An Experimental Investigation of Ultraweak Photon Emission from Adult Murine Neural Stem Cells

Neurons like other living cells may have ultraweak photon emission (UPE) during neuronal activity. This study is aimed to evaluate UPE from neural stem cells (NSC) during their serial passaging and differentiation. We also investigate whether the addition of silver nanoparticles (AgNPs) or enhancement of UPE (by AgNPs or mirror) affect the differentiation of NSC. In our method, neural stem and progenitor cells of subventricular zone (SVZ) are isolated and expanded using the neurosphere assay. The obtained dissociated cells allocated and cultivated into three groups: groups: I: cell (control), II: cell + mirror, and III: cell + AgNPs. After seven days, the primary neurospheres were counted and their mean number was obtained. Serial passages continuous up to sixth passages in the control group. Differentiation capacity of the resulting neurospheres were evaluated in vitro by immunocytochemistry techniques. Measurement of UPE was carried out by photomultiplier tube (PMT) in the following steps: at the end of primary culture, six serial cell passages of the control group, before and after of the differentiation for 5 minutes. The results show that neither mirror nor AgNPs affect on the neurosphere number. The UPE of the NSC in the sixth subculturing passage was significantly higher than in the primary passage (P < 0.05). AgNPs significantly increased the UPE of the NSC compared to the control group before and after the differentiation (P < 0.05). Also, the treatment with AgNPs increased 44% neuronal differentiation of the harvested NSCs. UPE of NSC after the differentiation was significantly lower than that before the differentiation in each groups, which is in appropriate to the cell numbers (P < 0.0001). The mirror did not significantly increase UPE, neither before nor after the differentiation of NSC. As a conclusion, NSC have UPE-properties and the intensity is increased by serial passaging that are significant in the sixth passage. The AgNPs increases the UPE intensity of NSC that pushes more differentiation of NSC to the neurons. The mirror was not effective in enhancement of UPE. As a result, UPE measurement may be suitable for assessing and studying the effects of nanoparticles in living cells and neurons.This work was supported by grant No. 94-01-01-10157 from Shiraz University of Medical Sciences, Shiraz, Iran. This article was a part of the thesis written by Esmaeil Fereydoni, MSc. student of Anatomy

Studies examining the efficacy of therapeutically enhanced human mast cells as a cancer immunotherapy

The emergence of cancer immunotherapies utilizing adoptive cell transfer (ACT) continues to be one of the most promising strategies for cancer treatment. Mast cells (MCs), ubiquitous tissue cells most commonly associated with Type I hypersensitivity, bind immunoglobin E (IgE) with high affinity, produce anti-cancer agents such as tumor necrosis factor alpha (TNF-?) and granulocyte macrophage colony-stimulating factor (GM-CSF), and populate practically all tumor microenvironments. Yet, the role of MCs in cancer pathologies remains controversial as direct evidence for anti-tumor or pro-tumor effects are lacking. Here we initially present an improved method for obtaining a large number of human MCs from adipose tissue. The proposed method has several advantages over current methods and can serve as a new source of human MCs for more realistic studies on the biology of this cell type in humans. Then, we found that HER2/neu tumor-specific IgE-sensitized MCs bound, penetrated, and killed HER2/neu-positive tumor masses in vitro. Further in solid tumor human breast cancer (BC) xenograft mouse models, infusion of HER2/neu IgE-sensitized human adipose-derived mast cells (ADMC) co-localized to BC cells, decreased tumor burden, and prolonged overall survival without signs of toxicity. These studies suggest MCs can be polarized from Type I hypersensitivity-mediating cells to tumor-attacking cells and may provide further options for cancer therapeutics for which tumor targeted IgEs are available. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]]]> 2021 Cancer $x Immunotherapy Tumors$x Immunological aspects Mast cells $x Immunology English http://libres.uncg.edu/ir/uncg/f/Fereydouni_uncg_0154D_13412.pdf oai:libres.uncg.edu/37049 2022-01-31T16:51:48Z UNCG An application of fixed vs. growth mindset to music performance Gray, Kirsten J. NC DOCKS at The University of North Carolina at Greensboro <![CDATA[This document applies the concept of a fixed vs. growth mindset to music performance in order to promote awareness among classical musicians. As first outlined by Carol S. Dweck, a person with a fixed mindset holds the beliefs that their qualities and abilities are innate and unchangeable. In contrast, a person with a growth mindset believes that one can cultivate their abilities and qualities through effort, strategy, and help from others. This document consists of a review of psychological studies and reflects on how musicians with fixed vs. growth mindsets might respond to internal dialogue, external feedback, and personal setbacks

Harnessing the Anti-Tumor Mediators in Mast Cells as a New Strategy for Adoptive Cell Transfer for Cancer

The emergence of cancer immunotherapies utilizing adoptive cell transfer (ACT) continues to be one of the most promising strategies for cancer treatment. Mast cells (MCs) which occur throughout vascularized tissues, are most commonly associated with Type I hypersensitivity, bind immunoglobin E (IgE) with high affinity, produce anti-cancer mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte macrophage colony-stimulating factor (GM-CSF), and generally populate the tumor microenvironments. Yet, the role of MCs in cancer pathologies remains controversial with evidence for both anti-tumor and pro-tumor effects. Here, we review the studies examining the role of MCs in multiple forms of cancer, provide an alternative, MC-based hypothesis underlying the mechanism of therapeutic tumor IgE efficacy in clinical trials, and propose a novel strategy for using tumor-targeted, IgE-sensitized MCs as a platform for developing new cellular cancer immunotherapies. This autologous MC cancer immunotherapy could have several advantages over current cell-based cancer immunotherapies and provide new mechanistic strategies for cancer therapeutics alone or in combination with current approaches

Association of rs1042522 SNP with Clinicopathologic Factors of Breast Cancer Patients in the Markazi Province of Iran

BACKGROUND: The nucleotide changes in different genetic loci increased the incidence risk of breast cancer. AIM: The aim of present study was to investigate genotype distribution at codon 72 of the TP53 gene (rs1042522) in breast cancer patients to achieve a potential diagnostic marker related to some demographic feathers. METHODS: In our case-control study, blood samples were collected from a total of 34 patients harboured breast cancer. DNA was extracted, and nested-PCR was performed. Products were digested with AccII and subsequently were sequenced. Results were compared with samples characteristics. RESULTS: The PCR results indicated the correct implementation of extraction and amplification protocol. The genotypic distribution at codon 72 of TP53 in control group was 20%, 62.4% and 16.6% for Arg (wildtype), Arg/Pro (heterozygous) and Pro (homozygous variant) respectively. Also, this distribution in the patient group was 23.52% homozygous, 50% heterozygous, and 26.47% another homozygous variant (Adjusted odds ratio: 1.12 and 95%CI = 0.57 to 2.2, P = 0.03). The absence of Arg at codon 72 of TP53 is relevant with age higher than 40 years and metastasis to other organs. CONCLUSION: Polymorphism at codon 72 of TP53 was associated with high-grades of breast cancer risk and different responses to chemotherapy treatment. It is recommended genotype distribution of codon 72 of TP53 before chemotherapy

Human Tumor Targeted Cytotoxic Mast Cells for Cancer Immunotherapy

The diversity of autologous cells being used and investigated for cancer therapy continues to increase. Mast cells (MCs) are tissue cells that contain a unique set of anti-cancer mediators and are found in and around tumors. We sought to exploit the anti-tumor mediators in MC granules to selectively target them to tumor cells using tumor specific immunoglobin E (IgE) and controllably trigger release of anti-tumor mediators upon tumor cell engagement. We used a human HER2/neu-specific IgE to arm human MCs through the high affinity IgE receptor (FcεRI). The ability of MCs to bind to and induce apoptosis of HER2/neu-positive cancer cells in vitro and in vivo was assessed. The interactions between MCs and cancer cells were investigated in real time using confocal microscopy. The mechanism of action using cytotoxic MCs was examined using gene array profiling. Genetically manipulating autologous MC to assess the effects of MC-specific mediators have on apoptosis of tumor cells was developed using siRNA. We found that HER2/neu tumor-specific IgE-sensitized MCs bound, penetrated, and killed HER2/neu-positive tumor masses in vitro. Tunneling nanotubes formed between MCs and tumor cells are described that parallel tumor cell apoptosis. In solid tumor, human breast cancer (BC) xenograft mouse models, infusion of HER2/neu IgE-sensitized human MCs co-localized to BC cells, decreased tumor burden, and prolonged overall survival without indications of toxicity. Gene microarray of tumor cells suggests a dependence on TNF and TGFβ signaling pathways leading to apoptosis. Knocking down MC-released tryptase did not affect apoptosis of cancer cells. These studies suggest MCs can be polarized from Type I hypersensitivity-mediating cells to cytotoxic cells that selectively target tumor cells and specifically triggered to release anti-tumor mediators. A strategy to investigate which MC mediators are responsible for the observed tumor killing is described so that rational decisions can be made in the future when selecting which mediators to target for deletion or those that could further polarize them to cytotoxic MC by adding other known anti-tumor agents. Using autologous human MC may provide further options for cancer therapeutics that offers a unique anti-cancer mechanism of action using tumor targeted IgE’s

Human Mast Cells From Adipose Tissue Target and Induce Apoptosis of Breast Cancer Cells

Mast cells (MC) are important immune sentinels found in most tissue and widely recognized for their role as mediators of Type I hypersensitivity. However, they also secrete anti-cancer mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study was to investigate adipose tissue as a new source of MC in quantities that could be used to study MC biology focusing on their ability to bind to and kill breast cancer cells. We tested several cell culture media previously demonstrated to induce MC differentiation. We report here the generation of functional human MC from adipose tissue. The adipose-derived mast cells (ADMC) are phenotypically and functionally similar to connective tissue expressing tryptase, chymase, c-kit, and FcεRI and capable of degranulating after cross-linking of FcεRI. The ADMC, sensitized with anti-HER2/neu IgE antibodies with human constant regions (trastuzumab IgE and/or C6MH3-B1 IgE), bound to and released MC mediators when incubated with HER2/neu-positive human breast cancer cells (SK-BR-3 and BT-474). Importantly, the HER2/neu IgE-sensitized ADMC induced breast cancer cell (SK-BR-3) death through apoptosis. Breast cancer cell apoptosis was observed after the addition of cell-free supernatants containing mediators released from FcεRI-challenged ADMC. Apoptosis was significantly reduced when TNF-α blocking antibodies were added to the media. Adipose tissue represents a source MC that could be used for multiple research purposes and potentially as a cell-mediated cancer immunotherapy through the expansion of autologous (or allogeneic) MC that can be targeted to tumors through IgE antibodies recognizing tumor specific antigens

Cavernous sinus thrombosis syndrome and brainstem involvement in patient with leptospirosis: Two rare complications of leptospirosis

Leptospirosis is a bacterial disease that is caused by pathogenic spirochetes of the genus Leptospira. It can affect humans and animals. In humans, it can lead to a wide spectrum of symptoms. It is known as the most common zoonosis in the world. The typical presentation of the disease is an acute biphasic febrile illness with or without jaundice. Less common clinical manifestations may result from involvement of different human body systems. In many places, this disease may be under-diagnosed, especially when associated with neurological complications. Moreover, without treatment, leptospirosis can lead to organ damages, and even death. Neurological complications are uncommon and are reported in a few cases. Cavernous sinus thrombosis syndrome and brainstem involvement are rare complications of leptospirosis and are associated with a high mortality risk. To our knowledge, no such cases have been reported in the literature

Identification and Characterization of Tunneling Nanotubes Involved in Human Mast Cell FcεRI-Mediated Apoptosis of Cancer Cells

Mast cells (MCs) are found in practically all tissues where they participate in innate and adaptive immune responses. They are also found in and around tumors, yet their interactions with cancer cells and the resulting impact on cancer cell growth and metastasis are not well understood. In this study, we examined a novel mechanism of IgE-FcεRI-mediated, intercellular communication between human adipose-derived mast cells (ADMC) and cancer cells. The formation of heterotypic tunneling nanotubes (TnT) and membrane structures between MCs and tumor cells in vitro was examined using microscopy and a diverse array of molecule-specific indicator dyes. We show that several MC-specific structures are dependent on the specific interactions between human tumor IgE-sensitized MCs and antigens on the tumor cell surface. The formation of TnT, membrane blebs and other MC-specific structures paralleled FcεRI-degranulation occurring within 30 min and persisting for up to 24 h. The TnT-specific adhesion of FcεRI-activated MCs to tumor cells was characterized by the transport of the MC granule content into the tumor cells, including tryptase and TNF-α. This interaction led to apoptosis of the tumor cells, which differs from previous studies examining tissue cells within the cancer microenvironment. The formation of heterotypic TnT results in stimulation of an invasive tumor cell phenotype and increased tumor cell invasion and chemoresistance of the cancer cells. These studies describe a heretofore-unrecognized mechanism underlying IgE-mediated interactions and FcεRI-activated MC-mediated killing of tumor cells through the formation of TnT

Efficacy of Synbiotics for Treatment of Bacillary Dysentery in Children: A Double-Blind, Randomized, Placebo-Controlled Study

Bacillary dysentery is a major cause of children’s admission to hospitals. To assess the probiotic and prebiotic (synbiotics) effects in children with dysentery in a randomized clinical trial, 200 children with dysentery were studied in 2 groups: the synbiotic group received 1 tablet/day of synbiotic for 3–5 days and the placebo group received placebo tablets (identical tablet form like probiotics). The standard treatment was administered for all patients. Duration of hospitalization, dysentery, fever, and the weight loss were assessed in each group. It was concluded that there was no significant difference in both groups in the baseline characteristics. The mean duration of dysentery reduced (P<0.05). The mean duration of fever has been significantly reduced in the synbiotic group (1.64±0.87 days) in comparison to the placebo group (2.13±0.94 days) (P<0.001). Average amount of weight loss was significantly lower in the synbiotic group in comparison to that in the placebo group (129.5±23.388 grams and 278±28.385 grams, resp.; P<0.001). There was no significant difference in the mean duration of hospitalization in both groups (P>0.05). The use of synbiotics as an adjuvant therapy to the standard treatment of dysentery significantly reduces the duration of dysentery, fever, and rate of weight losses. The trial is registered with IRCT201109267647N1

Is there any association between Serum anti-HSP27 antibody level and the presence of metabolic syndrome; population based case-control study

Background: Heat shock protein 27 (HSP27) is an intracellular chaperone constitutively expressed in many cell types including cardio myocytes and endothelial cells. Circulating levels of HSP27 and anti-HSP27 antibody are higher in patients with CVD. Anti-HSP27 antibody concentrations were also reported to be increased in atherogenesis. We aimed to evaluate serum anti-HSP27 antibody titers in individuals with, or without, MetS in the MASHAD study cohort with large sample size in 6,568 subjects