Distribution of Serogroup and Antibiotic Resistance Patterns of Shigella Species in Iran, 1984-2018: A systematic Review

Background: Shigellosis is recognized as a global concern by the WHO. Shigella genus includes 4 species of Shigella dysenteriae, Shigella flexneri, Shigella boydii and Shigella sonnei. Geographic distribution and antimicrobial susceptibility patterns of Shigella species are different. Methods: We searched published studies in Science Direct, PubMed, PubMed Central (PMC), Scopus, Google Scholar, and ISI Web of Science, Medlib, Magiran, Iranian Scientific Information Database (SID) and 'IranMedex between 1984 and 2018. Results: Many studies in Iran and elsewhere in the world emphasize the emergence of Shigella resistant species. Most of them have shown high resistance to TMP/STX, tetracycline, ampicillin and streptomycin , and some have resistance to antibiotics such as ciprofloxacin, azithromycin, and tetracyclines have reported. Conclusions: The frequency of Shigella species is very different in different countries. The distribution and prevalence of Shigella species in different countries may depend on the level of economic development, age, and environmental factors

Molecular dynamics mechanisms of the inhibitory effects of abemaciclib, hymenialdisine, and indirubin on CDK-6

Background: Cyclin-Dependent Kinases-6 (CDK-6) is a serine/threonine protein kinase with regular activity in the cell cycle. Some inhibitors, such as abemaciclib, hymenialdisine, and in-dirubin, cause cell arrest by decreasing its activity. Objectives: The purpose of this study was to evaluate the Molecular Dynamic (MD) effects of abe-maciclib, hymenialdisine, and indirubin on the structure of CDK-6. Methods: The PDB file of CDK-6 was obtained from the Protein Data Bank (http://www.rcsb.org). After the simulation of CDK-6 in the Gromacs software, 200 stages of molecular docking were run on CDK-6 in the presence of the inhibitors using AutoDock 4.2. The simulation of CDK-6 in the presence of inhibitors was performed after docking. Results: Abemaciclib showed the greatest tendency to bind CDK-6 via binding 16 residues in the binding site with hydrogen bonds and hydrophobic bonding. CDK-6 docked to hymenialdisine and indirubin increased the Total Energy (TE) and decreased the radius of gyration (Rg). CDK-6 docked to hymenialdisine significantly decreased the coil secondary structure. Conclusion: CDK-6 is inhibited via high binding affinity to abemaciclib, hymenialdisine, and indi-rubin inhibitors and induces variation in the secondary structure and Rg in the CDK-6 docked to the three inhibitors. It seems that developing a drug with a binding tendency to CDK6 that is similar to those of abemaciclib, indirubin, and hymenialdisine can change the secondary structure of CDK6, possibly more potently, and can be used to develop anticancer drugs. However, additional studies are needed to confirm this argument

Comparison of therapeutic effects of encapsulated Mesenchymal stem cells in Aloe vera gel and Chitosan-based gel in healing of grade-II burn injuries

Treatment of burn injuries with Mesenchymal stem cells (MSCs) is a great promise due to their unique properties. As two natural and functional wound dressing, Chitosan and Aloe-Vera gel assist wound regeneration by providing a proper environment. In the current study, we aimed to compare the effect of encapsulated BMSCs in Chitosan-based gel and Aloe-Vera gel on the healing of grade-II burn injuries compared to other groups in the rat. After creation of a 2 � 2 cm grade-II burn on dorsal skin of rats, treatments were performed for each group. The wound closure rate and healing properties were evaluated by histopathological analysis on 7, 14, 21 and, 28 days post-treatment. The expression rate of VEGF, Collagen-I and Collagen-III genes was also assessed on days 3, 7, 14, 21 and 28 performing qRT-PCR. The full wound healing with inconsiderable scar formation was achieved for Aloe-vera/BMSCs and Chitosan/BMSCs group on 28th day post-treatment. Pathological results also demonstrated the highest angiogenesis and granulation tissue formation for Aloe-vera/BMSCs and Chitosan/BMSCs groups respectively. The expression level of VEGF, Collagen-I, and Collagen-III genes was significantly higher in these groups on days 14 and 21, compared to other groups. Results demonstrated the synergistic effect of BMSCs when combined with Chitosan or Aloe-vera gel enhanced the healing process of wound healing more than chitosan gel treatment. Therefore, this gel can be considered as effective approaches for treatment of burn injuries

Frequency of virulence-associated genotypes of Helicobacter pylori and their correlation with clinical outcome and histological parameters in infected patients

Helicobacter pylori (H. pylori) is a gram-negative which can cause several gastroduodenal diseases, including gastritis and peptic ulcer disease (PUD). H. pylori specific genotypes have been related to increased occurrence of gastritis and PUD. The aim of this study was to investigate the clinical relevance of the major virulence factors of H. pylori with clinical outcomes and histological parameters in Iranian patients. Totally, 200 subjects with PUD and gastritis disease who underwent gastroduodenal endoscopy were enrolled in this study. The presence of the cagA, vacA, oipA, babA2, and iceA genes in antral gastric biopsy specimens were determined by polymerase chain reaction (PCR) and the results were compared with clinical outcomes and histological parameters. The frequency of babA2(+), oipA(+), vacA s1/m2, and vacA m2 genes was significantly higher in patients with peptic ulcer disease compared with patients with gastritis. In contrast, the frequency of vacA s1/m1 gene was significantly higher in gastritis subjects than PUD subjects. The high-density scores of H. pylori were strongly associated with iceA1, babA2(+), and oipA(+) genes. Additionally, the high polymorphonuclear cell infiltration and high mononuclear cell infiltration scores were strongly associated with the cagA(+), iceA1, oipA(+) genes and cagA(+), babA2(+), oipA(+) genes, respectively. Our study indicated that the vacA, babA2, and oipA virulence factors are related to a higher risk of PUD in subjects with H. pylori-infection. Infection with these strains was associated with a more severe gastropathy

In silico design of a multi-epitope vaccine against HPV16/18

Background Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. Results In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-gamma production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. Conclusions According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer

Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study

In December 2019, a new virus called SARS-CoV-2 was reported in China and quickly spread to other parts of the world. The development of SARS-COV-2 vaccines has recently received much attention from numerous researchers. The present study aims to design an effective multi-epitope vaccine against SARS-COV-2 using the reverse vaccinology method. In this regard, structural proteins from SARS-COV-2, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, were selected as target antigens for epitope prediction. A total of five helper T lymphocytes (HTL) and five cytotoxic T lymphocytes (CTL) epitopes were selected after screening the predicted epitopes for antigenicity, allergenicity, and toxicity. Subsequently, the selected HTL and CTL epitopes were fused via flexible linkers. Next, the cholera toxin B-subunit (CTxB) as an adjuvant was linked to the N-terminal of the chimeric structure. The proposed vaccine was analyzed for the properties of physicochemical, antigenicity, and allergenicity. The 3D model of the vaccine construct was predicted and docked with the Toll-like receptor 4 (TLR4). The molecular dynamics (MD) simulation was performed to evaluate the stable interactions between the vaccine construct and TLR4. The immune simulation was also conducted to explore the immune responses induced by the vaccine. Finally, in silico cloning of the vaccine construct into the pET-28 (+) vector was conducted. The results obtained from all bioinformatics analysis stages were satisfactory; however, in vitro and in vivo tests are essential to validate these results

Inhibition of MicroRNA miR-222 with LNA Inhibitor Can Reduce Cell Proliferation in B Chronic Lymphoblastic Leukemia

MicroRNAs (miRNAs) are small regulatory molecules that negatively regulate gene expression by base-pairing with their target mRNAs. miRNAs have contribute significantly to cancer biology and recent studies have demonstrated the oncogenic or tumor-suppressing role in cancer cells. In many tumors up-regulation miRNAs has been reported especially miR-222 has been shown to be up-regulated in B chronic lymphocytic leukemia (B-CLL). In this study we assessed the effected inhibition of miR-222 in cell viability of B-CLL. We performed inhibition of mir-222 in B-CLL cell line (183-E95) using locked nucleic acid (LNA) antagomir. At different time points after LNA-anti-mir-222 transfection, miR-222 quantitation and cell viability were assessed by qRT-real time polymerase chain reaction and MTT assays. The data were analyzed by independent t test and one way ANOVA. Down-regulation of miR-222 in B-CLL cell line (183-E95) with LNA antagomir decreased cell viability in B-CLL. Cell viability gradually decreased over time as the viability of LNA-anti-mir transfected cells was <47 % of untreated cells at 72 h post-transfection. The difference in cell viability between LNA-anti-miR and control groups was statistically significant (p < 0.042). Based on our findings, the inhibition of miR-222 speculate represent a potential novel therapeutic approach for treatment of B-CLL

Biopolymer-based scaffolds for corneal stromal regeneration: A review

The stroma is one of the 5 layers of the cornea that comprises more than 90% of the corneal thickness, and is the most important layer for the transparency of cornea and refractive function critical for vision. Any significant damage to this layer may lead to corneal blindness. Corneal blindness refers to loss of vision or blindness caused by corneal diseases or damage, which is the 4th most common cause of blindness worldwide. Different approaches are used to treat these patients. Severe corneal damage is traditionally treated by transplantation of a donor cornea or implantation of an artificial cornea. Other alternative approaches, such as cell/stem cell therapy, drug/gene delivery and tissue engineering, are currently promising in the regeneration of damaged cornea. The aim of tissue engineering is to functionally repair and regenerate damaged cornea using scaffolds with or without cells and growth factors. Among the different types of scaffolds, polymer-based scaffolds have shown great potential for corneal stromal regeneration. In this paper, the most recent findings of corneal stromal tissue engineering are reviewed

Evaluating the Effects of Molecular Dynamic And Docking of Abemaciclib, Hymenialdisine, and Indirubin on CDK-2 Inhibition by Simulation Study

Background & objectives: Cyclin-dependent kinase 2 (CDK-2) is a serine/threonine protein kinase with regulatory activity in the cell cycle. Inhibitors of this protein are the treatment of choice for a variety of cancers by stopping the cell cycle. In this in silico study, the effects of docking and molecular dynamics of Abemaciclib, Hymenialdisine, and Indirubin on the inhibition of CDK-2 as one of the most important factors in the cell cycle have been investigated. Methods: PDB file of CDK-2 protein as well as three-dimensional structures of Abemaciclib, Hymenialdisine, and Indirubin were obtained from the protein database (http://www.rcsb.org) and pubchem server, respectively. After simulating CDK-2 in Gromacs software, molecular docking of compounds on CDK-2 was performed by AutoDock 4.2 software. Finally, the most important molecular dynamics factors such as RMSD,the radius of gyration and total energy in the pre-docking state were analyzed and compared to these factors in the post-docking stage. Results: Abemaciclib has the highest affinity for binding to amino acids at the CDK-2 binding site by releasing binding energy equivalent to 8.23 kJ/mol. The binding of Abemaciclib, Hymenialdisine, and Indirubin to CDK-2, resulted in significant reductions in some molecular dynamics factors such as mean total energy, the radius of gyration, RMSD, and changes in CDK-2 secondary structure. Conclusion: Abemaciclib, Hymenialdisine, and Indirubin have a high tendency to interact with CDK-2, and this binding can induce significant dynamic molecular changes in the structure of CDK-2 molecule. Based on the results of molecular dynamics simulation, the secondary structure of CDK-2 changes after each ligand binds to it and makes the complex of ligand and protein more stable. Article number: 4 Keywords: CDK-2, Abemaciclib, Hymenialdisin, Indirubin, Molecular Dynamic Simulatio

Decreased cell proliferation and induced apoptosis in human B-chronic lymphocytic leukemia following miR-221 inhibition through modulation of p27 expression

Background This study aimed to investigate the effects of the miR-221 inhibition on the human B-chronic lymphocytic leukemia (B-CLL) cell viability and the p27 gene expression, to introduce a new treatment approach for this type of cancer. In this context, the cyclin-dependent kinase (Cdk) inhibitor 1B (p27(Kip1)) is considered as an enzyme inhibitor that encodes a protein belonging to the Cip/Kip family of the Cdk inhibitor proteins. Methods The affected miR-221 inhibition in the B-CLL cell viability was initially assessed. The inhibition of miR-221 in the B-CLL cell line (183-E95) was thus performed using locked nucleic acid (LNA) as an antagomir. After the LNA-anti-miR-221 transfection, the miR-221 quantification, cell viability, and apoptosis assays were evaluated at different intervals by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and flow cytometry (FC), respectively. The qRT-PCR was also completed for the p27 gene. The data were subsequently analyzed by independent-samples t-test and one-way analysis of variance (ANOVA). Results A gradual reduction was observed in the B-CLL cell viability, and consequently the transfected LNA-anti-miR cell viability reached below 55% of the untreated cells after 72 h of transfection. A statistically significant difference was found in the cell viability between the LNA-anti-miR-treated and control groups (p-value <= 0.043). The downregulation of miR-221 in the B-CLL (183-E95) cells was further conducted by LNA-anti-miR-221. Conclusion The miR-221 inhibition significantly decreases cell viability through augmenting the p27 gene expression and inducing apoptosis. Moreover, the findings demonstrated that the inhibition of miR-221 might be a new treatment approach for B-CLL, although more confirmation is needed by investigating appropriate animal models