scholarly journals Cell Line Platforms Support Research into Arthropod Immunity

Insects ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 738
Author(s):  
Cynthia L. Goodman ◽  
David S. Kang ◽  
David Stanley
Keyword(s):  
Immune Responses ◽  
Cell Line ◽  
Cell Lines ◽  
Cost Effective ◽  
Future Research ◽  
Innate Immune Responses ◽  
Pathogenic Viruses ◽  
Future Research Directions ◽  
Bacteria And Fungi ◽  
Robust Systems

Innate immune responses are essential to maintaining insect and tick health and are the primary defense against pathogenic viruses, bacteria, and fungi. Cell line research is a powerful method for understanding how invertebrates mount defenses against pathogenic organisms and testing hypotheses on how these responses occur. In particular, immortal arthropod cell lines are valuable tools, providing a tractable, high-throughput, cost-effective, and consistent platform to investigate the mechanisms underpinning insect and tick immune responses. The research results inform the controls of medically and agriculturally important insects and ticks. This review presents several examples of how cell lines have facilitated research into multiple aspects of the invertebrate immune response to pathogens and other foreign agents, as well as comments on possible future research directions in these robust systems.

N-Acetyl Galactosamine Targeting: Paving the Way for Clinical Application of Nucleotide Medicines in Cardiovascular Diseases

2021 ◽  
Author(s):  
Erik A.L. Biessen ◽  
Theo J.C. Van Berkel
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Antisense Oligonucleotides ◽  
Sugar Metabolism ◽  
Innate Immune ◽  
Future Research ◽  
Clinical Use ◽  
Innate Immune Responses ◽  
Chemically Modified ◽  
Intrinsic Capacity

While the promise of oligonucleotide therapeutics, such as (chemically modified) ASO (antisense oligonucleotides) and short interfering RNAs, is undisputed from their introduction onwards, their unfavorable pharmacokinetics and intrinsic capacity to mobilize innate immune responses, were limiting widespread clinical use. However, these major setbacks have been tackled by breakthroughs in chemistry, stability and delivery. When aiming an intervention hepatic targets, such as lipid and sugar metabolism, coagulation, not to mention cancer and virus infection, introduction of N-acetylgalactosamine aided targeting technology has advanced the field profoundly and by now a dozen of N-acetylgalactosamine therapeutics for these indications have been approved for clinical use or have progressed to clinical trial stage 2 to 3 testing. This technology, in combination with major advances in oligonucleotide stability allows safe and durable intervention in targets that were previously deemed undruggable, such as Lp(a) and PCSK9, at high efficacy and specificity, often with as little as 2 doses per year. Their successful use even the most visionary would not have predicted 2 decades ago. Here, we will review the evolution of N-acetylgalactosamine technology. We shall outline their fundamental design principles and merits, and their application for the delivery of oligonucleotide therapeutics to the liver. Finally, we will discuss the perspectives of N-acetylgalactosamine technology and propose directions for future research in receptor targeted delivery of these gene medicines.

scholarly journals A Customisable Cell Line Model of Glioblastoma

2021 ◽  
Author(s):  
◽  
Devlin Forsythe
Keyword(s):  
Metabolic Rate ◽  
Cell Line ◽  
Cell Lines ◽  
Survival Rates ◽  
Future Research ◽  
Line Model ◽  
Malignant Brain Tumour ◽  
Cell Line Model ◽  
Prognosis Research ◽  
Transplantation Model

<p><b>Glioblastoma is an extremely malignant brain tumour with one of the lowest survival rates of all cancers. Current treatments do very little to alter this prognosis. Research into new therapies and the biology of glioblastoma has made scarce progress over the past decades. This is partly due to the combination of the tumour’s heterogeneity, and the inability of the current animal models to accurately depict this. This project was a pilot study into the development and characterisation of a novel cell line model of glioblastoma, which could be transplanted into immune competent mice, in order to study the disease.</b></p> <p>An immortalised C57BL/6 astrocyte cell line, with an EGFP transgene, was used as the base to add glioblastoma specific mutations. To produce a ‘classical-like’ glioblastoma model, a knockout in Pten was induced, onto which two separate lines the human oncogenes, EGFRVIII and RAS V12, were stably expressed. ‘Secondary-like’ models were created with a knockout of P53, and the stable transfection of IDH1R132H.</p> <p>The ‘classical-like’ cell lines were assessed for how well they mimicked a classical glioblastoma. The Pten knockout cell line showed an increased proliferative and metabolic rate compared with the astrocytes and a significant increase in clonogenicity. The addition of RAS V12 to the cells showed an increased migratory capacity; and the Pten + EGFRVIII cell line had a tendency towards an increased proliferation. The ‘secondary-like’ cell lines were assessed for their survival-related phenotypes. The P53 cell line showed a decreased proliferative rate, but with an increased metabolic rate and clonogenic ability. The introduction of the IDH1 mutant protein resulted in a decreased rate of G2 arrest in response to ionising radiation.</p> <p>These cell lines recapitulated what is seen in human glioblastoma tumours and show potential as a transplantation model. Future research will investigate the tumorigenicity of these cell lines.</p>

scholarly journals The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps

2021 ◽  
Vol 12 ◽  
Author(s):  
Heidi Makrinioti ◽  
Andrew Bush ◽  
James Gern ◽  
Sebastian Lennox Johnston ◽  
Nikolaos Papadopoulos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Infection ◽  
Respiratory Viruses ◽  
Future Research ◽  
Innate Immune Responses ◽  
Asthmatic Children ◽  
Recurrent Wheeze ◽  
The Relationship

Bronchiolitis is the most common cause of hospitalization in infancy and is associated with a higher risk for the development of childhood asthma. However, not all children hospitalized with bronchiolitis will develop asthma. The mechanisms underlying asthma development following bronchiolitis hospitalization are complex. Immune responses to respiratory viruses may underlie both bronchiolitis severity and long-term sequela (such as asthma). Interferons (IFNs) are important components of innate immune responses to respiratory viruses and could influence both asthma development and asthma exacerbations. However, the nature of the relationship between interferon production and wheezing illnesses is controversial. For example, low peripheral blood IFN responses at birth have been linked with recurrent wheeze and asthma development. In contrast, there is evidence that severe illnesses (e.g., hospitalization for bronchiolitis) are associated with increased IFN responses during acute infection (bronchiolitis hospitalization) and a higher risk for subsequent asthma diagnosis. Furthermore, mechanistic studies suggest that bronchial epithelial cells from asthmatic children have impaired IFN responses to respiratory viruses, which may enable increased viral replication followed by exaggerated secondary IFN responses. This review aims to discuss controversies around the role of IFNs as drivers of susceptibility to asthma development following bronchiolitis hospitalization. Past evidence from both mechanistic and cohort studies are discussed. We will highlight knowledge gaps that can inform future research study design.

Bioremediation of Pesticides under the Influence of Bacteria and Fungi

2015 ◽  
pp. 51-72 ◽  
Author(s):  
Mamta ◽  
Rayavarapu Jaganadha Rao ◽  
Khursheed Ahmad Wani
Keyword(s):  
Scientific Community ◽  
Cost Effective ◽  
Future Research ◽  
Complex Nature ◽  
Potential Threat ◽  
Physical Methods ◽  
Effective Manner ◽  
The Future ◽  
Research Problems ◽  
Bacteria And Fungi

The demand and development of chemicals, pesticides, fertilizers, and pharmaceuticals is increasing constantly posing a potential threat to the environment. The presence of pesticides and their impact makes their removal and detoxification a more urgent need. Bioremediation technologies have been successfully used and are gaining more and more importance with increased acceptance of eco-friendly remediation solutions among the scientific community. Bioremediation by fungi and bacteria is considered a better option for making environment free from pesticides, as chemical and physical methods are not only costly but also not very effective. However, the complex nature of pesticides is an obstacle to degrade the pesticides, so more versatile and robust microorganisms need to be identified which can produce the desired result in a very cost-effective manner. This study examines the role played by fungi and bacteria in degradation of the pesticides in environment and also identify the future research problems in this regard that need to be experimented.

scholarly journals Feasibility of Generating Adeno-Associated Virus Packaging Cell Lines Containing Inducible Adenovirus Helper Genes

2002 ◽  
Vol 76 (4) ◽  
pp. 1904-1913 ◽  
Author(s):  
Chunping Qiao ◽  
Juan Li ◽  
Anna Skold ◽  
Xudong Zhang ◽  
Xiao Xiao
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cost Effective ◽  
Helper Virus ◽  
Vector System ◽  
Wild Type ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Packaging Cell ◽  
Producer Cell

ABSTRACT The adeno-associated virus (AAV) vector system is based on nonpathogenic and helper-virus-dependent parvoviruses. The vector system offers safe, efficient, and long-term in vivo gene transfer in numerous tissues. Clinical trials using AAV vectors have demonstrated vector safety as well as efficiency. The increasing interest in the use of AAV for clinical studies demands large quantities of vectors and hence a need for improvement in vector production. The commonly used transient-transfection method, although versatile and free of adenovirus (Ad), is not cost-effective for large-scale production. While the wild-type-Ad-dependent AAV producer cell lines seem to be cost-effective, this method faces the problem of wild-type Ad contamination. To overcome these shortcomings, we have explored the feasibility of creating inducible AAV packaging cell lines that require neither transfection nor helper virus infection. As a first step toward that goal, we have created a cell line containing highly inducible Ad E1A and E1B genes, which are essential for AAV production. Subsequently, the AAV Rep and Cap genes and an AAV vector containing a green fluorescent protein (GFP) reporter gene were stably introduced into the E1A-E1B cell line, generating inducible AAV-GFP packaging cell lines. Upon induction of E1A and E1B genes and infection with replication-defective Ad with E1A, E1B, and E3 deleted, the packaging cells yielded high-titer AAV-GFP vectors. Finally, the E2, E4, and VA genes of Ad, under the control of their endogenous promoters, were also introduced into these cells. A few producer cell lines were obtained, which could produce AAV-GFP vectors upon simple drug induction. Although future improvement is necessary to increase the stability and vector yield of the cells, our study has nonetheless demonstrated the feasibility of generating helper-virus-free inducible AAV producer cell lines.

scholarly journals A Blueprint for Cancer-Related Inflammation and Host Innate Immunity

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3211
Author(s):  
Lucia García-López ◽  
Isabel Adrados ◽  
Dolors Ferres-Marco ◽  
Maria Dominguez
Keyword(s):  
Drosophila Melanogaster ◽  
Immune Responses ◽  
Gene Networks ◽  
Cost Effective ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Host Interactions ◽  
Powerful Means ◽  
Adult Drosophila

Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer–host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events—a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.

scholarly journals Myeloma cell line–derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3880-3889 ◽  
Author(s):  
Jianfei Qian ◽  
Sungyoul Hong ◽  
Siqing Wang ◽  
Liang Zhang ◽  
Luhong Sun ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Immune Responses ◽  
Cell Line ◽  
Cell Lines ◽  
Tumor Antigens ◽  
Myeloma Cell ◽  
Myeloma Cell Line ◽  
Custom Made ◽  
Shock Proteins

Abstract Tumor cell–derived heat shock proteins are used as vaccines for immunotherapy of cancer patients. However, current approaches require the generation of custom-made products and are clinically ineffective. To improve the applicability of heat shock protein–based immunotherapy in cancers and to enhance clinical efficacy, we explored combinational treatments in a myeloma setting using pooled heterogeneous or allogeneic myeloma cell line–derived glycoprotein 96 (gp96) as universal vaccines, and clearly demonstrated that pooled but not single gp96 from heterogeneous or allogeneic myeloma cell lines was as effective as autologous gp96 in protecting mice from tumor challenge and rechallenge and in treating established myeloma. We showed that interferon γ and CD4+ and CD8+ T cells were required for gp96-induced antimyeloma responses and that pooled gp96 induced broader immune responses that protected mice from developing different myeloma. Furthermore, pooled gp96 plus CpG in combination with anti-B7H1 or anti–interleukin-10 monoclonal antibodies were effective in treating mice with large tumor burdens. Thus, this study strongly suggests that pooled gp96 vaccines from myeloma cell lines can replace gp96 vaccines from autologous tumors for immunotherapy and induce immune responses against broader tumor antigens that may protect against tumor recurrence and development of unrelated tumors in vaccinated myeloma patients.

scholarly journals Vpx enhances innate immune responses independently of SAMHD1 during HIV-1 infection

Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Oya Cingöz ◽  
Nicolas D. Arnow ◽  
Mireia Puig Torrents ◽  
Norbert Bannert
Keyword(s):  
Immune Responses ◽  
Cell Lines ◽  
Myeloid Cells ◽  
Adaptor Protein ◽  
Myeloid Cell ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Accessory Gene ◽  
Monocytic Cell ◽  
Hiv 1

Abstract Background The genomes of HIV-2 and some SIV strains contain the accessory gene vpx, which carries out several functions during infection, including the downregulation of SAMHD1. Vpx is also commonly used in experiments to increase HIV-1 infection efficiency in myeloid cells, particularly in studies that investigate the activation of antiviral pathways. However, the potential effects of Vpx on cellular innate immune signaling is not completely understood. We investigated whether and how Vpx affects ISG responses in monocytic cell lines and MDMs during HIV-1 infection. Results HIV-1 infection at excessively high virus doses can induce ISG activation, although at the expense of high levels of cell death. At equal infection levels, the ISG response is potentiated by the presence of Vpx and requires the initiation of reverse transcription. The interaction of Vpx with the DCAF1 adaptor protein is important for the enhanced response, implicating Vpx-mediated degradation of a host factor. Cells lacking SAMHD1 show similarly augmented responses, suggesting an effect that is independent of SAMHD1 degradation. Overcoming SAMHD1 restriction in MDMs to reach equal infection levels with viruses containing and lacking Vpx reveals a novel function of Vpx in elevating innate immune responses. Conclusions Vpx likely has as yet undefined roles in infected cells. Our results demonstrate that Vpx enhances ISG responses in myeloid cell lines and primary cells independently of its ability to degrade SAMHD1. These findings have implications for innate immunity studies in myeloid cells that use Vpx delivery with HIV-1 infection.

scholarly journals Comparison of in vitro (fish cell line) and in vivo (fish and crustacean) acute toxicity tests in aquatic toxicology

2021 ◽  
Author(s):  
J Kolarova ◽  
J Velisek ◽  
Z Svobodova
Keyword(s):  
Acute Toxicity ◽  
Cell Line ◽  
Cell Lines ◽  
Poecilia Reticulata ◽  
Cost Effective ◽  
Neutral Red ◽  
Toxicity Tests ◽  
Fish Cell

The use of in vitro (fish cell lines) is a cost-effective, very rapid, and informative tool for toxicological assessments. Using the neutral red (NR) assay, we compared the in vitro acute toxicity (20hEC50) of twenty-six chemical substances on a rainbow trout gonad cell line (RTG-2) with their in vivo acute toxicity to Barbados Millions Poecilia reticulata (48hLC50, OECD 203) and crustacean Daphnia magna (48hEC50, OECD 202). The 20hEC50 values obtained by the NR assay were higher in nearly all the cases when compared to the 48hLC50 in P. reticulata and the 48hEC50 in D. magna, indicating that the sensitivity of the RTG-2 cell line was lower compared to P. reticulata and D. magna. A high (r = 0.89) and significant (P &lt; 0.001) correlation was recorded between the 20hEC50 values of the RTG-2 and the 48hEC50 values of D. magna. The correlation between the 20hEC50 values of the RTG-2 and the 48hLC50 values of P. reticulata was lower (r = 0.65; P &lt; 0.001), but also significant. The authors recommend use of the NR assay on the RTG-2 cell lines as a screening protocol to evaluate the toxicity of xenobiotics in aquatic environments to narrow the spectrum of the concentrations for the fish toxicity test.

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