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Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of parasite antigens on Alzheimer's symptoms in animal model. Alzheimer's model was induced in Wistar rats using Amyloid-beta peptide, and treated with parasite crude antigens from T. gondii RH strain, L. major (MRHO/IR/75/ER), and HC. Spectrophotometry and real-time PCR were used to evaluate the oxidative stress levels, antioxidant enzyme activity, and gene expression of NLRP3, IL-8, IL-1β, and Caspase-1. Histological assays were performed to investigate structural changes in the hippocampus. Apoptosis was analyzed using an Annexin V Apoptosis by Flow cytometer. The levels of total oxidant, antioxidant, and SOD increased in the Alzheimer's group compared with the control group, but these factors were lower in the L. major group. The apoptosis in the treated groups was lower compared to the Alzheimer's group. IL-8 expression was significantly higher in all Alzheimer's groups, but decreased in the HC and L. major treated group compared to Alzheimer's. IL-1β and Caspase-1 expression were similarly increased in all groups compared with the control group, but decreased in the antigen-treated groups compared with Alzheimer's. NLRP3 expression was increased in all groups compared with the control group, with lower expression in HC group, but significantly decreased in L. major group compared with Alzheimer's. In histological results, only L. major group could play a therapeutic role in pathological damage of the hippocampus. The results showed that parasite antigens, specifically L. major antigens, may have neuroprotective effects that reduce oxidative stress, apoptosis, and histopathological changes in response to AD in animal model. [Display omitted] • The states of total oxidant, antioxidant, and SOD were lower in the L. major -treated group. • Apoptosis in the treated groups was lower than that in the Alzheimer's group. • IL-8 expression was significantly higher in all Alzheimer's groups but decreased in the HC and L. major -treated group. • NLRP3 expression was lower in the HC group and significantly decreased in the L. major group compared with Alzheimer's. • The L. major- treated group plays a significant therapeutic role in pathological damage of the hippocampus. [ABSTRACT FROM AUTHOR]

This study evaluated the inhibitory effects of bilirubin on colony formation and cell migration of melanoma and non-melanoma skin cancer cell lines SK-MEL-3 and A431, compared with normal human dermal fibroblasts (HDF). The IC50 obtained from the MTT assay was 125, 100, and 75 μM bilirubin for HDF, A431, and SK-MEL-3 cells, respectively. The colony formation and cell migration of cancer cells, treated with 100 μM bilirubin, were reduced significantly (p < 0.05). Bilirubin decreased cell adhesion and inhibited cell colonization via inducing apoptosis and cell death. Also by interaction with migration main factors, bilirubin caused inhibition the cell migration. [ABSTRACT FROM AUTHOR]

Background and aims: Infertility is one of the most common problems among couples. Generation of male germ cells from adult stem cells is a current promising priority of researchers. This study aimed to investigate the potential of human umbilical cord mesenchymal stem cells (hUMSCs) on the expression of male germ cell markers after isolating by this method. Methods: The hUMSCs was incubated with retinoic acid, testosterone, and conditioned medium (prepared from testicular cell cultures of 7-day-old mice) during 3 days. The bands were visualized and densitometry was accomplished using LI-COR Biosciences software. Results: The high expression levels of C-KIT, DAZL, PIWIL2, and DDX4 in mRNA and protein levels were observed in treated hUMSCs. Conclusion: Results of reverse transcription polymerase chain reaction (RT-PCR) and western blotting showed that method of isolation had no adverse effects on differentiation potential of hUMSCs. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is one of the most important risk factors for liver failure which can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Approximately 170-200 million (almost 3% of the world's population) people have been reported to have HCV infection worldwide. HCV has six genotypes and multiple subtypes. HCV genotyping and identification of subtypes are critical steps for HCV vaccine development. Materials and Methods: In this community-based study, we aimed to investigate the HCV genotypes in infected patients referring to the laboratory of Hajar Hospital of Shahrekord city (the capital of Chaharmahal and Bakhtiari Province) in Iran from November 21, 2016, to October 21, 2017. During 2016-2017, the sera were obtained from 2377 individuals referring to the laboratory of Hajar Hospital of Shahrekord, Iran. The anti-HCV antibody was tested for all sera by enzyme-linked immunosorbent assay test. Following HCV RNA isolation and cDNA synthesis, HCV genotype detection was performed by quantitative reverse transcription-polymerase chain reaction. Results: Genotypes 3, 1a, and 1b were found in 28.6% (95% confidence interval [CI]: 17.0%-40.0%), 9.5% (95% CI: 2.1%-17.0%), and 3.2% (95% CI: 0.0%-7.6%) of the patients, respectively. In 5 patients (7.9%, 95% CI: 1.1%-14.8%), however, we did not observe any genotypes. We could not find any significant difference between the plasma viral load of infected patients and different genotypes. There was no significant difference either between age groups and genotypes (P > 0.05). Conclusion: The findings of the present study determined that HCV genotype 3 was the predominant genotype followed by the genotypes 1a and 1b in Chaharmahal and Bakhtiari Province. [ABSTRACT FROM AUTHOR]

Background: There is rare study on the association between FimH and kidney stone formation in our country. Objectives: Here we studied on stones and identified the bacteria in stones isolated from kidney stone disease and/or UTI patients attending to Hashemi-Nejad hospital (Tehran, Iran) to find out a possible correlation between stone composition and the diseases. We also measure the frequency of fimH gene and its related protein in Escherichia coli isolated from the patients to clarify the effect of this gene in kidney stone formation. Patients and Methods: In This observational-descriptive study, 40 kidney stone samples were gathered and the composition of each sample was determined. The frequency of fimH gene and its related protein was measured using PCR and protein extraction from separated E. coli bacteria. Results: The most prevalence of stones belonged to calcium oxalate stones and the most frequent bacterium in kidney stones was E. coli. The frequency of fimH gene in isolated E. coli was 57.14%. Conclusions: Our data indicated that almost all chemical types of kidney stones may involve in UTI and kidney stone formation.We also realized that although E. coli is a non-urea splitting bacteria, it is the most causative microorganism found in urine and stones. Finally we recognized that fimH gene is seen in the majority of kidney stone samples so it may have a role in formation of kidney stone, although it should be more clarified in future studies. [ABSTRACT FROM AUTHOR]

Background and aim: Certain serum levels of microRNAs (miRNAs) throughout the body can be helpful for cancer diagnosis and prognosis. The miRNAs can be secreted from the papillary thyroid cancer (PTC) into the circulatory system. Accordingly, this study aimed to measure the serum levels of miR-146b, miR-155 and miR-375 to evaluate their diagnostic potentials in distinguish of benign from malignant lesions. Materials and methods: The serum levels of miRNAs were measured by real-time quantitative RT-PCR among100 patients with benign thyroid nodules and 30 patients with PTC. Results: The mean miR-375 and miR-155 expression levels in the PTC group were greater when compared with the benign group. The area under the ROC curve (AUC) was estimated at 0.81 for the miR-375 with 0.76% sensitivity and 0.80% specificity to distinguish between benign and PTC lesions. The AUC was calculated to be 0.75 for the miR-155 with 0.69% sensitivity and 0.90% specificity. Conclusion: According to the results of this study, the serum levels of miR-155 and miR-375 were increased in the patients with PTC, which may be useful as alternative seromarkers for the PTC. [ABSTRACT FROM AUTHOR]

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 (p27Kip1) 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. [ABSTRACT FROM AUTHOR]

Background: Cancer, as a complex, heterogeneous disease, is currently affecting millions of people worldwide. Even if the most common traditional treatments, namely, chemotherapy (CTx) and radiotherapy (RTx), have been so far effective in some conditions, there is still a dire need for novel, innovative approaches to treat types of cancer. In this context, oncoviruses are responsible for 12% of all malignancies, such as human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), as well as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the poorest in the world also account for 80% of all human cancer cases. Against this background, nanomedicine has developed nano-based drug delivery systems (DDS) to meet the demand for drug delivery vectors, e.g., extracellular vesicles (EVs). This review article aimed to explore the potential of engineered small EVs (sEVs) in suppressing human oncovirus-associated cancers. Methods: Our search was conducted for published research between 2000 and 2022 using several international databases, including Scopus, PubMed, Web of Science, and Google Scholar. We also reviewed additional evidence from relevant published articles. Results: In this line, the findings revealed that EV engineering as a new field is witnessing the development of novel sEV-based structures, and it is expected to be advanced in the future. EVs may be further exploited in specialized applications as therapeutic or diagnostic tools. The techniques of biotechnology have been additionally utilized to create synthetic bilayers based on the physical and chemical properties of parent molecules via a top-down strategy for downsizing complicated, big particles into nano-sized sEVs. Conclusion: As the final point, EV-mediated treatments are less toxic to the body than the most conventional ones, making them a safer and even more effective option. Although many in vitro studies have so far tested the efficacy of sEVs, further research is still needed to develop their potential in animal and clinical trials to reap the therapeutic benefits of this promising platform. [ABSTRACT FROM AUTHOR]

Background: Colon cancer is the third most common cancer and the fourth leading cause of death from cancer. Some parasites are introduced as an antineoplastic agents that can inhibit the progress of some cancers. The aim of this study was to investigate the effect of crude hydatid cyst fluid (HCF) on clone cancer cell line (C26). Methods: HCF was isolated from hydatid cysts by syringe, and at the first, its toxicity was obtained by 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis and apoptosis were measured by flow cytometer, and also the expression of Bcl-2 Associated X-protein (BAX) and B-cell lymphoma-2 (BCL2) genes was measured by quantitative reverse transcription PCR. Results: The amount of apoptosis was increased in B antigen-treated cell lines in comparison with the control group. Also, the expression of BAX was increased in the treated group, while the BCL2 expression was decreased in comparison with the control one. Cell cycle analysis in the antigen-treated group compared to the other groups showed that the cells were more in the G0/G1 phase, as well as in the G2/M phase, and fewer cells were in the synthesis phase. Conclusion: Our finding showed that HCF possibly contains active compounds and can limit the growth and development of C26 cell line by reducing or increasing the genes involved in apoptosis and finally the effect on the cell cycle. [ABSTRACT FROM AUTHOR]

Background: Exosomes are the smallest group of extracellular vesicles in size from 30 to 150 nm, surrounded by a lipid bilayer membrane, and originate from multivesicular bodies secreted by different types of cells, such as virus-infected cells. The critical role of exosomes is information transfer among cells, representing a unique way for intercellular communication via a load of many kinds of molecules, including various signaling proteins and nucleic acids. In this review, we aimed to comprehensively investigate the role of exosomes in promoting human oncogenic viruses-associated cancers. Methods: Our search was conducted for published researches between 2000 and 2022 by using several international databases includeing Scopus, PubMed, and Web of Science as well as Google scholar. We also reviewed additional evidence from relevant published articles. Results: It has been shown that exosomes can create the conditions for viral spread in viral infections. Exosome secretion in a human tumor virus can switch on the cell signaling pathways by transferring exosome-encapsulated molecules, including viral oncoproteins, signal transduction molecules, and virus-encoded miRNAs, into various cells. Conclusion: Given the role of exosomes in viruses-associated cancers, they can also be considered as molecular targets in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful. • This study focused on designing a multi-epitope vaccine against HCV. • The conserved regions of the E2 protein were used to predict epitopes. • A vaccine was constructed by joining epitopes, linkers, and an adjuvant. • The vaccine was found to be antigenic, non-toxic, and non-allergenic. • The vaccine revealed a stable molecular interaction with innate immune receptors. [ABSTRACT FROM AUTHOR]

• Exosomes are small vesicles that can transfer biological molecules, horizontally and function in local and systemic cellular communication. • Exosomes cane used as a diagnostic biomarker and therapeutic tool in which they do not possess risks such as aneuploidy and transplant rejection. • An important application of exosomes is their therapeutic potential in clinical trials and used as vaccines in cancers anti-tumor immunotherapy. • Due to the different exosomal miRNA profile, they have potential in the diagnosis of the pathological state and tumor development process. Exosomes are cup-shaped structures, made of two lipid layers. Their size is in the range of 30–150 nm. Exosomes are excreted to the extracellular space and function in local and systemic cellular communication. Based on their primary origins, they can contain substantial amounts of RNA, protein, and miRNA; the horizontal transfer of these contents significantly determines the exosome's biological effects. The endosomal origins of exosomes can be deduced based on their surface protein markers. The use of exosomes as a diagnostic biomarker and therapeutic tool, has numerous advantages because they do not pose risks such as aneuploidy and transplant rejection. This - overview highlights the recent findings in exosome development and current knowledge in exosome-based therapies. [ABSTRACT FROM AUTHOR]

Thyroid cancer is a rare malignancy and accounts for less than 1% of malignant neoplasms in humans; however, it is the most common cancer of the endocrine system and responsible for most deaths from endocrine cancer. Long non-coding (Lnc)RNAs are defined as non-coding transcripts that are more than 200 nucleotides in length. Their expression deregulation plays an important role in the progress of cancer. These molecules are involved in physiologic cellular processes, genomic imprinting, inactivation of chromosome X, maintenance of pluripotency, and the formation of different organs via changes in chromatin, transcription, and translation. LncRNAs can act as a tumor suppressor genes or oncogenes. Several studies have shown that these molecules can interact with microRNAs and prevent their binding to messenger RNAs. Research has shown that these molecules play an important role in tumorigenicity, angiogenesis, proliferation, migration, apoptosis, and differentiation. In thyroid cancer, several lncRNAs (MALAT1, H19, BANCR, HOTAIR) have been identified as contributing factors to cancer development, and can be used as novel biomarkers for early diagnosis or even treatment. In this article, we study the newest lncRNAs and their role in thyroid cancer. [ABSTRACT FROM AUTHOR]

The treatment of Klebsiella pneumoniae is faced with challenges demanding the development of a vaccination strategy. However, no approved and globally available vaccine exists yet. This study aimed to systematically review all published data on K. pneumoniae vaccines in animal models. Without time restrictions, electronic databases were searched using appropriate keywords. The retrieved studies were screened and the data of those that matched our inclusion criteria were collected and analyzed. In total, 2027 records were retrieved; of which 35 studies were included for systematic review. The most frequently used animal model was BALB/c mice. Proteins, polysaccharides, and their combinations (conjugates) were the most common vaccine candidates used. The amount of antigen, the route used for immunization, and the challenge strategy was varying in the studies and were chosen based on several factors such as the animal model, the type of antigen, and the schedule of immunization. Almost all studies claimed that their vaccine was effective/protective, indicated by increasing survival rate, reducing organ bacterial load, and eliciting protective antibody and/or cytokine responses. Altogether, the information presented here will assist researchers to have a better look at the K. pneumoniae vaccine candidates and to take more effective steps in the future. • We systematically reviewed published data on Klebsiella pneumonia vaccines. • Thirty five studies on animal models were included. • The detailed data of immunization, challenge and outcome of studies is presented. • The provided data makes a better look at the K. pneumoniae vaccine candidates. [ABSTRACT FROM AUTHOR]