scholarly journals Novel Insights Into the Multifaceted Functions of RNA n6-Methyladenosine Modification in Degenerative Musculoskeletal Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Hengzhen Li ◽  
WenFeng Xiao ◽  
Yuqiong He ◽  
Zeqin Wen ◽  
Siyuan Cheng ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Molecular Mechanisms ◽  
Musculoskeletal Diseases ◽  
Clinical Implications ◽  
Dynamic Regulation ◽  
Dynamic Modification ◽  
Key Issues ◽  
Regulatory Functions ◽  
The Relationship ◽  
Subsequent Identification

N6-methyladenosine (m6A) is an important modification of eukaryotic mRNA. Since the first discovery of the corresponding demethylase and the subsequent identification of m6A as a dynamic modification, the function and mechanism of m6A in mammalian gene regulation have been extensively investigated. “Writer”, “eraser” and “reader” proteins are key proteins involved in the dynamic regulation of m6A modifications, through the anchoring, removal, and interpretation of m6A modifications, respectively. Remarkably, such dynamic modifications can regulate the progression of many diseases by affecting RNA splicing, translation, export and degradation. Emerging evidence has identified the relationship between m6A modifications and degenerative musculoskeletal diseases, such as osteoarthritis, osteoporosis, sarcopenia and degenerative spinal disorders. Here, we have comprehensively summarized the evidence of the pathogenesis of m6A modifications in degenerative musculoskeletal diseases. Moreover, the potential molecular mechanisms, regulatory functions and clinical implications of m6A modifications are thoroughly discussed. Our review may provide potential prospects for addressing key issues in further studies.

‘The Oral Versus The Written’

Moreana ◽  
2008 ◽  
Vol 45 (Number 175) (3) ◽  
pp. 14-50 ◽  
Author(s):  
Brian Cummings
Keyword(s):  
Religious Practice ◽  
Philosophical Argument ◽  
Key Issues ◽  
Confessional Identity ◽  
The Relationship

The relationship between scripture and tradition has always been recognised as central to the controversy between More and Tyndale in the late 1520s and early 1530s. It was already one of the key issues in the English campaign against Luther instigated in 1521, and in the 1540s became one of the lynchpins of confessional identity both among Catholic theologians at Trent and in the English reformed articles of 1553. This is often seen as a doctrinal issue, but beneath the surface it can also be seen as part of a profound philosophical argument about the authority of oral and written evidence, an argument which goes back to the origins of Jewish and Christian religious practice and which continues to haunt the ecumenical concerns of today.

The 9p21 Locus and its Potential Role in Atherosclerosis Susceptibility; Molecular Mechanisms and Clinical Implications

2016 ◽  
Vol 22 (37) ◽  
pp. 5730-5737 ◽  
Author(s):  
Amir Tajbakhsh ◽  
Mohammad Khorrami ◽  
Seyed Hassanian ◽  
Malihe Aghasizade ◽  
Alireza Pasdar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Potential Role ◽  
Clinical Implications ◽  
9P21 Locus

Interoception, categorization, and symptom perception

2018 ◽  
Author(s):  
Omer Van den Bergh ◽  
Nadia Zacharioudakis ◽  
Sibylle Petersen
Keyword(s):  
Decision Making ◽  
Medical Practice ◽  
Disease Model ◽  
Clinical Implications ◽  
Symptom Perception ◽  
Symptom Reports ◽  
The Relationship ◽  
Accurate Reflection

Medical practice and the disease model importantly rely on the accuracy assumption of symptom perception: patients’ symptom reports are a direct and accurate reflection of physiological dysfunction. This implies that symptoms can be used as a read-out of dysfunction and that remedying the dysfunction removes the symptoms. While this assumption is viable in many instances of disease, the relationship between symptoms and physiological dysfunction is highly variable and, in a substantial number of cases, completely absent. This chapter considers symptom perception as a form of unconscious inferential somatic decision-making that compellingly produces consciously experienced symptoms. At a mechanistic level, this perspective removes the categorical distinction between symptoms that are closely associated with physiological dysfunction and those that are not. In addition, it brings symptom perception in accordance with general theories of perception. Some clinical implications to understand and treat symptoms poorly related to physiological dysfunction are discussed.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Knockdown of Circ_SLC39A8 protects against the progression of osteoarthritis by regulating miR-591/IRAK3 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jizhe Yu ◽  
Yushuang Qin ◽  
Naxin Zhou
Keyword(s):  
Cell Viability ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Oa Chondrocytes ◽  
Polymerase Chain ◽  
Apoptosis And Inflammation ◽  
The Relationship

Abstract Background The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA. Methods The expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter. Results Circ_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression. Conclusion Our findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.

scholarly journals Small Non-Coding-RNA in Gynecological Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1085
Author(s):  
Shailendra Kumar Dhar Dwivedi ◽  
Geeta Rao ◽  
Anindya Dey ◽  
Priyabrata Mukherjee ◽  
Jonathan D. Wren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
P Element ◽  
Gynecologic Malignancies ◽  
Diagnosis And Prognosis ◽  
Gynecological Malignancies ◽  
Non Coding Rna ◽  
Therapeutic Research ◽  
Regulatory Functions

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.

scholarly journals More than a method: trusting relationships, productive tensions, and two-way learning as mechanisms of authentic co-production

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sarah E. Knowles ◽  
Dawn Allen ◽  
Ailsa Donnelly ◽  
Jackie Flynn ◽  
Kay Gallacher ◽  
...  
Keyword(s):  
Patient Involvement ◽  
Ways Of Knowing ◽  
Knowledge Mobilisation ◽  
Academic Knowledge ◽  
Willingness To Change ◽  
Different Types ◽  
Hybrid Knowledge ◽  
Key Issues ◽  
Field Notes ◽  
The Relationship

Abstract Background Knowledge mobilisation requires the effective elicitation and blending of different types of knowledge or ways of knowing, to produce hybrid knowledge outputs that are valuable to both knowledge producers (researchers) and knowledge users (health care stakeholders). Patients and service users are a neglected user group, and there is a need for transparent reporting and critical review of methods used to co-produce knowledge with patients. This study aimed to explore the potential of participatory codesign methods as a mechanism of supporting knowledge sharing, and to evaluate this from the perspective of both researchers and patients. Methods A knowledge mobilisation research project using participatory codesign workshops to explore patient involvement in using health data to improve services. To evaluate involvement in the project, multiple qualitative data sources were collected throughout, including a survey informed by the Generic Learning Outcomes framework, an evaluation focus group, and field notes. Analysis was a collective dialogic reflection on project processes and impacts, including comparing and contrasting the key issues from the researcher and contributor perspectives. Results Authentic involvement was seen as the result of “space to talk” and “space to change”. "Space to talk" refers to creating space for shared dialogue, including space for tension and disagreement, and recognising contributor and researcher expertise as equally valuable to the discussion. ‘Space to change’ refers to space to adapt in response to contributor feedback. These were partly facilitated by the use of codesign methods which emphasise visual and iterative working, but contributors emphasised that relational openness was more crucial, and that this needed to apply to the study overall (specifically, how contributors were reimbursed as a demonstration of how their input was valued) to build trust, not just to processes within the workshops. Conclusions Specific methods used within involvement are only one component of effective involvement practice. The relationship between researcher and contributors, and particularly researcher willingness to change their approach in response to feedback, were considered most important by contributors. Productive tension was emphasised as a key mechanism in leading to genuinely hybrid outputs that combined contributor insight and experience with academic knowledge and understanding.

scholarly journals Circadian Blood Pressure Rhythm in Cardiovascular and Renal Health and Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 868
Author(s):  
Jiayang Zhang ◽  
Ruoyu Sun ◽  
Tingting Jiang ◽  
Guangrui Yang ◽  
Lihong Chen
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Molecular Mechanisms ◽  
Current Understanding ◽  
Renal Outcomes ◽  
Circadian Blood Pressure ◽  
Health And Disease ◽  
The Relationship

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.

scholarly journals Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3571
Author(s):  
Bonglee Kim ◽  
Ji-Eon Park ◽  
Eunji Im ◽  
Yongmin Cho ◽  
Jinjoo Lee ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Clinical Implications ◽  
Research Perspectives ◽  
Current Review ◽  
Gold Silver ◽  
Significant Efficacy ◽  
Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

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