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Abstract Background Cutibacterium acnes ( C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer’s disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons. Methods In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ1–42) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated. Results C. acnes-infected rats displayed memory deficits and Aβ1–42 deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals. Conclusion Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites. Graphical Abstract

Abstract Background The development of new strategies to inhibit and/or treat osteoporosis as a chronic systemic disease is one of the most crucial topics. The present study aimed to investigate the simultaneous effects of calcium fluoride nanoparticles (CaF2 NPs) and lactobacillus reuteri ATCC PTA 6475 (L. reuteri) against osteoporosis in an ovariectomized rat model (OVX). Methods In this study, 18 matured Wistar female rats were randomly assigned into 6 groups, including control, OVX, sham, OVX + L. reuteri, OVX + CaF2 NPs, and OVX + L. reuteri + CaF2 NPs. We used OVX rats to simulate post-menopausal osteoporosis, and the treatments were begun two weeks before OVX and continued for four weeks. All groups’ blood samples were collected, and serum biomarkers (estrogen, calcium, vitamin D3, and alkaline phosphatase (ALP)) were measured. The tibia and Femur lengths of all groups were measured. Histopathological slides of tibia, kidney, and liver tissues were analyzed using the Hematoxylin and Eosin staining method. Results Our results revealed that dietary supplementation of L. reuteri and CaF2 NPs in low doses for 6 weeks did not show adverse effects in kidney and liver tissues. The tibial and femoral lengths of OVX rats as well as the population of osteoblasts and osteocytes and newly generated osteoid in the tibia remarkably increased in the combination therapy group. Moreover, there was a significant increase in serum estrogen levels and a significant decrease in serum calcium and alkaline phosphatase levels in combination treatment groups compared to the OVX groups not receiving the diet. Conclusions Our results suggest the favorable effects of the simultaneous supplementation of L. reuteri and CaF2 NP to reduce post-menopausal bone loss. Graphical abstract

Abstract Background Cuscuta epithymum Murr. (C. epithymum), as an herbal medicine, has played an anti-cancerous role in various studies; however, its possible neuroprotective effects have been neglected. Here, we aimed to investigate the protective effects of C. epithymum seeds crude extract and different fractions on rat glioblastoma cells (C6) in L-glutamate oxidative condition. Methods Initially, the total phenolic content of C. epithymum crude extract and the fractions (all produced by maceration method) was determined. Subsequently, C6 cells were pre-treated with the various concentrations of crude extract and fractions 24 h before L-glutamate exposure. Likewise, C6 cells were treated with the same concentrations of crude extract and fractions 24 h after exposure to L-glutamate. The cell viability and morphology were compared in crude extract and fractions groups, then superoxide dismutase (SODs) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were measured. The flow cytometry test was used to study C. epithymum crude extract's effects on the cell cycle and also to quantify the apoptosis, necrosis, and live cells population in different groups. Results C. epithymum crude extract and fractions (hexanoic, dichloromethanolic, and methanolic) had concentration-dependent cytotoxicity (IC50:126.47, 2101.96, 140.97, and 218.96 µg/ml, respectively). The crude extract and methanolic fraction contained phenolic compounds (55.99 ± 2.795 and 50.80 ± 2.969 mg gallic acid/g extract), while in hexanoic and dichloromethanolic fractions, the phenolic content was undetectable. In the cell viability assay, in comparison to fractions, the crude extract showed a more protective effect against glutamate-induced oxidative condition (P

Abstract Background The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the promising source for neuroregenerative applications that can improve the injured microenvironment of the damaged neural system. They provide neuronal progenitors and neurotrophic, anti-apoptotic and anti-inflammatory factors. In this study, we aimed to comprehensively explore the various neuronal differentiation potentials of PDLSCs for application in neural regeneration therapy. Main text PDLSCs have superior potential to differentiate into various neural-like cells through a dedifferentiation stage followed by differentiation process without need for cell division. Diverse combination of nutritional factors can be used to induce the PDLSCs toward neural lineage. PDLSCs when coupled with biomaterials could have significant implications for neural tissue repair. PDLSCs can be a new clinical research target for Alzheimer's disease treatment, multiple sclerosis and cerebral ischemia. Moreover, PDLSCs have beneficial effects on retinal ganglion cell regeneration and photoreceptor survival. PDLSCs can be a great source for the repair of injured peripheral nerve through the expression of several neural growth factors and differentiation into Schwann cells. Conclusion In conclusion, these cells are an appealing source for utilizing in clinical treatment of the neuropathological disorders. Although significant in vitro and in vivo investigations were carried out in order for neural differentiation evaluation of these cells into diverse types of neurons, more preclinical and clinical studies are needed to elucidate their therapeutic potential for neural diseases.

Abstract Intraoperative radiotherapy (IORT) could abrogate cancer recurrences, but the underlying mechanisms are unclear. To clarify the effects of IORT-induced wound fluid on tumor progression, we treated breast cancer cell lines and human-derived tumor spheroids in 2D and microfluidic cell culture systems, respectively. The viability, migration, and invasion of the cells under treatment of IORT-induced wound fluid (WF-RT) and the cells under surgery-induced wound fluid (WF) were compared. Our findings showed that cell viability was increased in spheroids under both WF treatments, whereas viability of the cell lines depended on the type of cells and incubation times. Both WFs significantly increased sub-G1 and arrested the cells in G0/G1 phases associated with increased P16 and P21 expression levels. The expression level of Caspase 3 in both cell culture systems and for both WF-treated groups was significantly increased. Furthermore, our results revealed that although the migration was increased in both systems of WF-treated cells compared to cell culture media-treated cells, E-cadherin expression was significantly increased only in the WF-RT group. In conclusion, WF-RT could not effectively inhibit tumor progression in an ex vivo tumor-on-chip model. Moreover, our data suggest that a microfluidic system could be a suitable 3D system to mimic in vivo tumor conditions than 2D cell culture.

Introduction UV-C (254-280 nm) and 280-320 nm) UV-B, UV-A (320-390nm) wavelengths are irradiated with three ultraviolet strips and have detrimental effects on the growth of a number of plants. Ultraviolet light is an important non-living factor that can stimulate the production of secondary metabolites, including antioxidant compounds in plants. Ozone depletion and its consequences, including direct UV radiation on the planet and its effects on crops and medicinal plants, are among the topics that have received very little study. Ultraviolet light in nature occurs only at low intensities, but if the inhibitory effect of the ozone layer in the stratosphere is significantly the result of nitrogen and hydrocarbon oxides the weaker the halogen, the higher its amount.Materials and Methods Portulaca oleracea seeds were prepared by Pakan Isfahan Company. The aim of this study was the effect of ultraviolet rays at different levels (UV-C: 0, 100, 200, 300, 400, 500, 600, and 700 nm) on the activity of photosynthetic pigments and biochemical traits of portulaca oleracea in factorial in a completely randomized design with three replications. After transferring the seeds of portulaca oleracea, the healthy and uniform seeds of this plant were sterilized in 15% sodium hypochlorite solution for 154 minutes and then washed thoroughly with distilled water and placed in a petri dish for germination. Moisture was supplied through filter paper soaked in distilled water. The seeds were planted in pots filled with cocopeat and perlite evenly and watered for 20 days with a half-strength Hoagland solution. Plants were grown for 20 days at a temperature of 30 ± 2 ° C and a light period of 8.16 (light / dark, respectively). Plants for one week, every other day, and for 3 minutes each time by two fluorescent lamps with a wavelength of 260 nm exposed to ultraviolet C (at a distance of 30 cm from the UV light source with an intensity of 27 (w / m2) were located. The traits studied in this study included chlorophyll a, chlorophyll b, total chlorophyll, carotenoids, phenol, flavonoids, and antioxidant activity. In this study, the effect of ultraviolet light on the activity of photosynthetic pigments and biochemical traits of portulaca oleracea was investigated factorially in a completely randomized design with three replications.Results and Discussion The results of the mean comparison showed that the UV treatment of chlorophyll a, b, total chlorophyll, carotenoid of portulaca oleracea was reduced compared to the control; However, UV treatment of portulaca oleracea significantly increased phenol, flavonoids, and antioxidants compared to the control. The effect of different doses of ultraviolet rays on phenol and portulaca oleracea antioxidants showed that the UV-C highest and lowest were 700 and 100 nm, respectively. Decreases in carotenoid content can result in either inhibition of pigment synthesis or their breakdown and degradation. The results of this report indicate significant changes in phenols and flavonoids as compounds it absorbed ultraviolet rays compared to control cells.Conclusion It can be said that excessive exposure to radiation may affect chlorophyll levels by inhibiting chlorophyll biosynthesis or accelerating its degradation. Oxygen is an electron receptor in the electron transport system that produces energy from adenosine triphosphate (ATP) in the body. Under certain conditions, oxygen can be converted to a single electron, creating free radicals. When oxygen is converted to a single electron, it is called active oxygen (ROS). These free radicals cause oxidative stress in plants which oxidative stress leads to damage to macromolecules such as DNA, proteins and so on. Environmental stresses, including UV radiation, produce active oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide (O2-), and hydroxyl radicals (OH), which cause oxidative stress and cause damage to cells, such as DNA. And cause the destruction of these compounds. The plant contains compounds that act as active antioxidants and sweep away active oxygen. In the present study, the observed increase in phenols, flavonoids and antioxidants indicates an increase in the production of free radicals under ultraviolet radiation and shows that the production of these radicals is more than the plant's defense capacity and has caused damage to plant biological membranes. In summary, the application of controlled ultraviolet light stress can provide a new alternative strategy to increase the productivity of the portulaca oleracea plant. Modulating UV-C light in agricultural systems is a promising tool to increase crop production.

After severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, coronavirus disease 2019 (COVID-19) is the third coronavirus epidemic that soon turned into a pandemic. This virus causes acute respiratory syndrome in infected people. The mortality rate of SARS-CoV-2 infection will probably rise unless efficient treatments or vaccines are developed. The global funding and medical communities have started performing more than five hundred clinical examinations on a broad spectrum of repurposed drugs to acquire effective treatments. Besides, other novel treatment approaches have also recently emerged, including cellular host-directed therapies. They counteract the unwanted responses of the host immune system that led to the severe pathogenesis of SARS-CoV-2. This brief review focuses on mesenchymal stem cell (MSC) principles in treating the COVID-19. The US clinical trials database and the world health organization database for clinical trials have reported 82 clinical trials (altogether) exploring the effects of MSCs in COVID-19 treatment. MSCs also had better be tried for treating other pathogens worldwide. MSC treatment may have the potential to end the high mortality rate of COVID-19. Besides, it also limits the long-term inability of survivors.

Purpose: Recently, bone tissue engineering as a new strategy is used to repair and replace bone defects due to limitations in allograft and autograft methods. In this regard, we prepared nanofibrous scaffolds composed of polycaprolactone and magnesium oxide nanoparticles using the electrospinning technique for possible bone tissue engineering applications. Methods: The fabricated composites were characterized via scanning electron microscopy imaging of scaffolds and seeded cells, water contact angle, DAPI staining, and MTT assay. Then osteogenic differentiation of adipose-derived mesenchymal stem cells cultured on this composite scaffold was determined by standard osteogenic marker tests, including alkaline phosphatase activity, calcium deposition, and expression of osteogenic differentiation genes in the laboratory conditions. Results: The Scanning electron microscopy analysis demonstrated that the diameter of nanofibers significantly decreased from 1029.25±209.349 µm to 537.83+0.140 nm, with the increase of MgO concentration to 2% (p

Most medical investigations have found a reduced blood level of miR-146a in type 2 diabetes (T2D) patients, suggesting an important role for miR-146a (microRNA-146a) in the etiology of diabetes mellitus (DM) and its consequences. Furthermore, injection of miR-146a mimic has been confirmed to alleviate diabetes mellitus in diabetic animal models. In this line, deregulation of miR-146a expression has been linked to the progression of nephropathy, neuropathy, wound healing, olfactory dysfunction, cardiovascular disorders, and retinopathy in diabetic patients. In this review, besides a comprehensive review of the function of miR-146a in DM, we discussed new findings on type 1 (T1MD) and type 2 (T2DM) diabetes mellitus, highlighting the discrepancies between clinical and preclinical investigations and elucidating the biological pathways regulated through miR-146a in DM-affected tissues.

Intraoperative radiotherapy (IORT) has become a growing therapy for early-stage breast cancer (BC). Some studies claim that wound fluid (seroma), a common consequence of surgical excision in the tumor cavity, can reflect the effects of IORT on cancer inhibition. However, further research by our team and other researchers, such as analysis of seroma composition, affected cell lines, and primary tissues in two-dimensional (2D) and three-dimensional (3D) culture systems, clarified that seroma could not address the questions about IORT effectiveness in the surgical site. In this review, we mention the factors involved in tumor recurrence, direct or indirect effects of IORT on BC, and all the studies associated with BC seroma to attain more information about the impact of IORT-induced seroma to make a better decision to remove or remain after surgery and IORT. Finally, we suggest that seroma studies cannot decipher the mechanisms underlying the effectiveness of IORT in BC patients. The question of whether IORT-seroma has a beneficial effect can only be answered in a trial with a clinical endpoint, which is not even ongoing.

Objective: Breast cancer (BC) still remains an imperative clinical issue, despite advances in the diagnosis, prognosis and treatment modalities of this malignancy. Hence, progress has been made to identify non-invasive, high sensitive and specific biomarkers. Since immune system affects development of breast cancer, peripheral blood mononuclear cells (PBMCs) -a subpopulation of immune cells- can be considered as a promising tool in the field of BC biomarker research. In the current study, we initially attempted to use concept of the present shared biomarkers in solid tumors and systemic immune profile and then evaluate correlation of these biomarkers to clinical use in cancer research. Materials and Methods: In this experimental study, available microarray gene expression datasets of BC as well as the related PBMCs were retrieved and downloaded from the Gene Expression Omnibus (GEO) database, followed by analysis using GEO2R along with affylmGUI, a R-based package, to obtain differentially expressed genes (DEGs). Signature genes from 20 types of cancer were also applied to validate DEGs. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was carried out to assess mRNA level of CCNB2 in PBMC of the BC patients and healthy subjects. Results: DEGs analysis for the transcription profile of BC cells and PBMCs showed two shared targets, CCNB2 and PGK1. Validation with systems biology using reweighted 20 types of cancer signature genes revealed that CCNB2 is the only common target in BC and its related PBMCs, which was further validated by qRT-PCR implying a significant increase in the level of CCNB2 in the BC patients. Conclusion: Results of this study demonstrated that PBMCs are affected by BC cells and CCNB2 may be of value as a diagnostic biomarker for breast cancer. However, verification would require future detailed experimental plans.

Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.

Abstract We aimed to construct a biodegradable transparent scaffold for culturing corneal endothelial cells by incorporating chitosan nanoparticles (CSNPs) into chitosan/polycaprolactone (PCL) membranes. Various ratios of CSNP/PCL were prepared in the presence of constant concentration of chitosan and the films were constructed by solvent casting method. Scaffold properties including transparency, surface wettability, FTIR, and biocompatibility were examined. SEM imaging, H&E staining, and cell count were performed to investigate the HCECs adhesion. The phenotypic maintenance of the cells during culture was investigated by flow cytometry. Transparency and surface wettability improved by increasing the CSNP/PCL ratio. The CSNP/PCL 50/25, which has the lowest WCA, showed comparable transparency with human acellular corneal stroma. The scaffold was not cytotoxic and promoted the HCECs proliferation as evaluated by MTT assay. Cell counting, flow cytometry, SEM, and H&E results showed appropriate attachment of HCECs to the scaffold which formed a compact monolayer. The developed scaffold seems to be suitable for use in corneal endothelial regeneration in terms of transparency and biocompatibility.

Abstract Cancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitable reservoir. There are conflicting opinions about the role of human amniotic membrane/fluid mesenchymal stem cells (hAMSCS/hAFMSCs) in cancer, as some studies demonstrating the anticancer effects of these cells and others suggesting their progressive effects on cancer. This review focuses on recent findings about the role of hAMSCs/hAFMSCs in cancer treatment and summarizes the suppressing as well as promoting effects of these cells on cancer progression and underling mechanisms.

Background and Aim: Detection of early-stage pancreatic cancer (PaC) patients can decrease the mortality rate through surgical resection thanks to a screening approach of high-risk and asymptomatic individuals. Up to 80% of PaC patients are either hyperglycemic or diabetic at the time of diagnosis. Diabetes mellitus (DM) identification as an early manifestation of PaC may lead to detection of this malignancy at early and presymptomatic stages. Therefore, the current study aims to identify common molecular factors between DM and PaC to shed light on a potential screening for DM as a diagnostic approach for PaC. Methods: The study was divided into three steps including dataset selection and identification of key genes, quantitative real-time polymerase chain reaction (qRT-PCR) to validate these genes, and enrichment analysis of their target genes. Results: Using GEO2R analysis, conducted on microarray dataset (GSE15932), SPI1 and Yin Yang 1 (YY1) genes were found to be expressed in peripheral blood mononuclear cells of PaC, DM, and PaC + DM patients. Moreover, qRT-PCR results in validation of microarray data showed a significant increment of these two genes among all patient groups. Furthermore, enrichment analyses of SPI1 and YY1 target genes revealed that they are mainly expressed in hematopoietic cells and associated with immune responses as well as immune signaling pathways. Discussion: We speculate that this study on SPI1 and YY1 genes and their targets can result in a successful strategy to investigate diabetes as a screening step for better management of PaC screening using standard serologic tests.

Coeliac disease (CD) is a chronic autoimmune disease that is characterized by malabsorption in sensitive individuals. CD is triggered by the ingestion of grains containing gluten. CD is concomitant with several other disorders, including dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, various connective tissue disorders, inflammatory bowel disease, and rheumatoid arthritis. The advent of high throughput technologies has provided a massive wealth of data which are processed in various omics scale fields. These approaches have revolutionized the medical research and monitoring of the biological systems. In this regard, omics scaled analyses of CD by Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases have retrieved 2656 CD associated genes. Amongst, 54 genes were assigned by Venn Diagram of the intersection to be shared by these 3 databases for CD. These common genes were subjected to further analysis and screening. The Enrich database, GeneMANIA, Cytoscape, and WebGestalt (WEB-based GEne SeT AnaLysis Toolkit) were employed for functional analysis. These analyses indicated that the obtained genes are mainly involved in the immune system and signalling pathways related to autoimmune diseases. The STAT1, ALB, IL10, IL2, IL4, IL17A, TGFB1, IL1B, IL6, TNF, IFNG hub genes were particularly indicated to have significant roles in CD. Functional analyses of these hub genes by GeneMANIA indicated that they are involved in immune systems regulation. Moreover, 25 out of 54 genes were identified to be seed genes by the WebGestalt database. Gene set analysis with GEO2R tool from Gene Expression Omnibus (GEO) showed that there were 15 significant genes in GSE76168, 29 significant genes in GSE87460, 12 significant genes in GSE87458, 9 significant genes in GSE87457, 3753 significant genes in GSE112102 and 1043 significant genes in GSE102991 with differential expression in coeliac patients compared to controls. The IRF1and STAT1 genes were common between the significant genes from GEO and the 54 CD related genes from three public databases. In the light these results, nine key genes, including IRF1, STAT1, IL17A, TGFB1, ALB, IL10, IL2, IL4, and IL1B, were identified to be associated with CD. These findings could be used to find novel diagnostic biomarkers, understand the pathology of disease, and devise more efficient treatments.

Objectives: Traditional breast cancer treatments have challenges including inefficiency, multidrug resistance, severe side effects, and targeting non-specifically. The development of alternative treatment strategies has attracted a great deal of interest. Using the amniotic membrane has become a promising and convenient new approach for cancer therapy. This study aimed to evaluate the anti-cancer ability of conditioned medium extracted from the human amniotic membrane (hAM-CM) on breast cancer cells. Methods: Conditioned medium was collected after 48 h incubation of hAM in epithelial up manner. MTT, cell cycle, apoptosis, colony formation, and sphere assays were used to determine the impact of hAM-CM on breast cancer cell lines. The effects of hAM-CM on the migration and invasion of breast cancer cells were determined using scratch wound healing and transwell assays, respectively. Results: Based on the results, cell viability was significantly decreased by hAM-CM in a dose-dependent manner. The hAM-CM remarkably induced apoptosis and necrosis of cancer cells. Moreover, cell migration and invasion potential of cancer cells decreased after the hAM-CM treatment. Further, both the number of colonies and their morphologies were affected by the treatment. In the treated group, a significant decrease in the number of colonies along with an obvious change in their morphologies from holoclone shape to a dominant paracolone structure was observed. Conclusion: Our results indicate that the conditioned medium derived from the human amniotic membrane able to inhibit proliferation and metastasis of tumor cells and can be considered a natural and valuable candidate for breast cancer therapy.

Abstract Background Serous carcinoma, the subtype of ovarian cancer has the highest occurrence and mortality in women. Proteomic profiling using mass spectrometry (MS) has been used to detect biomarkers in tissue s obtained from patients with ovarian cancer. Thus, this study aimed at analyzing the interactome (protein-protein interaction (PPI)) and (MS) data to inspect PPI networks in patients with Low grade serous ovarian cancer. Methods For proteome profiling in Low grade serous ovarian cancer, 2DE and mass spectrometry were used. Differentially expressed proteins which had been determined in Low grade serous ovarian cancer and experimental group separately were integrated with PPI data to construct the (QQPPI) networks. Results Six Hub-bottlenecks proteins with significant centrality values, based on centrality parameters of the network (Degree and between), were found including Transgelin (TAGLN), Keratin (KRT14), Single peptide match to actin, cytoplasmic 1(ACTB), apolipoprotein A-I (APOA1), Peroxiredoxin-2 (PRDX2), and Haptoglobin (HP). Discussion This study showed these six proteins were introduced as hub-bottleneck protein. It can be concluded that regulation of gene expression can have a critical role in the pathology of Low-grade serous ovarian cancer.

Due to an error, Dr. Caitlin D’Amico was mistakenly included as author in this article, published in 2020 in Oncology Reviews (DOI: 10.4081/oncol.2020.429 - PMCID: PMC7036708 - PMID: 32153725), and then retracted (DOI: 10.4081/oncol.2020.493 - PMCID: PMC7196932 - PMID: 32391127). The correct authorship appears above.

Introduction: SARS-CoV-2, as a major threat to human health and economy, has brought in uncertain consequences in the early decade of the 21st century. Since no antiviral therapy or effective vaccine against SARS-CoV-2 is currently available, deciphering the possible mechanisms by which the host responds to the virus seems critical, as it may affect the scientific community around the world toward the development of novel therapeutics. Here, we identified the key regulatory molecules modulating the host response to SARS-CoV-2 that affected the transcriptional profiles of respiratory infections in vitro. Materials and Methods: We used the data recently published on the effect of SARS-CoV-2 on two lung cell lines. We selected the shared differentially expressed genes (DEGs) between the two cell lines. To find the key regulatory molecules, we used transcription factors-miRNA-gene interaction databases and analyzed the data using the FANMOD software to detect the crucial regulatory motifs. Cytoscape was then applied to construct the network. We used the KEGG pathway and Gene Ontology (GO) enrichment analysis to predict the probable intermediating biochemical pathways and biological processes. Results: Our data demonstrated that four triangle-shaped (3edge) feed-forward loop motifs (FFLs) played significant roles, and the integrated FFLs subnetwork was constructed. STAT1, IRF9, IRF7, and PRK12 were the genes shared among them. The most important biological processes relating to the effect of the new virus were linked to response to cytokine, innate immune response, and adaptive immune response. Besides, significantly enriched pathways associated with other different viral infections included the nuclear factor κ-light-chain-enhancer of activated B cells (NF-kappa B) signaling pathway, the nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, and the Jak-STAT signaling pathway. Conclusion: Most of the pathways were related to the cytokines storm that may contribute to different levels of lung injury. These regulatory motifs shed light on the transcriptional signature of the respiratory cells and may be responsible for the development of COVID-19 or can also be used as a potential target for further drug therapies or vaccines.

The main role of amniotic membrane (AM), or amnion, is to protect the fetus from drying out and create an appropriate environment for its growth. AM is also a suitable candidate for the treatment of various diseases due to its unique characteristics. In recent years, a new line of research has focused on the anticancer properties of amnion and its potential use in cancer treatment. The in vitro and in vivo studies indicate the anti-proliferative and proapoptotic activities, as well as the angioregulatory and immunomodulatory properties of the amniotic membrane. However, the exact mechanism and molecular basis of these anticancer effects of AM are not fully elucidated. This paper presents an overview of the latest findings and knowledge about the anticancer effects of AM and its underlying molecular mechanisms, which is crucial for the application of amnion in cancer therapy.

Introduction: Reprograming different cell to neuron have been yet remain attractive field in in regenerative medicine, so discovery new methods or improve exist methods could be helpful. In this study, we analysis the transcriptome data of glia and neuron cells to determine the different gene expression in both groups. Then based on this transcriptom data determine the gene chemical interaction to find the most important chemical structure which induce glia cell to neurons. Material and methods: Data extract from transcriptome database related rat cerebral cortex cells generated by RNAseq technique. By comparison neuron against glia cells (astrocyte, oligodenderocyte and microglia) determined different gene expression. In CTD database determined the most important chemical interact with this gene set. Then by using genetrail2 database determined mechanism of gene set associated to chemicals and miRNA enriched. Results: Result determined different chemical with risk factor and protective factor properties related to 500 genes that enriched in neuron in comparison with glia cells. Carbon nanotube is the first important chemicals that interact with 75 genes of 500. Gene ontology analysis determined carbon nanotube effect on genes that induce neurogenesis, neurodevelopment and differentiation. Genetrail2 release the 29 significant miRNAs enriched in gene interacts with carbon nanotube in which miR-34a and miR-449a are the most significant molecules. Network analysis on these genes represents Kit, Gria1, Syt1, Rab3c and Tubb3 have central roles in neurogenesis by carbon nanotube. Conclusion: In sum up, carbon nanotube is the electrical stimulation biomaterial that are biocompatible to induce glia cell to neuron which apply as devise lonely or combination with cell in damage part of neural tissue.

Background: Cystic echinococcosis (CE) is one of the most important parasitic zoonosis in the world. Post-surgery follow up in CE patients is an important non-solved problem up to now. Therefore, the investigations on this problematic issue would be very applicable in the view of CE clinical treatment. Methods: A total of 24 confirmed liver CE patients sera including eight sera before surgery (BS), eight sera three months post-surgery (3MPS), and eight sera six months post-surgery (6MPS) were used in the present study. Proteomics methods including 2DE and LC-MS/MS were performed on the specimens followed by bioinformatics analysis such as Gene Ontology (GO) and Protein-Protein Interaction (PPI) network analysis. Results: A total of 235 proteins were detected of which 12 differentially expressed proteins (DEP) were identified by LC-MS/MS in all sera. The proteins were presented in BS and suppressed after surgery as follows: HPX, SERPINA1, SERPINC1, CP, HBD, and HBA2. Comparisons of the protein expression in sera of patients BS, 3MPS, and 6MPS revealed that GC, IGJ, AHSG, CD5L, FGG, and APOC3 have been overexpressed in 3MPS and 6MPS. PPI network analysis demonstrated that SERPINC1 and AHSG with more connection in the network could be considered as hub proteins and potential prognostic biomarkers in response to surgical treatment of liver CE. Conclusion: Application of proteomics methods on patient’s sera could be used as a novel biomarker tool for following-up liver CE patients. In this regards, proteomics and, application of bioinformatics analysis including GO and PPI showed that SERPINC1, AHSG and HPX are of more value as a potential follow up biomarkers in response to surgical treatment.

Background: The aim of this research was to compare excretory-secretory and somatic extract materials of Fasciola hepatica and F. gigantica to detect protein maps of two species. Methods: Twenty infected livers were collected from sheep in industrial slaughterhouse in Tehran, 2017-2019. Worms were detached from bile ducts, then recognized according to morphologic and morphometric criteria. After three times washing, worms were incubated in RPMI culture media and excretory-secretory products were collected. Worms were crushed and homogenized for preparation of somatic extract. Two Dimensional Electrophoresis gels were accomplished for both excretory-secretory material and somatic extracts. Gels were scanned with densitometer and analyzed with Same Spots software and protein spots were identified with Expasy database. Results: For both excretory-secretory products and somatic extract, protein spots were appeared with two-dimensional electrophoresis technique. Quantitative analysis showed 40 and 28 protein spots for excretory-secretory of F. hepatica and F. gigantica respectively. For somatic extract 19 and 12 protein spots were recognized for F. hepatica and F. gigantica in that order. Conclusion: The rate of expression of some proteins were more in F. hepatica while expression of other proteins was high in F. gigantica. The expression of protease enzyme was higher in F. gigantica than F. hepatica. These data could be considered for biochemical differentiation of Fasciola species and subsequently to design and prepare of antigens for diagnosis/vaccine development.

Despite global research and continuous improvement in therapy, cancer remains a challenging disease globally, substantiating the need for new treatment avenues. Medical gas plasma technology has emerged as a promising approach in oncology in the last years. Several investigations have provided evidence of an antitumor action in vitro and in vivo, including our recent work on plasma-mediated reduction of breast cancer in mice. However, studies of gas plasma exposure on patient-derived tumors with their distinct microenvironment (TME) are scarce. To this end, we here investigated patient-derived breast cancer tissue after gas plasma-treated ex vivo. The tissues were disjoint to pieces smaller than 100 µm, embedded in collagen, and incubated for several days. The viability of the breast cancer tissue clusters and their outgrowth into their gel microenvironment declined with plasma treatment. This was associated with caspase 3-dependent apoptotic cell death, paralleled by an increased expression of the anti-metastatic adhesion molecule epithelial (E)-cadherin. Multiplex chemokine/cytokine analysis revealed a marked decline in the release of the interleukins 6 and 8 (IL-6, IL-8) and monocyte-chemoattractant-protein 1 (MCP) known to promote a cancer-promoting milieu in the TME. In summary, we provide here, for the first time, evidence of a beneficial activity of gas plasma exposure on human patient-derived breast cancer tissue.

The objective of this study was to develop a system-level understanding of acidosis biology. Therefore, the genes expression differences between the normal and acidosis rumen epithelial tissues were first examined using the RNA-seq data in order to understand the molecular mechanisms involved in the disease and then their corresponding metabolic networks constructed. A number of 1074 genes, 978 isoforms, 1049 transcription start sites (TSS), 998 coding DNA sequence (CDS) and 2 promoters were identified being differentially expressed in the rumen tissue between the normal and acidosis samples (p < 0.05). The functional analysis of 627 up-regulated genes revealed their involvement in ion transmembrane transport, filament organization, regulation of cell adhesion, regulation of the actin cytoskeleton, ATP binding, glucose transmembrane transporter activity, carbohydrate binding, growth factor binding and cAMP metabolic process. Additionally, 111 differentially expressed enzymes were identified between the rumen epithelial tissue of the normal and acidosis steers with 46 up-regulated and 65 down-regulated ones in the acidosis group. The pathways and reactions analyses associated with the up-regulated enzymes indicate that most of these enzymes are involved in the fatty acid metabolism, biosynthesis of amino acids, pyruvate and carbon metabolism while most of the down-regulated ones are involved in purine and pyrimidine, vitamin B6 and antibiotics metabolisms. The degree distribution of both metabolic networks follows a power-law one, hence displaying a scale-free property. The top 15 hub metabolites were determined in the acidosis metabolic network with most of them involved in the fatty acid oxidation, VFA biosynthesis, amino acid biogenesis and glutathione metabolism which plays an important role in the stress condition. The limitations of this study were low number of animals and using only epithelial tissue (ventral sac) for RNA-seq.

Introduction: Oral squamous cell carcinoma (OSCC) is the most abundant dysplasia in the oral cavity that aberrant expression of microRNA plays an important role in cancer progression. It is well known that microRNA-21 expression is oncogenes or tumor suppressor factor in malignancy formation of several cancers. In this study used OSCC tissues to investigate the expression of mir-21 in malignancy causes. Material and Methods: OSCC tissues and normal samples were collected from Amir Alam and Taleghani Hospitals as fresh and frozen samples. The Expression level of miR-21 in OSCC and normal tissues were measured by qRT-PCR. To find the targets related mir-21 used databases including TargetScan, GenTrail2, GO and STITCH online websites. Results: MiR-21 found significantly up-regulated in OSCC tissues compared to normal tissues (Fold-change=5.54). Targets of miR-21 derived from the TargetScan and GeneTrail2 analysis determined the most significant biological processes be associated with the epithelialization, differentiation, and morphogenesis. So overexpression of miR-21 could reverse this process and promote the cells to stemness and metastatic state. EGFR and PDCD4, two targets of miR-21, previously have been demonstrated that are important in OSCC invasion, metastasis, and differentiation. In addition study on targets genes to find anticancer drugs enriched CI-1033 as a tyrosine-kinase inhibitor that previously reported for the treatment of cancer. Conclusion: Our findings indicate miR-21 act as oncomiR in OSCC and may be considered as a biomarker for the development of OSCC treatment.