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Probe-based confocal endomicroscopy provides real time videos of autoflourescent elastin structures within the alveoli. With it, multiple changes in the elastin structure due to different diffuse parenchymal lung diseases have previously been described. However, these evaluations have mainly relied on qualitative evaluation by the examiner and manually selected parts post-examination. To develop a fully automatic method for quantifying structural properties of the imaged alveoli elastin and to perform a preliminary assessment of their diagnostic potential. 46 patients underwent probe-based confocal endomicroscopy, of which 38 were divided into 4 groups categorizing different diffuse parenchymal lung diseases. 8 patients were imaged in representative healthy lung areas and used as control group. Alveolar elastin structures were automatically segmented with a trained machine learning algorithm and subsequently evaluated with two methods developed for quantifying the local thickness and structural connectivity. The automatic segmentation algorithm performed generally well and all 4 patient groups showed statistically significant differences with median elastin thickness, standard deviation of thickness and connectivity compared to the control group. Alveoli elastin structures can be quantified based on their structural connectivity and thickness statistics with a fully-automated algorithm and initial results highlight its potential for distinguishing parenchymal lung diseases from normal alveoli.

The function of connective tissues depends on the physical and biochemical properties of their extracellular matrix (ECM), which are in turn dictated by ECM protein composition. With the primary objective of obtaining quantitative estimates for absolute and relative amounts of ECM proteins, we performed a systematic review of papers reporting protein composition of human connective tissues. Articles were included in meta-analysis if they contained absolute or relative quantification of proteins found in the ECM of human bone, adipose tissue, tendon, ligament, cartilage and skeletal muscle. We generated absolute quantitative estimates for collagen in articular cartilage, intervertebral disk (IVD), skeletal muscle, tendon, and adipose tissue. In addition, sulfated glycosaminoglycans were quantified in articular cartilage, tendon and skeletal muscle; total proteoglycans in IVD and articular cartilage, fibronectin in tendon, ligament and articular cartilage, and elastin in tendon and IVD cartilage. We identified significant increases in collagen content in the annulus fibrosus of degenerating IVD and osteoarthritic articular cartilage, and in elastin content in degenerating disc. In contrast, collagen content was decreased in the scoliotic IVD. Finally, we built quantitative whole-tissue component breakdowns. Quantitative estimates improve our understanding of composition of human connective tissues, providing insights into their function in physiology and pathology.

Background: For periorbital rejuvenation, injection of botulinum toxin A (BoNT/A) is known to improve both static as well as dynamic wrinkles. A microneedle fractional radiofrequency (MFR) device was recently developed and is a novel and promising tool. Objective: This study compares the effects of these two treatment modalities on periorbital static wrinkles and lines. Methods: Twelve healthy women aged 20-59 years with periorbital wrinkles participated in this study. Each patient received one session of intradermal injection of BoNT/A on the left periorbital area and three sessions of MFR on the right. Clinical improvement, skin elasticity and subjective satisfaction were evaluated at every visit (baseline, 3, 6 and 18 weeks). Results: BoNT/A injection showed superior effects at 3 and 6 weeks. However, the MFR device showed better improvement at 18 weeks. In skin biopsies, the expression of procollagen 3 and elastin was increased on the MFR side compared to the untreated skin and the BoNT/A injection side. The patient satisfaction surveys at 3 weeks showed better satisfaction on the BoNT/A treatment side compared to the MFR treatment side. At 18 weeks, there were no significant differences in patient satisfaction between the two sides. Conclusion: BoNT/A injection rapidly improved periorbital wrinkles, but the effect decreased up to week 18. Compared to BoNT/A injection, MFR therapy showed gradual and long-term improvement in periorbital rejuvenation.

Objectives: This study examines the elastic fiber and hyaluronic acid (HA) content of the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: Lamina propria elastin was quantified by measuring the amino acid desmosine, and HA was measured by an enzyme-linked immunosorbent assay-based technique. Quantitative histology was used to evaluate elastin and HA levels in specific LP regions. The distributions of fibrillin-1, a primary microfibrillar component of elastic fibers, and of tropoelastin, an indicator of elastin synthesis, were immunohistochemically analyzed. Results: Elastin and HA constituted 8.5% ± 2.1% and 0.82% ± 0.11% of human LP, respectively, relative to tissue total protein. Although the mean LP desmosine levels were similar across species, the mean HA levels in canine (p < 3.1 × 10−5), porcine (p < 1.5 × 10−5), and ferret (p < 6.6 × 10−4) LPs were 3 to 4 times higher than that in humans. Marked interspecies differences in elastin, fibrillin-1, tropoelastin, and HA distributions were observed histologically. Conclusions: The elastin content of the human LP is roughly twice that of the dermis, whereas the HA content of the human LP is similar to that of the dermis. Although all species had similar levels of desmosine, histologic evaluation indicates that the porcine elastin distribution is most similar to that of the human LP. Fibrillin-1 staining suggests that stress in the human LP may be particularly high in the superior superficial layer, and tropoelastin staining indicates that the rate of LP elastin turnover may vary spatially.

We report a multiplexed imaging mass spectrometry method which spatially localizes and selectively accesses the extracellular matrix on formalin-fixed paraffin-embedded tissue sections. The extracellular matrix (ECM) consists of (1) fibrous proteins, post-translationally modified (PTM) via N- and O-linked glycosylation, as well as hydroxylation on prolines and lysines, and (2) glycosaminoglycan-decorated proteoglycans. Accessing all these components poses a unique analytical challenge. Conventional peptide analysis via trypsin inefficiently captures ECM peptides due to their low abundance, intra- and intermolecular cross-linking, and PTMs. In previous studies, we have developed matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) techniques to capture collagen peptides via collagenase type III digestion, both alone and after N-glycan removal via PNGaseF digest. However, in fibrotic tissues, the buildup of ECM components other than collagen-type proteins, including elastin and glycosaminoglycans, limits efficacy of any single enzyme to access the complex ECM. Here, we have developed a novel serial enzyme strategy to define the extracellular matrix, including PTMs, from a single tissue section for MALDI-IMS applications.

Fibrotic diseases are characterized by progressive and often irreversible scarring of connective tissue in various organs, leading to substantial changes in tissue mechanics largely as a result of alterations in collagen structure. This is particularly important in the lung because its bulk modulus is so critical to the volume changes that take place during breathing. Nevertheless, it remains unclear how fibrotic abnormalities in the mechanical properties of pulmonary connective tissue can be linked to the stiffening of its individual collagen fibers. To address this question, we developed a network model of randomly oriented collagen and elastin fibers to represent pulmonary alveolar wall tissue. We show that the stress–strain behavior of this model arises via the interactions of collagen and elastin fiber networks and is critically dependent on the relative fiber stiffnesses of the individual collagen and elastin fibers themselves. We also show that the progression from linear to nonlinear stress–strain behavior of the model is associated with the percolation of stress across the collagen fiber network, but that the location of the percolation threshold is influenced by the waviness of collagen fibers.

Background Skin's exposure to intrinsic and extrinsic factors causes age‐related changes, leading to a lower amount of dermal collagen and elastin. Aim This study investigated the effects of a novel facial muscle stimulation technology combined with radiofrequency (RF) heating on dermal collagen and elastin content for the treatment of facial wrinkles and skin laxity. Methods The active group subjects (N = 6) received four 20‐min facial treatments with simultaneous RF and facial muscle stimulation, once weekly. The control subject (N = 1) was untreated. Skin biopsies obtained at baseline, 1‐month and 3‐month follow‐up were evaluated histologically to determine collagen and elastin fibers content. A group of independent aestheticians evaluated facial skin appearance and wrinkle severity. Patient safety was followed. Results In the active group, collagen‐occupied area reached 11.91 ± 1.80 × 106 μm2 (+25.32%, p < 0.05) and 12.35 ± 1.44 × 105 μm2 (+30.00%, p < 0.05) at 1‐month and 3‐month follow‐up visits. Elastin‐occupied area at 1‐month and 3‐month follow‐up was 1.64 ± 0.14 × 105 μm2 (+67.23%, p < 0.05), and 1.99 ± 0.21 × 105 μm2 (+102.80%, p < 0.05). In the control group, there was no significant difference (p > 0.05) in collagen and elastin fibers. Active group wrinkle scores decreased from 5 (moderate, class II) to 3 (mild, class I). All subjects, except the control, improved in appearance posttreatment. No adverse events or side effects occurred. Conclusion Decreased dermal collagen and elastin levels contributes to a gradual decline in skin elasticity, leading to facial wrinkles and unfirm skin. Study results showed noticeable improvement in facial appearance and increased dermal collagen and elastin content subsequent to simultaneous, noninvasive RF, and facial muscle stimulation treatments.

PurposeLumbar spinal canal stenosis (LSCS) is associated with fibrosis, decreased elastin-to-collagen ratio, and hypertrophy of the ligamentum flavum (LF). Diabetes mellitus (DM) is known to cause metabolic disturbances within the extracellular matrix in multiple tissues. These alterations may play a major role in the severity of clinical symptoms of LSCS affecting diabetic patients. We aimed to examine the hypothesis that DM may contribute to the LF changes seen in patients with LSCS.MethodsThe study cohort included 29 patients: 23 with LSCS (10 with DM vs. 13 without DM) as well as six patients with lumbar disc herniation (LDH). Surgical LF specimens were retrieved for histological assessment. Morphologic quantification of confocal microscopy images using fast Fourier transform analysis allowed us to compare anisotropy and elastin fiber orientation between groups.ResultsThere was a significant positive correlation between fasting plasma glucose values and degree of elastin degradation (r = 0.36, p = 0.043). The diabetic patients with LSCS showed a significantly greater loss of elastic fibers (2.3 ± 0.9 vs. 1.5 ± 0.55, p = 0.009), although fibrosis was shown to be similar (1.44 ± 0.7 vs. 1.43 ± 0.88, p = 0.98). There was no significant difference in the degree of calcification in the LSCS group between patients with and without diabetes (1.71 vs. 2.05%, p = 0.653). Fiber orientation was found to be less homogenous in the LSCS compared with the LDH group, although not significantly affected by DM.ConclusionsThe present study points to a significant contribution of DM to the loss of elastin fibers that occurs in the LF of patients with LSCS.

AimsVenous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited.MethodsElastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204).ResultsThe average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III–IV disease (p=0.011), but did not significantly differ among patients with stage I–II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients.ConclusionsEmploying two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.

Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.