combined with differential O-, S-, or N-acyl hydrolysis using sodium hydroxide (NaOH), hydroxylamine (NH2 OH), or hydrochloric acid (HCl), respectively. GLC with a flame ionization detector system was used to analyze changes in the fatty acid composition of the released lipids. The effect of selective inhibition of monounsaturated fatty acid (MUFA) synthesis on global protein acylation and the expression of reprogramming markers were determined to further validate the proposed profiling approach. In all hydrolysis conditions, the amount of myristate released was significantly higher than of other fatty acids. Notable differences were observed in the release of individual fatty acids among the hydrolyzing agents. Only NH2 OH could release significant amounts of palmitoleate (>2.5-fold vs. NaOH and HCl). The acylation assay indicates that treatment with a chemical inhibitor of monounsaturated fatty acid synthesis led to an overall increase in saturated fatty acid O- and N-acylation, and a decrease in palmitoleate O- and S-acylation of cellular proteins (<-15%). This was accompanied by significant reductions in the gene expression of the reprogramming markers Oct4 (-26%, P < 0.01) and Sox2 (-40%, P < 0.01). GLC-based analysis of global protein acylation affords a semi-quantitative method that can be used to assess the gross changes in the protein acylation profile during cell differentiation and reprogramming. © 2018 IUBMB Life, 71(3):340-346, 2019.

A Simple Modification Method to Obtain Anisotropic and Porous 3D Microfibrillar Scaffolds for Surgical and Biomedical Applications.

In native tissues, cellular organization is predominantly anisotropic. Yet, it remains a challenge to engineer anisotropic scaffolds that promote anisotropic cellular organization at macroscopic length scales. To overcome this challenge, an innovative, cheap and easy method to align clinically approved non-woven surgical microfibrillar scaffolds is presented. The method involves a three-step process of coating, unidirectional stretching of scaffolds after heating them above glass transition temperature, and cooling back to room temperature. Briefly, a polymer coating is applied to a non-woven mesh that results in a partial welding of randomly oriented microfibers at their intersection points. The coated scaffold is then heated above the glass transition temperature of the coating and the scaffold polymer. Subsequently, the coated scaffold is stretched to produce aligned and three dimentional (3D) porous fibrillar scaffolds. In a proof of concept study, a polyglycolic acid (PGA) micro-fibrillar scaffold was coated with poly(4-hydroxybutirate) (P4HB) acid and subsequently aligned. Fibroblasts were cultured in vitro within the scaffold and results showed an increase in cellular alignment along the direction of the PGA fibers. This method can be scaled up easily for industrial production of polymeric meshes or directly applied to small pieces of scaffolds at the point of care.

Investigation of the relation between bone mass density and serum preptin levels in pre- and postmenopausal women.

Preptin is a peptide hormone co-secreted with insulin and amylin from pancreatic ß cells. It has been demonstrated to have osteogenic effects both in vitro and in vivo. In the present study, serum preptin levels were measured in pre- and postmenopausal women with similar body mass indexes (BMIs) to elucidate its link with bone mineral density (BMD). Sixty women (30 premenopausal and 30 postmenopausal) with low bone mineral density were studied. The BMD scores, serum preptin levels and serum estradiol levels were measured. The correlation between serum preptin and estradiol levels with BMD was assessed. Serum preptin and estradiol levels were significantly lower in the postmenopausal women than the premenopausal subjects [2102.27 ± 918.66 vs. 2667.30 ± 940.41 ng/L (P < 0.05) and 39.32 ± 31.74 vs. 99.24 ± 49.24 pg/ml (P < 0.001), respectively]. The serum preptin levels had weak positive (albeit statistically significant) correlations with estradiol (r = 0.271, P = 0.036), femur neck BMD (r = 0.233, P = 0.035) and total hip BMD (r = 0.287, P = 0.031), but no correlation was observed between serum preptin levels and L1-4 lumbar spine BMD (r = 0.136, P = 0.474). The findings of the present study suggest that serum preptin levels in women decrease after menopause and have a positive correlation with estradiol, femoral and total hip BMDs.

Land Use Regression Models for Alkylbenzenes in a Middle Eastern Megacity: Tehran Study of Exposure Prediction for Environmental Health Research (Tehran SEPEHR).

Land use regression (LUR) has not been applied thus far to ambient alkylbenzenes in highly polluted megacities. We advanced LUR models for benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX using measurement based estimates of annual means at 179 sites in Tehran megacity, Iran. Overall, 520 predictors were evaluated, such as The Weather Research and Forecasting Model meteorology predictions, emission inventory, and several new others. The final models with R2 values ranging from 0.64 for p-xylene to 0.70 for benzene were mainly driven by traffic-related variables but the proximity to sewage treatment plants was present in all models indicating a major local source of alkylbenzenes not used in any previous study. We further found that large buffers are needed to explain annual mean concentrations of alkylbenzenes in complex situations of a megacity. About 83% of Tehran's surface had benzene concentrations above air quality standard of 5 µg/m3 set by European Union and Iranian Government. Toluene was the predominant alkylbenzene, and the most polluted area was the city center. Our analyses on differences between wealthier and poorer areas also showed somewhat higher concentrations for the latter. This is the largest LUR study to predict all BTEX species in a megacity.

Development of Hot Exhaust Emission Factors for Iranian-Made Euro-2 Certified Light-Duty Vehicles.

Emission factors (EFs) are fundamental, necessary data for air pollution research and scenario implementation. With the vision of generating national EFs of the Iranian transportation system, a portable emission measurement system (PEMS) was used to develop the basic EFs for a statistically significant sample of Iranian gasoline-fueled privately owned light duty vehicles (LDVs) operated in Tehran. A smaller sample size of the same fleet was examined by chassis dynamometer (CD) bag emission measurement tests to quantify the systematic differences between the PEMS and CD methods. The selected fleet was tested over four different routes of uphill highways, flat highways, uphill urban streets, and flat urban streets. Real driving emissions (RDEs) and fuel consumption (FC) rates were calculated by weighted averaging of the results from each route. The activity of the fleet over each route type was assumed as a weighting factor. The activity data were obtained from a Tehran traffic model. The RDEs of the selected fleet were considerably higher than the certified emission levels of all vehicles. Differences between Tehran real driving cycles and the New European Driving Cycle (NEDC) was attributed to the lower loading of NEDC. A table of EFs based on RDEs was developed for the sample fleet.

Comparison Between 10- and 14-Day Hybrid Regimens for Helicobacter pylori Eradication: A Randomized Clinical Trial.

BACKGROUND: Helicobacter pylori (H. pylori) eradication has always been a concern. In our previous study, 14-day hybrid regimen showed ideal results. Based on these findings, we decided to compare the efficacy of 10- and 14-day hybrid regimens for H. pylori eradication. METHODS: Two hundred and seventy patients with peptic ulcer disease and H. pylori infection were enrolled in the study. One hundred and thirty-four patients received 10-day hybrid regimen (PACT-10): pantoprazole, 40 mg, and amoxicillin, 1 g, both twice daily for 10 days; plus clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just during the last 5 days. One hundred and thirty-six patients received 14-day hybrid regimen (PACT-14): pantoprazole, 40 mg, and amoxicillin, 1 g, both twice a day for 14 days; plus clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just for the last 7 days. Eight weeks after treatment, (14) C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: Two hundred and fifty patients (124 patients in PACT-10 and 126 patients in PACT-14 regimens) completed the study. The intention-to-treat eradication rates were 77.6% (95% confidence interval (CI): 70.6-84.6%) and 86% (95% CI: 80-92%) for the two regimens, respectively (p = .17). Per-protocol eradication rates were 83.8% (95% CI: 80-86%) and 92.8% (95% CI: 88-96%), respectively (p < .01). There were no significant intergroup differences in compliance to treatment or discontinuation of therapy due to severe side effects. CONCLUSION: Ten-day hybrid regimen could not achieve acceptable eradication rate. However, 14-day hybrid regimen seems to be an acceptable option for H. pylori eradication in Iran.

Comparison of quadruple and triple Furazolidone containing regimens on eradication of helicobacter pylori.

BACKGROUND: The effectiveness of classic standard triple therapy regimen of helicobacter pylori (H. pylori) eradication has decreased to unacceptably low levels, largely related to development of resistance to metronidazole and clarithromycin. Thus successful eradication of H. pylori infections remains challenging. Therefore alternative treatments with superior effectiveness and safety should be designed and appropriately tested in all areas depending on the native resistance patterns. Furazolidone has been used successfully in eradication regimens previously and regimens containing furazolidone may be an ideal regimen. METHODS: H. pylori infected patients with proven gastric or duodenal ulcers and /or gastric or duodenal erosions at Imam Khomeini Hospital in Sari/Northern Iran, were randomly allocated into three groups: group A (OABF) with furazolidone (F) (200 mg bid.), group B (OABM-F) metronidazole (M) (500 mg bid.) for the first five days, followed by furazolidone (F) (200 mg bid.) for the second five days and group C (OAF) with furazolidone (F) (200 mg tid.). Omeprazole (O) (20 mg bid.) and amoxicillin (A) (1000 mg bid.) were given in all groups; bismuth (B) (240 mg bid.) was prescribed in groups A & B. Duration of all eradication regimens were ten days. Eight weeks after treatment, a 14C-urea breath test was performed for evaluation of H. pylori eradication. RESULTS: A total of 372 patients were enrolled in three groups randomly (124 patients in each group); 120 (97%) patients in group A (OABF), 120 (97%) in group B (OABM-F) and 116 (93%) in group C (OAF) completed the study. The intention-to-treat eradication rates were 83.7% (95% CI= 77.3-90.4), 79.8% (95% CI= 72.6-87), and 84.6% (95% CI= 78.2-91.1) and per-protocol eradication rates were 86.6% (95% CI= 80.5-92.8), 82.5% (95% CI= 75.6-89.4), and 90.5% (95% CI= 85.1-95.9) for groups OABF, OABM-F, and OAF, respectively. No statistical significant differences were found in case of severe drug adverse effects between the above mentioned three groups (p> 0.05). The most common side effects, namely nausea and fever, occurred in all groups, but more frequently in group C (OAF) (p< 0.05). CONCLUSION: In developing countries such as Iran, furazolidone-based regimens can substitute clarithromycinbased regimens for H. pylori eradication because of a very low level of resistance, low cost and high effectiveness. Considering per-protocol eradication rate of ten days OAF regimen, and the acceptable limit of ninety percent, we recommend this regimen in developing countries such as Iran to be substituted of classic standard triple therapy. In order to minimize rare serious adverse effects, one week high dose OAF regimen should be taken into consideration in other studies.

Fiber-assisted molding (FAM) of surfaces with tunable curvature to guide cell alignment and complex tissue architecture.

A simple and robust method termed "fiber-assisted molding (FAM)" is presented to create biomimetic three-dimensional surfaces with controllable curvature and helical twist. The alignment of muscle fibrils and the assembly of helically patterned extracellular matrix by cells demonstrate the potential of this method for tissue engineering and other materials science applications.

Exosome Content-Mediated Signaling Pathways in Multiple Sclerosis.

Exosomes are small extracellular vesicles with a complex lipid-bilayer surface and 30-150 nm diameter. These vesicles play a critical role in intercellular signaling networks during physiopathological processes through data trafficking and cell reprogramming. It has been demonstrated that exosomes are involved in a variety of central nervous system (CNS) disorders such as multiple sclerosis (MS). Exosome mediators' cell-to-cell communication is possibly by delivering their contents such as proteins, RNAs (coding and non-coding), DNAs (mitochondrial and genomic), and transposable elements to the target cells. Exosomal microRNAs (miRNAs) differ in their expression patterns in MS disease, thereby providing novel diagnostic and prognostic biomarkers and therapeutic options for better treatment of MS disease. Furthermore, these microvesicles are non-immunogenic and non-toxic therapeutic tools for transferring miRNAs across the blood-brain barrier (BBB). Collectively, exosomes could be used as novel drug delivery devices for the treatment of MS patients. This review summarized research regarding the exosomes from serum, plasma, PBMC, and other cells in MS patients and experimental models. We also provide a critical view of exosome content-mediated signaling pathways in MS, including TNF-α, TGF-ß, NF-κB, and Wnt pathways. The use of exosomes as a therapeutic potential in MS has also been discussed.

Comparison of hybrid and sequential therapies for Helicobacter pylori eradication in Iran: a prospective randomized trial.

BACKGROUND: The eradication of Helicobacter pylori has been always a concern. In the present study, we aimed to compare two novel treatments in Iran. METHOD: Four hundred and twenty patients with peptic ulcer and naïve H. pylori infection were randomized in the study. Two hundred and ten patients received hybrid therapy: pantoprazole 40 mg/b.i.d. and amoxicillin 1 g/b.i.d. for 14 days plus 500 mg clarithromycin and 500 mg tinidazole, both twice daily for the last 7 days. The other 210 patients received sequential therapy: 40 mg pantoprazole/b.i.d. for 10 days and 1 g amoxicillin/b.i.d. for the first 5 days, followed by 500 mg clarithromycin/b.i.d. and 500 mg tinidazole/b.i.d. for the last 5 days. C¹4-urea breath test was performed 8 weeks after the treatment. RESULTS: Three hundred and ninety-six patients (197 patients in the hybrid group and 199 patients in the sequential group) completed the study. The compliance rates were 96.7 and 98.6% for the two groups, respectively. The intention-to-treat eradication rate was 89.5% (95% CI = 85.4-93.6) for the hybrid group and 76.7% (95% CI = 71-82.4) for the sequential group (p = .001), and the per-protocol eradication rates were 92.9% (95% CI = 89.2-96.5) and 79.9% (95% CI = 74.1-85.4) for the hybrid and sequential groups (p = .001), respectively. Severe adverse effects were observed in 2.4% of patients in the hybrid group and 3.8% of those in the sequential group. CONCLUSION: According to our results, sequential regimen does not seem to be an appropriate therapy for H. pylori eradication in the Iranian population, whereas hybrid therapy showed to be more effective. However, considering the high cost of clarithromycin in Iran, we recommend further studies to compare hybrid therapy with bismuth-containing regimens or to assess the effects of hybrid therapies with periods shorter than 14 days.