scholarly journals Artificial Aggrecan prodrugs in the treatment of Arthrosis

2021 ◽  
Author(s):  
Pardis Tabaee Damavandi

Arthrosis (OA) is a debilitating disease which increasingly affects the geriatric population. Recent studies have shown that proteoglycan forming cartilage in human tissue is citrullinated in osteoarthritic patients and this could be the cause for the enhanced fragility in the knee joints, leading to fractures and falls. The flexibility of citrulline could be reduced compared to that of arginine as citrulline presents incorporations of rigid nitric elements as well as “condensed” proline atoms, making it resemble a metabolic byproduct of collagen and arginine. In truth, citrulline derives from the activity of multiple enzymes, both aggrecanase and arginase-1. The commentary describes causal involvement of citrullination in OA and also indicates potential therapeutic approaches to how displacing the pathological citrullinated arginine, could help patients with OA.

Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 59 ◽  
Author(s):  
Magali Humbert ◽  
María Morán ◽  
Patricia de la Cruz-Ojeda ◽  
Jordi Muntané ◽  
Tabea Wiedmer ◽  
...  

Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples.


Author(s):  
Shraddha Kochar ◽  
Mitushi Deshmukh ◽  
Neha Chitale

Patient main concerns were restriction of movements of right knee and pus discharge from wound over right knee. In this case, the main clinical findings were a substantial loss in range of motion at right knee joints. There was also fixed flexion deformity seen over right knee. Diagnosis of the case was non united operated infected case of supracondylar femur fracture right side with implant in situ. In these types of circumstances, therapeutic approaches have been demonstrated to be useful. A 35-year-old male visited the orthopaedics who referred department of physiotherapy with complaints of restriction of movement of right knee and pus discharge from wound over right knee. Patient was examine in standing and supine position .On inspection, patient keeps right hip in flexion, knee in flexion patella pointing upwards and foot in equinus. According to the research, starting weight-bearing too soon can lead to failure of implant and mal-union. Supracondylar femoral fracture is a challenging condition to deal with and is associated with many secondary complications. An important role is played by physiotherapist in rehabilitation and supracondylar femur fracture management.


2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Carolina Cunha ◽  
Cátia Gomes ◽  
Ana Rita Vaz ◽  
Dora Brites

Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κB pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.


2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.


2009 ◽  
Vol 18 (1) ◽  
pp. 34-40
Author(s):  
Karen J. Dikeman ◽  
Marta S. Kazandjian ◽  
Elbert Tun ◽  
Panina Niyazova ◽  
Tien-Tsai Tsai ◽  
...  

Abstract Patients who are dependent upon tracheostomy and/or ventilator use present a particular challenge to health-care providers. The interaction of pulmonary physiology and deglutition is complex, as illustrated in the course of patients who are in the weaning process. Speech language pathologists (SLPs) should work closely with their physician colleagues to understand the influence of multiple medical co-morbidities on intervention. In traditional medicine, the clinician's objective is to connect a patient's many symptoms and complaints to a single disease entity. However, in caring for the ventilator dependent geriatric population, a symptom such as dysphagia typically results from the interplay of various, multi-organ symptoms, and conditions. This article strives to demonstrate the “juggling act” that the physician and SLP must balance between the patient's current medical condition, pulmonary dysfunction, and disordered swallowing. Clinical case studies illustrate the benefit of swallowing intervention on quality of life. While the care of patients with tracheostomy and ventilator dependence requires a team approach, with respiratory therapy and nursing vital members, this article emphasizes the roles of the SLP and physician.


2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.


2010 ◽  
Vol 20 (2) ◽  
pp. 29-36
Author(s):  
Erin M. Wilson ◽  
Ignatius S. B. Nip

Abstract Although certain speech development milestones are readily observable, the developmental course of speech motor control is largely unknown. However, recent advances in facial motion tracking systems have been used to investigate articulator movements in children and the findings from these studies are being used to further our understanding of the physiologic basis of typical and disordered speech development. Physiologic work has revealed that the emergence of speech is highly dependent on the lack of flexibility in the early oromotor system. It also has been determined that the progression of speech motor development is non-linear, a finding that has motivated researchers to investigate how variables such as oromotor control, cognition, and linguistic factors affect speech development in the form of catalysts and constraints. Physiologic data are also being used to determine if non-speech oromotor behaviors play a role in the development of speech. This improved understanding of the physiology underlying speech, as well as the factors influencing its progression, helps inform our understanding of speech motor control in children with disordered speech and provide a framework for theory-driven therapeutic approaches to treatment.


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