Tendon healing in presence of chronic low-level inflammation: a systematic review

2019 ◽  
Vol 132 (1) ◽  
pp. 97-116 ◽  
Author(s):  
Emanuele Chisari ◽  
Laura Rehak ◽  
Wasim S Khan ◽  
Nicola Maffulli
Keyword(s):  
Ex Vivo ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Activity Level ◽  
Cochrane Library ◽  
Low Level ◽  
Mesh Terms ◽  
The Subject ◽  
Inflammatory Molecules

Abstract Background Tendinopathy is a common musculoskeletal condition affecting subjects regardless of their activity level. Multiple inflammatory molecules found in ex vivo samples of human tendons are related to the initiation or progression of tendinopathy. Their role in tendon healing is the subject of this review. Sources of data An extensive review of current literature was conducted using PubMed, Embase and Cochrane Library using the term ‘tendon’, as well as some common terms of tendon conditions such as ‘tendon injury OR (tendon damage) OR tendonitis OR tendinopathy OR (chronic tendonitis) OR tendinosis OR (chronic tendinopathy) OR enthesitis’ AND ‘healing’ AND ‘(inflammation OR immune response)’ as either key words or MeSH terms. Areas of agreement An environment characterized by a low level of chronic inflammation, together with increased expression of inflammatory cytokines and growth factors, may influence the physiological tendon healing response after treatment. Areas of controversy Most studies on this topic exhibited limited scientific translational value because of their heterogeneity. The evidence associated with preclinical studies is limited. Growing points The role of inflammation in tendon healing is still unclear, though it seems to affect the overall outcome. A thorough understanding of the biochemical mediators of healing and their pathway of pain could be used to target tendinopathy and possibly guide its management. Areas timely for developing research We require further studies with improved designs to effectively evaluate the pathogenesis and progression of tendinopathy to identify cellular and molecular targets to improve outcomes.

scholarly journals Tendon healing is adversely affected by low-grade inflammation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emanuele Chisari ◽  
Laura Rehak ◽  
Wasim S. Khan ◽  
Nicola Maffulli
Keyword(s):  
Proteolytic Enzymes ◽  
Tendon Healing ◽  
Negative Influence ◽  
Tendon Injury ◽  
Low Grade ◽  
Molecular Pathways ◽  
Low Grade Inflammation ◽  
Late Stages ◽  
Primary Injury

Abstract Background Tendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation. Main findings There has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways. Conclusion This review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing.

scholarly journals The role of the immune system in tendon healing: a systematic review

2020 ◽  
Vol 133 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Emanuele Chisari ◽  
Laura Rehak ◽  
Wasim S Khan ◽  
Nicola Maffulli
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
Immune System ◽  
Mast Cells ◽  
Immune Cells ◽  
Tendon Healing ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Healing Response

Abstract Introduction The role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the ‘immune cells’ and their cytokine production. This systematic review reports how the immune system affects tendon healing. Sources of data We registered our protocol (registration number: CRD42019141838). After searching PubMed, Embase and Cochrane Library databases, we included studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. The PRISMA guidelines were applied, and risk of bias and the methodological quality of the included studies were assessed. We excluded all the articles with high risk of bias and/or low quality after the assessment. We included 62 articles assessed as medium or high quality. Areas of agreement Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors which could affect both healing and macrophage polarization. Areas of controversy The role of lymphocytes, mast cells and polymorphonucleocytes is still inconclusive. Growing points The immune system is a major actor in the complex mechanism behind the healing response occurring in tendons after an injury. A dysregulation of the immune response can ultimately lead to a failed healing response. Areas timely for developing research Further studies are needed to shed light on therapeutic targets to improve tendon healing and in managing new way to balance immune response.

scholarly journals Dentinal Microcracks after Root Canal Instrumentation Using Instruments Manufactured with Different NiTi Alloys and the SAF System: A Systematic Review

2021 ◽  
Vol 11 (11) ◽  
pp. 4984
Author(s):  
Kashmira Sawant ◽  
Ajinkya M. Pawar ◽  
Kulvinder Singh Banga ◽  
Ricardo Machado ◽  
Mohmed Isaqali Karobari ◽  
...  
Keyword(s):  
Web Of Science ◽  
Cochrane Library ◽  
Lower Prevalence ◽  
Systematic Analysis ◽  
Niti Alloys ◽  
System A ◽  
Mesh Terms ◽  
Mechanical Preparation ◽  
The Subject ◽  
Root Canal Instrumentation

Aim: The aim of this systematic analysis was to assess the prevalence of dentinal microcracks at various levels (3, 6, and 9mm from the apex) after using instruments made with conventional, R-Phase, and M-Wire NiTi alloys and the SAF system. Materials and Methods: Electronic searches were conducted in the databases Embase, Cochrane Library, Scopus, PubMed, and Web of Science. To arrange search methods, “MeSH” terms and/or keywords typically associated with the subject were paired with the Boolean operators “AND” and “OR.” Additional searches were conducted on the websites of four separate endodontic journals. After reading the titles and excluding duplicates, 1000 of the 1343 documents originally found were eliminated. Upon reviewing the abstracts, 310 of the remaining 343 experiments were also eliminated. Based on qualifying requirements, only 13 of the remaining 33 articles were included in the qualitative review. Results: All systems triggered dentinal microcracks; however, when chemo-mechanical preparation was performed using Self-Adjusting File (SAF) and systems manufactured with R-phase technology—K3XF and Twisted File Adaptive (TFA)—less of these defects were found when compared to those manufactured with traditional NiTi—ProTaper Universal and Mtwo—and with M-Wire—ProTaper Next, Reciproc, and WaveOne. Conclusions: A lower prevalence of dentinal microcracks was observed after using SAF and endodontic systems manufactured with R-phase.

scholarly journals The Roles of MicroRNAs in Tendon Healing and Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Lingli Ding ◽  
Min Wang ◽  
Shengnan Qin ◽  
Liangliang Xu
Keyword(s):  
Tendon Healing ◽  
Tendon Injury ◽  
Transcriptional Level ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Rehabilitation Programs ◽  
Tenogenic Differentiation ◽  
Wide Range ◽  
Significant Disability

Tendons connect the muscle abdomen of skeletal muscles to the bone, which transmits the force generated by the muscle abdomen contraction and pulls the bone into motion. Tendon injury is a common clinical condition occurring in certain populations, such as repeated tendon strains in athletes. And it can lead to substantial pain and loss of motor function, in severe cases, significant disability. Tendon healing and regeneration have attracted growing interests. Some treatments including growth factors, stem cell therapies and rehabilitation programs have been tried to improve tendon healing. However, the basic cellular biology and pathology of tendons are still not fully understood, and the management of tendon injury remains a considerable challenge. Regulating gene expression at post-transcriptional level, microRNA (miRNA) has been increasingly recognized as essential regulators in the biological processes of tendon healing and regeneration. A wide range of miRNAs in tendon injury have been shown to play vital roles in maintaining and regulating its physiological function, as well as regulating the tenogenic differentiation potential of stem cells. In this review, we show the summary of the latest information on the role of miRNAs in tendon healing and regeneration, and also discuss potentials for miRNA-directed diagnosis and therapy in tendon injuries and tendinopathy, which may provide new theoretical foundation for tenogenesis and tendon healing.

scholarly journals The Role of Hydroxychloroquine in COVID-19 Treatment: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 49 (10) ◽  
Author(s):  
Amir Shamshirian ◽  
Amirhossein Hessami ◽  
Keyvan Heydari ◽  
Reza Alizadeh-Navaei ◽  
Mohammad Ali Ebrahimzadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Group ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Mesh Terms ◽  
Significant Difference ◽  
Mortality Difference ◽  
Meta Regression Analysis ◽  
And Control

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease. Keywords: Azithromycin, coronavirus outbreaks, pandemic, SARS-CoV-2 disease

scholarly journals Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in ligament or tendon healing: A Systematic Review from 1998-2018

2020 ◽  
Vol 8 (5_suppl5) ◽  
pp. 2325967120S0010
Author(s):  
Sholahuddin Rhatomy ◽  
Tito Sumarwoto ◽  
Andhi Prijosedjati ◽  
Romaniyanto ◽  
Thomas Edison Prasetyo
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Conditioned Medium ◽  
Tendon Healing ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Cochrane Library

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome. Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in ligament or tendon healing from 1998 until 2018. Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus, Google scholar, and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, ligament, tendon and healing. Methods: A total of 904 articles were reviewed. Five articles were identified as relevant for this systematic literature review. Results: One tables of studies were constructed for in vitro studies and in-vivo studies. Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of ligament or tendon healing at various stages in vitro or in vivo. Although there are no clinical studies regarding the use of CM- MSC in the human ligament or tendon healing that have been conducted, transplantation of secretome has shown a promising result in the acceleration of ligament or tendon healing process.

scholarly journals Cachexia and anorexia in cancer; a systematic review

2020 ◽  
Vol 7 (2) ◽  
pp. e20-e20
Author(s):  
Ali Darakhshandeh ◽  
Mahnaz Momenzadeh
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Cancer Cachexia ◽  
Cochrane Library ◽  
Mesh Terms ◽  
The Subject ◽  
Cancer Anorexia ◽  
Cachexia Syndrome ◽  
Expected Outcomes

The treatment strategy for cancer cachexia is based on the cachexia stage of the cancer and its phenotypes, therefore interventions and expected outcomes vary. In order for the patient to get the most out of the treatment, it should be done based on the mechanism of intervention and the quality of life of patients should be addressed, including aspects of rehabilitation and reduction of the patient’s suffering using a multidisciplinary team. Given the importance of the subject, the present study aims to investigate cachexia and anorexia in cancer. From the electronic databases, PubMed, Cochrane Library, Embase, Web of Sciences have been used to perform a systematic literature until 2020. Therefore, a software program (Endnote X8) has been utilized for managing electronic titles. Searches were performed with mesh terms. This review recommended that clinicians establish an interaction between cancer anorexia-cachexia syndrome (CACS) treatments and chronic pain treatments and choose the best treatment option.

scholarly journals The Role of Hydroxychloroquine in COVID-19 Treatment: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Amir Shamshirian ◽  
Amirhossein Hessami ◽  
Keyvan Heydari ◽  
Reza Alizadeh-Navaei ◽  
Mohammad Ali Ebrahimzadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Group ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Mesh Terms ◽  
Significant Difference ◽  
Mortality Difference ◽  
Meta Regression Analysis ◽  
And Control

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google-Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ+AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease. Keywords: Azithromycin, coronavirus outbreaks, pandemic, 2019-nCoV disease

scholarly journals Adipose-derived Mesenchymal Stem Cell-derived Exosomes Promote Tendon Healing by Activating Both SMAD1/5/9 and SMAD2/3

2021 ◽  
Author(s):  
Hengchen Liu ◽  
Mingzhao Zhang ◽  
Manyu Shi ◽  
Tingting Zhang ◽  
Wenjun Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Subcutaneous Fat ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Sprague Dawley ◽  
Tenogenic Differentiation

Abstract Background: The use of adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) may become a new therapeutic method in biomedicine owing to their important role in regenerative medicine. However, the role of ADSC-Exos in tendon repair has not yet been evaluated. Therefore, we aimed to clarify the healing effects of ADSC-Exos on tendon injury.Methods: The adipose-derived mesenchymal stem cells (ADSCs) and tendon stem cells (TSCs) were isolated from subcutaneous fat and tendon tissues of Sprague Dawley rats, respectively, and exosomes were isolated from ADSCs. The proliferation and migration of TSCs induced by ADSC-Exos were analyzed by EdU, cell scratch and transwell assays. We used western blot to analyze tenogenic differentiation of TSCs and the role of the SMAD signaling pathways. Then we explored a new treatment method for tendon injury, combining exosome therapy with local targeting using a biohydrogel. Immunofluorescence and immunohistochemistry were used to detect the expression of inflammatory and tenogenic differentiation after tendon injury, respectively. The quality of tendon healing was evaluated by Hematoxylin-eosin (H&E) staining and biomechanical testing.Results: ADSC-Exos could be absorbed by TSCs, and promoted the proliferation, migration, and tenogenic differentiation of these cells. This effect may have depended on activation of the SMAD2/3 and SMAD1/5/9 pathways. Furthermore, ADSC-Exos inhibited the early inflammatory reaction and promoted tendon healing in vivo.Conclusions: Overall, we demonstrated that ADSC-Exos contributed to tendon regeneration and provided proof of concept of a new approach for treating tendon injuries.

scholarly journals Do Mast Cells Have a Role in Tendon Healing and Inflammation?

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1134
Author(s):  
Md Abdul Alim ◽  
Magnus Peterson ◽  
Gunnar Pejler
Keyword(s):  
Mast Cells ◽  
Neurogenic Inflammation ◽  
Tissue Injury ◽  
Healing Process ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Glutamate Signaling ◽  
Human Tendon ◽  
Injured Tendon

Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis/pain after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. The mechanisms driving such neurogenic inflammation are presently not clear. However, it has recently been demonstrated that mast cells present within the injured tendon can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling and thereby modulate neurogenic inflammation following tissue injury. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury.

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