scholarly journals Targeting Toll-Like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1291
Author(s):  
Sandra Santos-Sierra
Keyword(s):  
Inflammatory Arthritis ◽  
Therapeutic Strategy ◽  
Cellular Functions ◽  
Pharmacological Agents ◽  
Disease Modifying Drugs ◽  
Immune Attack ◽  
Current Therapies ◽  
Pros And Cons ◽  
Better Than

Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use.

Pros and Cons of Digital Textbooks Technology

2015 ◽  
pp. 227-247
Keyword(s):  
Learning Environment ◽  
Group Development ◽  
Learning Tool ◽  
Multimodal Texts ◽  
Digital Textbook ◽  
Digital Textbooks ◽  
Powerful Learning ◽  
Pros And Cons ◽  
Better Than

Students do not necessarily enjoy using textbooks. One of the main reasons is that multimodal texts are harder to process by brain patterns. Digital textbooks technology aims to reduce this pitfall, offering multimedia feedback and interactivity as the main features of the powerful learning environment. There are two ways: a) using and developing the digital textbook as a pedagogical resource and b) using and developing digital textbook as a learning tool. The first way offers speed of finding, purchasing, downloading, as well as digital reading. The second way adds the power of assembling digital content through representation in a person's own manner as well as group development of content. Educational outcomes in a digital textbook learning environment are better than in scholastic models. This chapter presents pros and cons of the digital textbook technology in concept of postmodernism philosophy. The role of the digital textbook technology for learning is proved.

scholarly journals Oncogenic role of MiR-130a in oral squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karthik Mallela ◽  
Swamy Shivananda ◽  
Kodaganur S. Gopinath ◽  
Arun Kumar
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Strategy ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Cellular Functions

AbstractAberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3′UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3′UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.

scholarly journals Oncogenic Role of miR-130a in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Karthik Mallela ◽  
Shivananda Swamy ◽  
K. Gopinath ◽  
Arun Kumar
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Strategy ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Cellular Functions

Abstract Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3’UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3’UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.

scholarly journals Role of Hormonal Manipulation in Prostate Cancer Management

1970 ◽  
Vol 2 (1) ◽  
Author(s):  
SHAH SIA
Keyword(s):  
Prostate Cancer ◽  
Turning Point ◽  
Pharmacological Agents ◽  
Cancer Management ◽  
Hormonal Manipulation ◽  
Surgical Methods ◽  
Pros And Cons ◽  
Prostate Cancer Management ◽  
Multiple Stages

Prostate cancer (PCa) treatment has seen several important developments over the last few decades in the form of improved surgical methods and advanced radiotherapy techniques but androgen deprivation therapy (ADT) still remains the cornerstone of medical management of this common male malignancy. The discovery of androgen-dependent nature of PCa about three-quarters of a century ago was a turning point that has since led to the development of various pharmacological agents which rely on the basic principle of hormonal manipulation in the form of ADT to alter disease progression. Initially employed for metastatic disease only, ADT for PCa in the current clinical practice finds use multiple stages of the disease. The present review summarises the chronological evolution of agents used for hormonal manipulation in the management of PCa, highlighting the pros and cons of each and sheds light on the potential future advances in this area.

Examining the Role of Language in Play Among Children With and Without Developmental Disabilities

2020 ◽  
Vol 51 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Elizabeth J. Short ◽  
Rachael Cooper Schindler ◽  
Rita Obeid ◽  
Maia M. Noeder ◽  
Laura E. Hlavaty ◽  
...  
Keyword(s):  
Developmental Disabilities ◽  
Autism Spectrum ◽  
Free Play ◽  
Group Differences ◽  
Typically Developing ◽  
Play Skills ◽  
Critical Aspect ◽  
Hyperactivity Disorder ◽  
Better Than

Purpose Play is a critical aspect of children's development, and researchers have long argued that symbolic deficits in play may be diagnostic of developmental disabilities. This study examined whether deficits in play emerge as a function of developmental disabilities and whether our perceptions of play are colored by differences in language and behavioral presentations. Method Ninety-three children participated in this study (typically developing [TD]; n = 23, developmental language disorders [DLD]; n = 24, attention-deficit/hyperactivity disorder [ADHD]; n = 26, and autism spectrum disorder [ASD]; n = 20). Children were videotaped engaging in free-play. Children's symbolic play (imagination, organization, elaboration, and comfort) was scored under conditions of both audible language and no audible language to assess diagnostic group differences in play and whether audible language impacted raters' perception of play. Results Significant differences in play were evident across diagnostic groups. The presence of language did not alter play ratings for the TD group, but differences were found among the other diagnostic groups. When language was audible, children with DLD and ASD (but not ADHD) were scored poorly on play compared to their TD peers. When language was not audible, children with DLD were perceived to play better than when language was audible. Conversely, children with ADHD showed organizational deficits when language was not available to support their play. Finally, children with ASD demonstrated poor play performance regardless of whether language was audible or not. Conclusions Language affects our understanding of play skills in some young children. Parents, researchers, and clinicians must be careful not to underestimate or overestimate play based on language presentation. Differential skills in language have the potential to unduly influence our perceptions of play for children with developmental disabilities.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

Determinants of English as language choice among Unaccompanied Migrant Children (UMC) in Makassar, Indonesia

2019 ◽  
Vol 2 (2) ◽  
pp. 1-7
Author(s):  
Andi Samsu Rijal ◽  
Andi Mega Januarti Putri
Keyword(s):  
Language Choice ◽  
Migrant Children ◽  
Immigrant Communities ◽  
The Public ◽  
International Language ◽  
Language User ◽  
Public Area ◽  
Better Than ◽  
Language Mastery

The essence of language is human activity. Communication with language is carried out through two basic human activities; speaking and listening during the interaction in a group of people. Immigrants in Makassar city communicate with immigrant communities and Makassar people. They used English and Indonesia to communicate with others. The aims of this article were to find out determinant factors of English as language choice among Unaccompanied Migrant Children (UMC) in Makassar and why they used English as their language choice to communicate with other people out of them. The data were taken from UMC in the shelter under the auspices of Makassar’s Social Office and in the public area of Makassar. This research was a qualitative approach; it was from a sociolinguistic perspective and focuses its analysis with the language choice among UMC. This research showed that most immigrants chose English as their language choice since they were in Makassar because they have acquired better than other international language and it has been mastered naturally by doing social interaction among themselves and people outside their community. UMC had more difficulties to socialize with Indonesian than the adult of Immigrants. Other than their lack of language mastery, they also have the anxiety to adapt to other immigrants and Makassar people. English was used by UMC to show their status as a foreigner who lived in a multicultural situation. Language becomes a power for a human being and it becomes a social identity for language user in one community. During the interaction of UMC in Makassar city, the role of English as an International language is shown.

ANALYSIS OF APPLICATION OF BLOCKCHAIN TECHNOLOGIES FOR THE BANKING SECTOR

2017 ◽  
Author(s):  
Svitlana Ilkovych ◽  
◽  
Maryna Korol ◽  
Keyword(s):  
Banking Sector ◽  
Blockchain Technology ◽  
Current State ◽  
Global Banking ◽  
Banking Institutions ◽  
Pros And Cons ◽  
Further Development

The article considers the essence of blockchain technology and the possibility of its application in the banking sector. The current state of development and application of blockchain technologies in various industries is analyzed. The pros and cons of using blockchain technologies for the banking sector are identified. Emphasis is placed on the role of blockchain technologies in the further development of the banking sector. The most promising directions of development of this technology are considered. Particular attention is paid to examples of the use of blockchain technology by global banking institutions.

The Role of Chess in the Intellectual Development of Childrens from Primary School

2019 ◽  
pp. 58-62
Author(s):  
Vlad Stegariu ◽  
Simona Andreea Popușoi ◽  
Beatrice Abălașei ◽  
Nicolae Lucian Voinea ◽  
Ioan Stelescu ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Primary School ◽  
Intellectual Development ◽  
Resources Allocation ◽  
Control Group ◽  
Cognitive Resources ◽  
One Year ◽  
Better Than ◽  
Chess Playing

Chess playing has a significant role in participants’ resources allocation, both at a psychological level, but mostly concerning the cognitive resources. The aim of the present study was to examine the effect of chess playing on the intellectual development of primary-class students. 67 children were tested using the Raven Standard Progressive Matrices and were distributed in three different groups according to their experience with chess, namely: the control group (formed by students with no experience with chess playing), the beginners group (students with less than one year in chess playing training) and the advanced group (children with more than two years experience with chess). Results indicated that chess playing had a significant effect on the SPM performance, indicating that those in the advanced group performed significantly better than those in the control or in the beginners group. Conclusions of this study tap into the benefits of playing chess with a focus on the children’s’ cognitive development.

Role of Methylglyoxal in Diabetic Cardiovascular and Kidney Diseases: Insights from Basic Science for Application into Clinical Practice

2018 ◽  
Vol 24 (26) ◽  
pp. 3072-3083 ◽  
Author(s):  
Sowndramalingam Sankaralingam ◽  
Angham Ibrahim ◽  
MD Mizanur Rahman ◽  
Ali H. Eid ◽  
Shankar Munusamy
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Vascular Dysfunction ◽  
Dicarbonyl Compound ◽  
Renal Complications ◽  
Lysine Residues ◽  
Patients With Diabetes ◽  
Prevalence Of Diabetes Mellitus

Background: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound – is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as surrogate markers of MG generation in vivo. Under normal conditions, MG is detoxified by the enzyme glyoxalase 1 (Glo1), using reduced glutathione as a co-factor. Elevated levels of MG is known to cause endothelial and vascular dysfunction, oxidative stress and atherosclerosis; all of which are risk factors for cardiovascular diseases. Moreover, MG has also been shown to cause pathologic structural alterations and impair kidney function. Conversely, MG scavengers (such as N-acetylcysteine, aminoguanidine or metformin) or Nrf2/Glo1 activators (such as trans-resveratrol / hesperetin) are shown to be useful in preventing MG-induced cardiovascular and renal complications in diabetes. However, clinical evidence supporting the MG lowering properties of these agents are limited and hence, need further investigation. Conclusion: Reducing MG levels directly using scavengers or indirectly via activation of Nrf2/Glo1 may serve as a novel and potent therapeutic strategy to counter the deleterious effects of MG in diabetic complications.

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