scholarly journals Designing and Immunomodulating Multiresponsive Nanomaterial for Cancer Theranostics

2021 ◽  
Vol 8 ◽  
Author(s):  
Amreen Khan ◽  
Faith Dias ◽  
Suditi Neekhra ◽  
Barkha Singh ◽  
Rohit Srivastava
Keyword(s):  
Immune Response ◽  
Vital Role ◽  
Current Status ◽  
Therapeutic Window ◽  
Host Immune System ◽  
Disease Heterogeneity ◽  
New Approach ◽  
Diagnostic Agents ◽  
Cancer Theranostics

Cancer has been widely investigated yet limited in its manifestation. Cancer treatment holds innovative and futuristic strategies considering high disease heterogeneity. Chemotherapy, radiotherapy and surgery are the most explored pillars; however optimal therapeutic window and patient compliance recruit constraints. Recently evolved immunotherapy demonstrates a vital role of the host immune system to prevent metastasis recurrence, still undesirable clinical response and autoimmune adverse effects remain unresolved. Overcoming these challenges, tunable biomaterials could effectively control the co-delivery of anticancer drugs and immunomodulators. Current status demands a potentially new approach for minimally invasive, synergistic, and combinatorial nano-biomaterial assisted targeted immune-based treatment including therapeutics, diagnosis and imaging. This review discusses the latest findings of engineering biomaterial with immunomodulating properties and implementing novel developments in designing versatile nanosystems for cancer theranostics. We explore the functionalization of nanoparticle for delivering antitumor therapeutic and diagnostic agents promoting immune response. Through understanding the efficacy of delivery system, we have enlightened the applicability of nanomaterials as immunomodulatory nanomedicine further advancing to preclinical and clinical trials. Future and present ongoing improvements in engineering biomaterial could result in generating better insight to deal with cancer through easily accessible immunological interventions.

scholarly journals Recent Progress in Lipid Nanoparticles for Cancer Theranostics: Opportunity and Challenges

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 840
Author(s):  
Sarah I. Bukhari ◽  
Syed Sarim Imam ◽  
Mohammad Zaki Ahmad ◽  
Parameswara Rao Vuddanda ◽  
Sultan Alshehri ◽  
...  
Keyword(s):  
Drug Loading ◽  
Drug Distribution ◽  
Multi Drug Resistance ◽  
Host Immune System ◽  
System A ◽  
Conventional Drug ◽  
Diagnostic Agents ◽  
Causes Of Mortality ◽  
Cancer Theranostics ◽  
Poor Efficacy

Cancer is one of the major leading causes of mortality in the world. The implication of nanotherapeutics in cancer has garnered splendid attention owing to their capability to efficiently address various difficulties associated with conventional drug delivery systems such as non-specific biodistribution, poor efficacy, and the possibility of occurrence of multi-drug resistance. Amongst a plethora of nanocarriers for drugs, this review emphasized lipidic nanocarrier systems for delivering anticancer therapeutics because of their biocompatibility, safety, high drug loading and capability to simultaneously carrying imaging agent and ligands as well. Furthermore, to date, the lack of interaction between diagnosis and treatment has hampered the efforts of the nanotherapeutic approach alone to deal with cancer effectively. Therefore, a novel paradigm with concomitant imaging (with contrasting agents), targeting (with biomarkers), and anticancer agent being delivered in one lipidic nanocarrier system (as cancer theranostics) seems to be very promising in overcoming various hurdles in effective cancer treatment. The major obstacles that are supposed to be addressed by employing lipidic theranostic nanomedicine include nanomedicine reach to tumor cells, drug internalization in cancer cells for therapeutic intervention, off-site drug distribution, and uptake via the host immune system. A comprehensive account of recent research updates in the field of lipidic nanocarrier loaded with therapeutic and diagnostic agents is covered in the present article. Nevertheless, there are notable hurdles in the clinical translation of the lipidic theranostic nanomedicines, which are also highlighted in the present review along with plausible countermeasures.

scholarly journals The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response

2016 ◽  
Vol 84 (12) ◽  
pp. 3458-3470 ◽  
Author(s):  
Mike Khan ◽  
Jerome S. Harms ◽  
Fernanda M. Marim ◽  
Leah Armon ◽  
Cherisse L. Hall ◽  
...  
Keyword(s):  
Immune Response ◽  
Second Messenger ◽  
Host Immune Response ◽  
Vital Role ◽  
Host Cells ◽  
Content Type ◽  
Type Iv

Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host- Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a Δ bpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the Δ bpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase Δ cgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, Δ bpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection.

scholarly journals Formal modeling of the key determinants of Hepatitis C Virus (HCV) induced adaptive immune response network: An integrative approach to map the cellular and cytokine-mediated host immune regulations

2018 ◽  
Author(s):  
Ayesha Obaid ◽  
Anam Naz ◽  
Shifa Tariq Ashraf ◽  
Faryal Mehwish Awan ◽  
Aqsa Ikram ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Biological Data ◽  
Signaling Networks ◽  
Host Immune System ◽  
Adaptive Immune ◽  
Ifn Γ

Background. Hepatitis C Virus (HCV) is a major causative agent of liver infection leading to critical liver damage. In response to HCV, the improper regulation of host immune system leads to chronic infection. The host immune system employs multiple cell types, diverse variety of cytokine mediators and interacting signaling networks to neutralize the HCV infection. To understand the complexity of the interactions within the immune signaling networks, systems biology provides an efficient alternative approach. Integrating such approaches with immunology and virology helps to study highly complex immune regulatory networks within the host and presents a concise view of the whole system. Methods. Initially, a logic-based diagram is generated based on multiple reported interactions between immune cells and cytokines during host immune response to HCV. Furthermore, an abstracted sub-network is modeled qualitatively which consists of both the key cellular and cytokine components of the HCV induced immune system. Rene’ Thomas formalism is applied in the study to generate a qualitative model which requires only the qualitative thresholds and associated logical parameters generated via SMBioNet software in accordance with biological observations. Furthermore, the continuous dynamics of the model have been studied via Petri nets based analysis. Results. In the presence of NS5A protein of HCV, the behaviors of the Natural Killer (NK) and T regulatory (Tregs) cells along with cytokines such as IFN-γ, IL-10, IL-12 are predicted. The model also attempts to consider the viral strategies to circumvent immune response mediated by viral proteins. The state graph analysis enabled the prediction of paths leading to disease state. The most probable cycle is predicted based on maximum betweenness centrality. Furthermore, to study the continuous dynamics of the modeled network, a Petri net (PN) model was generated. The predictive ability of the model implicates the critical role of IL-12 over-expression in pathogenesis. This observation speculates that IL-12 has a dual role under varying circumstances and leads to varying disease outcomes. Conclusion. This model attempts to reduce the noisy biological data and captures a holistic view of the regulations amongst the key determinants of HCV induced adaptive immune responses. The observations warrant for further studies to elucidate the role of IL-12 under varying external and internal stimuli. Also, introducing diversion by therapeutic perturbation may divert the system from diseased paths to recovery by stabilizing the activation of IFN-γ producing NK cells. The modeling approach employed in this study can be extended to include real-time experimental data to propose new therapeutic interventions.

scholarly journals Mechanism of IL-10 Protective Effect in Development of Childhood B Cell Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4075-4075
Author(s):  
Briana Fitch ◽  
Michelle L. Hermiston ◽  
Joseph L. Wiemels ◽  
Scott C. Kogan
Keyword(s):  
Immune Response ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Model ◽  
B Cell ◽  
Knockout Mice ◽  
Lymphoblastic Leukemia ◽  
Host Immune System ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. While significant progress has been made in the treatment of B-ALL, the factors that influence the development of B-ALL remain poorly understood. Epidemiological studies have established a role of early childhood infections in altering leukemia risk. The focus of these studies has been on documenting the number and timing of infectious exposures; however, the role of host immune response to infections in B-ALL development is largely unknown. Low birth levels of the immunomodulatory cytokine interleukin 10 (IL-10) are associated with a 25 fold increased risk of developing childhood B-ALL. Mechanistically, IL-10 plays a critical role in controlling the neonatal immune response to infections. Together, these findings suggest that IL-10, an important regulator of host immune responsiveness, protects against childhood B-ALL. To establish whether loss of IL-10 has an impact on leukemogenesis, we crossed Il10 knockout mice to the TEL-AML1 (ETVX6-RUNX1I) Ckdn2anull mouse model of childhood B-ALL. ETV6-RUNX1 t(12;21) is the most frequent chromosomal translocation in childhood B-ALLand one-fourth of these leukemias are observed in combination with loss of the Cdkn2a locus. The leukemia incidence in TEL-AML1 Ckdn2anull mice is 60%, therefore this is a robust and clinically relevant mouse model of childhood B-ALL. We used this model to assess the role of IL-10 in leukemogenesis by following Il10 knockout TEL-AML1 Ckdn2anull mice for the development of disease in comparison with control IL-10 expressing TEL-AML1 Ckdn2anull mice. We found that Il10 knockout accelerated leukemogenesis in the presence of TEL-AML1. The cancer free survival of the IL-10 expressing TEL-AML1 Ckdn2anull mice (n=74) was 227 days, whereas the survival of IL-10 knockout mice (n=40) was reduced to 180 days (p<0.0005). These data support a causal role of low levels of IL-10 in the development of B-ALL and raise the possibility of using an IL-10 receptor agonist for leukemia prevention in children with high risk of B-ALL. Thus, IL-10 loss is a defect in the host immune system that accelerates childhood B-ALL development, potentially through modifying immune responses to infections. Studies to understand the mechanism of how low IL-10 levels interact with infections to influence leukemogenesis are underway. Disclosures No relevant conflicts of interest to declare.

scholarly journals Harnessing immunological targets for COVID-19 immunotherapy

2021 ◽  
Author(s):  
Abhishesh Kumar Mehata ◽  
Matte Kasi Viswanadh ◽  
Vishnu Priya ◽  
Vikas ◽  
Madaswamy S Muthu
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Vital Role ◽  
The Body ◽  
Innate Immune ◽  
Host Immune System ◽  
Molecular Alteration ◽  
Microbial Infections ◽  
Permanent Cure

COVID-19 is an infectious and highly contagious disease caused by SARS-CoV-2. The immunotherapy strategy has a great potential to develop a permanent cure against COVID-19. Innate immune cells are in constant motion to scan molecular alteration to cells led by microbial infections throughout the body and helps in clearing invading viruses. Harnessing immunological targets for removing viral infection, generally based on the principle of enhancing the T-cell and protective immune responses. Currently-approved COVID-19 vaccines are mRNA encapsulated in liposomes that stimulate the host immune system to produce antibodies. Given the vital role of innate immunity, harnessing these immune responses opens up new hope for the generation of long-lasting and protective immunity against COVID-19.

scholarly journals RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response

2021 ◽  
Vol 17 (3) ◽  
pp. e1009401
Author(s):  
Chenhui Li ◽  
Lele Zhang ◽  
Dong Qian ◽  
Mingxing Cheng ◽  
Haiyang Hu ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
E3 Ligase ◽  
Vital Role ◽  
Innate Immune ◽  
Type I ◽  
Pathway Activation ◽  
Sting Pathway ◽  
Signaling Activation

The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the activity of cGAS must be tightly fine-tuned to maintain immune homeostasis in antiviral response. Here, we reported that neddylation modification was indispensable for appropriate cGAS-STING signaling activation. Blocking neddylation pathway using neddylation inhibitor MLN4924 substantially impaired the induction of type I interferon and proinflammatory cytokines, which was selectively dependent on Nedd8 E2 enzyme Ube2m. We further found that deficiency of the Nedd8 E3 ligase Rnf111 greatly attenuated DNA-triggered cGAS activation while not affecting cGAMP induced activation of STING, demonstrating that Rnf111 was the Nedd8 E3 ligase of cGAS. By performing mass spectrometry, we identified Lys231 and Lys421 as essential neddylation sites in human cGAS. Mechanistically, Rnf111 interacted with and polyneddylated cGAS, which in turn promoted its dimerization and enhanced the DNA-binding ability, leading to proper cGAS-STING pathway activation. In the same line, the Ube2m or Rnf111 deficiency mice exhibited severe defects in innate immune response and were susceptible to HSV-1 infection. Collectively, our study uncovered a vital role of the Ube2m-Rnf111 neddylation axis in promoting the activity of the cGAS-STING pathway and highlighted the importance of neddylation modification in antiviral defense.

A New Approach to Study the Degradation of the Organic Pollutants by A-Doped MxOy/B Photocatalysts

2021 ◽  
Author(s):  
Mojtaba Arabameri ◽  
Hadis Bashiri
Keyword(s):  
Experimental Data ◽  
Organic Pollutants ◽  
Vital Role ◽  
Effective Concentration ◽  
Computational Method ◽  
Operational Parameters ◽  
New Approach ◽  
New Variables ◽  
Kinetics Of

Abstract This work presents a new approach and a comprehensive mechanism to study the kinetics of the photodegradation of the organic pollutants. The vital role of various operational factors on the degradation of the organic pollutants is explained using this method. The proposed approach is based on the simple strategies and a powerful computational method. Two new variables “the effective concentration of photon” (Ieff) and “the effective concentration of the reactive-centers” (RC) are defined to better understanding the effect of operational parameters on the organic pollutants photodegradation. The optimum conditions of the photocatalytic degradation can be determined with the help of this method. This approach was used to study the kinetics of photodegradation of the organic pollutants on the A - doped MxOy/B photocatalysts. The provided mechanism has been examined with the some experimental data. The high correlations between the experimental data and the fitting results under different conditions prove this mechanism could be reliable.

scholarly journals Interdependence of Museums and Tourism Industry in Jordan

2019 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Nermeen Khasawneh
Keyword(s):  
Historical Development ◽  
Current Knowledge ◽  
Descriptive Analysis ◽  
Vital Role ◽  
Tourism Industry ◽  
Current Status ◽  
Tourist Destinations ◽  
Domestic Tourism ◽  
Arabic And English

Museums are educational, cultural and recreational centers; cares for objects of scientific, artistic, cultural, or historical value and other artifacts linked to the cultural and popular heritage of particular people, exhibiting and preserving these collections for subsequent generations. Heritage is the basis of civilization as it represents the nation's memory and a bridge linking its authenticity with its present and future as well as the foundations of its representation and identity. The aims of this retrospective study are to review the consistence and historical development of the Jordanian museums and to evaluate its current status, its contribution in sustainable tourism industry and to adjoin a new contribution to the current knowledge in this field. This study based on two approaches; the first was conducted on the numbers of visitors to five selected museums in Jordan for the years 2016-2017, taking into account the residence variable. The second approach used a sort specially designed questionnaires, written in Arabic and English languages were given non- selectively to (120) visitors, designed to determine the role of museums in supporting tourism in Jordan. Data were collected and a descriptive analysis was performed. The findings of this study revealed that museums play a prominent role in supporting the tourism industry through its active educational and recreational activities (94.33%), supporting domestic tourism (92.67%), and promote loyalty and national identity (92.33%). Our study confirmed the vital role of museums in the tourism industry, which in turn provides a fundamental tributary to the Jordanian Gross Domestic Product. The diversified Jordanian museums with its authentic holdings, in addition to the unique tourist destinations call for immediate support to boost Jordanian tourism globally.

scholarly journals Arthritogenic Alphavirus-Induced Immunopathology and Targeting Host Inflammation as A Therapeutic Strategy for Alphaviral Disease

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 290 ◽  
Author(s):  
Helen Mostafavi ◽  
Eranga Abeyratne ◽  
Ali Zaid ◽  
Adam Taylor
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Current Knowledge ◽  
Symptomatic Relief ◽  
Innate Immune ◽  
Host Immune System ◽  
Inflammatory Drugs ◽  
Global Concern ◽  
Alphavirus Infection

Arthritogenic alphaviruses are a group of medically important arboviruses that cause inflammatory musculoskeletal disease in humans with debilitating symptoms, such as arthralgia, arthritis, and myalgia. The arthritogenic, or Old World, alphaviruses are capable of causing explosive outbreaks, with some viruses of major global concern. At present, there are no specific therapeutics or commercially available vaccines available to prevent alphaviral disease. Infected patients are typically treated with analgesics and non-steroidal anti-inflammatory drugs to provide often inadequate symptomatic relief. Studies to determine the mechanisms of arthritogenic alphaviral disease have highlighted the role of the host immune system in disease pathogenesis. This review discusses the current knowledge of the innate immune response to acute alphavirus infection and alphavirus-induced immunopathology. Therapeutic strategies to treat arthritogenic alphavirus disease by targeting the host immune response are also examined.

scholarly journals Role of immune response in Yersinia pestis infection

2011 ◽  
Vol 5 (09) ◽  
pp. 628-639 ◽  
Author(s):  
Amedeo Amedei ◽  
Elena Niccolai ◽  
Luigi Marino ◽  
Mario Milco D'Elios
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Far East ◽  
Adaptive Immune Response ◽  
Host Immune System ◽  
Adaptive Immune ◽  
Response Versus ◽  
North And South America ◽  
North And South

Yersinia pestis (Y. Pestis) is an infamous pathogen causing plague pandemics throughout history and is a selected agent of bioterrorism threatening public health. Y. pestis was first isolated by Alexandre Yersin in 1894 in Hong Kong and in the years to follow from all continents. Plague is enzootic in different rodents and their fleas in Africa, North and South America, and Asia such as Middle/Far East and ex-USSR countries. Comprehending the multifaceted interaction between Y. pestis and the host immune system will enable us design more effective vaccines. Innate immune response and both component (humoral and cellular) of adaptive immune response contribute to host defense against Y.pestis infection, but the bacterium possess different mechanisms to counteract the immune response. The aims of this review are to analyze the role of immune response versus Yersinia pestis infection and to highlight the various stratagems adopted by Y. pestis to escape the immunological defenses.

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