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Multiple sclerosis (MS) is an inflammatory disease related to the central nervous system (CNS) with a significant global burden. In this illness, the immune system plays an essential role in its pathophysiology and progression. The currently available treatments are not recognized as curable options and, at best, might slow the progression of MS injuries to the CNS. However, stem cell treatment has provided a new avenue for treating MS. Stem cells may enhance CNS healing and regulate immunological responses. Likewise, stem cells can come from various sources, including adipose, neuronal, bone marrow, and embryonic tissues. Choosing the optimal cell source for stem cell therapy is still a difficult verdict. A type of stem cell known as mesenchymal stem cells (MSCs) is obtainable from different sources and has a strong immunomodulatory impact on the immune system. According to mounting data, the umbilical cord and adipose tissue may serve as appropriate sources for the isolation of MSCs. Human amniotic epithelial cells (hAECs), as novel stem cell sources with immune-regulatory effects, regenerative properties, and decreased antigenicity, can also be thought of as a new upcoming contender for MS treatment. Overall, the administration of stem cells in different sets of animal and clinical trials has shown immunomodulatory and neuroprotective results. Therefore, this review aims to discuss the different types of stem cells by focusing on MSCs and their mechanisms, which can be used to treat and improve the outcomes of MS disease. [ABSTRACT FROM AUTHOR]

Background: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen expressed on many types of cancer cells, but not normal adult cells. ROR1 antigen contributes to cancer development and progression by several signaling pathways. ROR1 expression has been associated with tumor growth, survival, and metastasis. In this study specific human recombinant antibodies were selected against ROR1 antigen for their use in cancer immunotherapy. Methods: Phage display technology was used to produce phage antibody from a human scFv library. Phage concentration was determined to confirm the phage rescue process. Panning procedure was performed to isolate specific scFv clones against ROR1 epitope. Phage ELISA was done to evaluate the reactivity of the selected scFvs. Results: Two specific human scFvs with frequencies of 20% and 25% were selected against ROR1 peptide. The antibodies showed specific reaction to the corresponding epitopes in phage ELISA. Conclusions: Cancer targeted therapy using human specific antibodies is a new strategy, which is used in cancer therapy. The selected specific scFvs that target ROR1 epitope are human antibodies that originated from a human library and have the potential to be used in clinic in cancer immunotherapy of ROR1 positive tumors without induction of human anti mouse antibody (HAMA) response. [ABSTRACT FROM AUTHOR]

Significant progress has been made in HIV-1 research; however, researchers have not yet achieved the objective of eradicating HIV-1 infection. Accordingly, in this study, eucaryotic and procaryotic in silico vaccines were developed for HIV-Gag polyproteins from 100 major HIV subtypes and CRFs using immunoinformatic techniques to simulate immune responses in mice and humans. The epitopes located in the conserved domains of the Gag polyprotein were evaluated for allergenicity, antigenicity, immunogenicity, toxicity, homology, topology, and IFN-γ induction. Adjuvants, linkers, CTLs, HTLs, and BCL epitopes were incorporated into the vaccine models. Strong binding affinities were detected between HLA/MHC alleles, TLR-2, TLR-3, TLR-4, TLR-7, and TLR-9, and vaccine models. Immunological simulation showed that innate and adaptive immune cells elicited active and consistent responses. The human vaccine model was matched with approximately 93.91% of the human population. The strong binding of the vaccine to MHC/HLA and TLR molecules was confirmed through molecular dynamic stimulation. Codon optimization ensured the successful translation of the designed constructs into human cells and E. coli hosts. We believe that the HIV-1 Gag vaccine formulated in our research can reduce the challenges faced in developing an HIV-1 vaccine. Nevertheless, experimental verification is necessary to confirm the effectiveness of these vaccines in these models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hashempour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system(CNS). It is widely accepted that the development and progression of MS result from aberrant activation of potentially encephalitogenic reactive-T cells against CNS antigens. The pathologic roles of both CD4+ (T helper; Th) and CD8+ T cells have been demonstrated in MS lesions., Objective: In the present work, we applied a series of bioinformatics tools to design a dendritic cell (DC)-targeting Tregitope-based multi-epitope vaccine for MS to induce tolerance in pathogenic myelin-specific T cells., Methods: The 3D structure of anti-DEC205 scFv and the remaining part of the vaccine were modeled by ROSIE Antibody server and ITASSER software, respectively. AIDA web server (ab initio domain assembly server) was applied to assemble two parts of the vaccine and build the full construct. Following modeled structure refinement and validation, physicochemical properties, and allergenicity of the vaccine were assessed. In the final step, in silico cloning was done to ensure high-level expression in the desired host., Results: This vaccine consists of three main parts; 1) Anti-DEC205 scFv antibody, 2) multiepitope vaccine part composed of multiple pathogenic CD4+, and CD8+ T cell epitopes originated from multiple known antigens in MS patients, as well as T-regulatory (Treg)-inducing epitopes (Tregitopes), and 3) vasoactive intestinal peptide (VIP). All parts of the final vaccine were joined together with the help of proper linkers. After vaccine construction, the three-D structure, as well as different physicochemical and immunological features of the vaccine were predicted. Finally, in silico gene cloning was also carried out to assure efficient production of protein vaccine in Escherichia coli K12 expression strain., Conclusion: Computational study revealed that this vaccination can regulate MS disease progression and even relapse by harnessing pathogenic T cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of hospitalization of infants and young children and also one of the main causes of morbidity and mortality in immuno-compromised and transplant patients. Despite many efforts, there is currently no specific anti-HPIV-3 drug or approved vaccine to prevent and control the virus. Identification of HPIV-3 epitopes with the capability of binding to human leukocyte antigen (HLA) class II molecules can be helpful in designing new vaccine candidates against HPIV-3 infection, and also can be useful for the in vitro stimulation and proliferation of HPIV-3-specific T cells for transplant and immunocompromised patients., Objective: To predict and comprehensively evaluate CD4 + T cell epitope (HLA-II binders) from four main HPIV-3 antigens., Methods: In the present work, we predicted and comprehensively evaluated CD4 + T cell epitope (HLA-II binders) from four main HPIV-3 antigens, including fusion protein (F), hemagglutininneuraminidase (HN), nucleocapsid (N) and matrix (M) proteins using bio- and immunoinformatics software. The toxicity, allergenicity, Blast screening and population coverage of the predicted epitopes were evaluated. The binding ability of the final selected epitopes was evaluated via a docking study., Results: After several filtering steps, including blast screening, toxicity and allergenicity assay, population coverage and docking study, 9 epitopes were selected as candidate epitopes. The selected epitopes showed high population coverage and docking studies revealed a significantly higher binding affinity for the final epitopes in comparison with the negative control peptides., Conclusion: The final selected epitopes could be useful in designing vaccine candidates and for the treatment of immune-compromised individuals and patients with transplantation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood, but genetics and environmental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormalities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic lowgrade inflammatory state. The inflammatory milieu can negatively affect the CNS and promote MS pathogenesis due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. By crossing the blood-brain barrier, the pro-inflammatory adipokines such as leptin, resistin, and visfatin activate the CNS-resident immune cells, and promote the inflammatory responses; subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, better knowledge of the adipokines' role in the induction of obesity-related chronic inflammation and subsequent events leading to the dysfunctional blood-brain barrier is essential. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, and the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier permeability in MS patients, has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Pro- inflammatory cytokines including Interleukin (IL)-18 have been shown to be involved in the clearance of Hepatitis C virus (HCV) infection. However, changes in the balance of pro- and anti-inflammatory cytokines production during the immune response, can elicit a variety of liver damages. Therefore, it is of interest to study IL-18 serum levels in hepatitis patients and its correlation with HCV infection., Methods: Twenty-nine newly diagnosed HCV+ patients with no history of antiviral therapy, and 17 healthy controls, were enrolled in our study. Biochemical markers of liver disease were evaluated by biochemistry assay kits. Serum concentrations of IL-18 were determined with the ELISA method before and after treatment with pangenotypic direct-acting antivirals (DAAs) treatment., Results: Our results showed statistically significant difference in serum levels of IL-18 in HCV+ patients (692.261 ± 48.76) compared to healthy controls (520.00 ± 44.73) (P=0.021). However, there was no significant difference in IL-18 serum levels between the treated group compared to untreated patients (P=0.74). No significant correlations were detected between the level of IL-18 and liver enzyme levels., Conclusion: According to our study, IL-18 might be a disease marker associated with HCV infection; however, this conclusion requires further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The article has been withdrawn at the request of the authors of the journal Protein & Peptide Letters. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policiesmain. php., Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net)

Aim: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG). Methods: The three-dimensional structure of anti ROR1 scFv-EndoG protein was modeled and structure validation tools were employed to confirm the accuracy and reliability of the developed model. In addition, stability and integrity of the model were assessed by molecular dynamic (MD) simulation. Results: All results suggested the protein model to be acceptable and of good quality. Conclusions: Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1 extracellular domain by its scFv portion and selectively deliver non-immunogenic human endonuclease G enzyme as an end-stage apoptosis molecule into ROR1-expressing cancer cells and lead rapidly to apoptosis. We believe that anti ROR1 and other anti-tumor antigen scFv-EndoG forms may be helpful for cancer therapy., (Creative Commons Attribution License)

Objectives: In order to identify genes with the greatest contribution to bladder cancer, we proposed a sparse model making the best discrimination from other patients. Methods: In a cross-sectional study, 22 genes with a key role in most cancers were considered in 21 bladder cancer patients and 14 participants of the same age (± 3 years) without bladder cancer in Shiraz city, Southern Iran. Real time-PCR was carried out using SYBR Green and for each of the 22 target genes 2-Δct as a quantitative index of gene expression was reported. We determined the most affective genes for the discriminant vector by applying penalized linear discriminant analysis using LASSO penalties. All the analyses were performed using SPSS version 18 and the penalized LDA package in R.3.1.3 software. Results: Using penalized linear discriminant analysis led to elimination of 13 less important genes. Considering the simultaneous effects of 22 genes with important influence on many cancers, it was found that TGFβ, IL12A, Her2, MDM2, CTLA-4 and IL-23 genes had the greatest contribution in classifying bladder cancer patients with the penalized linear discriminant vector. The receiver operating characteristic (ROC) curve revealed that the proposed vector had good performance with minimal (only 3) mis- classification. The area under the curve (AUC) of our proposed test was 96% (95% CI: 83%- 100%) and sensitivity, specificity, positive and negative predictive values were 90.5%, 85.7%, 90.5% and 85.7%, respectively. Conclusions: The penalized discriminant method can be considered as appropriate for classifying bladder cancer cases and searching for important biomarkers., (Creative Commons Attribution License)