Hypoxia-driven secretion of extracellular matrix proteins in the exosomes reflects the asymptomatic pathology of rotator cuff tendinopathies

The major hallmark of rotator cuff tendinopathies (RCT) is the disorganization of the tendon extracellular matrix (ECM), which is due to a decrease in the ratio of collagen I to collagen III. In addition, the pathology of the tendon matrisome remains asymptomatic, and hypoxia has been identified to be the priming signal to initiate the molecular pathology of RCT. Also, the secretome content of hypoxia-challenged tendon cells (tenocytes) reflects the pathological status of RCT. With this background, the present study was designed to establish the expression status and molecular crosstalk of the ECM component proteins contained in the exosomes of the hypoxia-challenged swine tenocytes. The mass spectrometry analysis revealed the upregulation of COL1A2, P4HA1, PRDX2, P3H1, COL6A1, PPIB, LCN1, and COL3A1 and the downregulation of COLA12, PDIA4, COLG, FN1, CTSK, and TNC in the exosomes of hypoxic tenocytes. These proteins interact with diverse proteins and operate multiple pathways associated with ECM homeostasis and repair as determined by NetworkAnalyst. The functional analysis of these proteins reflects the pathology of tendon ECM, which is correlated with the asymptomatic phase of RCT. Understanding the signaling mediated by these proteins would reveal the underlying molecular pathology and offers translational significance in the diagnosis and management of RCT.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Regulatory role of cardiomyocyte metabolism via AMPK activation in modulating atrial structural, contractile, and electrical properties following atrial fibrillation

The number of patients diagnosed with atrial fibrillation (AF) has been rising due to increased incidence, enhanced detection methods, and greater survival rates following diagnosis. Due to this increase, AF is now the most commonly diagnosed arrhythmia in clinical practice. AF is characterized by irregular, high-frequency contractions of atrial myocytes that lead to turbulent blood flow and the potential for thrombus formation, stroke, or heart failure. These high-frequency contractions of the atrial myocytes cause an imbalance between metabolic supply and demand. Although advances have been made in understanding the pathophysiology of AF, the etiology and underlying pathogenic mechanism remain unknown. However, recent evidence suggests that cardiomyocyte metabolism involving 5′ AMP-activated protein kinase (AMPK) activation is altered in patients with AF. Here, we critically reviewed the current understanding of AMPK activation in AF and how it could affect structural, contractile, and electrophysiological cellular properties in the pathogenesis of AF.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Novel Approaches to Program Cells to Differentiate into Cardiomyocytes in Myocardial Regeneration

With heart failure (HF) being one of the leading causes of hospitalization and death worldwide, multiple stem cell therapies have been attempted to accelerate the regeneration of the infarct zone. Versatile strategies have emerged to establish the cell candidates of cardiomyocyte lineage for regenerative cardiology. This article illustrates critical insights into the emerging technologies, current approaches, and translational promises on the programming of diverse cell types for cardiac regeneration

Intelligent Hydrogels in Myocardial Regeneration and Engineering

Myocardial infarction (MI) causes impaired cardiac function due to the loss of cardiomyocytes following an ischemic attack. Intelligent hydrogels offer promising solutions for post-MI cardiac tissue therapy to aid in structural support, contractility, and targeted drug therapy. Hydrogels are porous hydrophilic matrices used for biological scaffolding, and upon the careful alteration of ideal functional groups, the hydrogels respond to the chemistry of the surrounding microenvironment, resulting in intelligent hydrogels. This review delves into the perspectives of various intelligent hydrogels and evidence from successful models of hydrogel-assisted treatment strategies

H&E staining of biceps tendons—Group-1 (Patient numbers—PT3, PT6, PT8 and PT10) and Group-2 (Patient numbers–PT2, PT4, PT13 and PT9).

<p>The green arrows show tendon cells; black arrows point inflammation; red arrows indicate angiogenesis; blue arrows show ECM disorganization; violet arrows point fatty infiltration; and yellow arrows indicate normal ECM with dense collagen deposition. The inflammation and fatty infiltration were not evident in Group-2 while ECM disorganization was less prominent compared to Group-1. The figures are shown in 400x magnification.</p

Flow cytometry analysis of TREM-1 and TREM-2 expression on CD16⁺ and CD14⁺ cells.

<p>(A) Representative images for the gating of the cells in Group-1 and Group-2 patients. (B) Comparison between Group-1 and Group-2 patients showing increased TREM-1 expression in the cells of Group-1 revealing the severity of inflammation. <i>n = 8 for both the groups</i>, <i>* p<0</i>.<i>05; NS–Not significant</i></p

Mean fluorescence intensity for the evaluation of gene expression analysis by immunofluorescence using ImageJ software.

<p>The expression levels of CD68, TREM-1, HMGB1 and RAGE were significantly higher in the tissues of Group-1 when compared to Group-2. TREM-2 expression was enhanced in Group-1 but was not significant. The expression of TM and SLX between both the groups was mostly similar and not significant. <i>Group-1 (n = 4)</i>, <i>Group-1 (n = 11) * p<0</i>.<i>05; NS–Not significant</i>.</p

Primers and their sequences used for RT-PCR analysis.

<p>Primers and their sequences used for RT-PCR analysis.</p