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2021 ◽  
Vol 12 ◽  
Author(s):  
Sandrine Gremlich ◽  
Tiziana P. Cremona ◽  
Eveline Yao ◽  
Farah Chabenet ◽  
Kleanthis Fytianos ◽  
...  

Lung aging is characterized by lung function impairment, ECM remodeling and airspace enlargement. Tenascin-C (TNC) is a large extracellular matrix (ECM) protein with paracrine and autocrine regulatory functions on cell migration, proliferation and differentiation. This matricellular protein is highly expressed during organogenesis and morphogenetic events like injury repair, inflammation or cancer. We previously showed that TNC deficiency affected lung development and pulmonary function, but little is known about its role during pulmonary aging. In order to answer this question, we characterized lung structure and physiology in 18 months old TNC-deficient and wild-type (WT) mice. Mice were mechanically ventilated with a basal and high tidal volume (HTV) ventilation protocol for functional analyses. Additional animals were used for histological, stereological and molecular biological analyses. We observed that old TNC-deficient mice exhibited larger lung volume, parenchymal volume, total airspace volume and septal surface area than WT, but similar mean linear intercept. This was accompanied by an increase in proliferation, but not apoptosis or autophagy markers expression throughout the lung parenchyma. Senescent cells were observed in epithelial cells of the conducting airways and in alveolar macrophages, but equally in both genotypes. Total collagen content was doubled in TNC KO lungs. However, basal and HTV ventilation revealed similar respiratory physiological parameters in both genotypes. Smooth muscle actin (α-SMA) analysis showed a faint increase in α-SMA positive cells in TNC-deficient lungs, but a marked increase in non-proliferative α-SMA + desmin + cells. Major TNC-related molecular pathways were not up- or down-regulated in TNC-deficient lungs as compared to WT; only minor changes in TLR4 and TGFβR3 mRNA expression were observed. In conclusion, TNC-deficient lungs at 18 months of age showed exaggerated features of the normal structural lung aging described to occur in mice between 12 and 18 months of age. Correlated to the increased pulmonary function parameters previously observed in young adult TNC-deficient lungs and described to occur in normal lung aging between 3 and 6 months of age, TNC might be an advantage in lung aging.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1545
Author(s):  
Stephanie Arndt ◽  
Petra Unger ◽  
Anja-Katrin Bosserhoff ◽  
Mark Berneburg ◽  
Sigrid Karrer

Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts (hNF), human TGF-β-activated fibroblasts (hAF), and human localized scleroderma-derived fibroblasts (hLSF) after direct CAP treatment, co-cultured with plasma-treated human epidermal keratinocytes (hEK) and with an experimental murine model of scleroderma. In hAF and hLSF, 2 min CAP treatment with the MicroPlaSterβ® plasma torch did not affect pro-fibrotic gene expression of alpha smooth muscle actin, fibroblast activating protein, and collagen type I, however, it promoted re-expression of matrix metalloproteinase 1. Functionally, CAP treatment reduced cell migration and stress fiber formation in hAF and hLSF. The relevance of CAP treatment was confirmed in an in vivo model of bleomycin-induced dermal fibrosis. In this model, CAP-treated mice showed significantly reduced dermal thickness and collagen deposition as well as a decrease in both alpha smooth muscle actin-positive myofibroblasts and CD68-positive macrophages in the affected skin in comparison to untreated fibrotic tissue. In conclusion, this study provides the first evidence for the successful use of CAP for treating LS and may be the basis for clinical trials including patients with LS.


2021 ◽  
pp. neurintsurg-2021-017872
Author(s):  
Chao Wang ◽  
Mengxing Li ◽  
Huiyuan Chen ◽  
Xinjian Yang ◽  
Ying Zhang ◽  
...  

BackgroundAneurysm recurrence after coil embolization remains a challenging problem.ObjectiveTo determine the histopathological features of recurrent aneurysm specimens and explore the mechanism of aneurysm recurrence.MethodsNine aneurysm specimens were collected from eight patients who underwent clipping for aneurysm recurrence within 2 years after embolization. All specimens were sectioned and embedded in resin, stained with hematoxylin-eosin (H&E), Masson stain, and immunohistochemical staining for smooth muscle actin (SMA) and CD68+ antibodies, and were examined under light microscopy.ResultsFive aneurysms were surgically clipped owing to post-embolic subarachnoid hemorrhage, while the other four aneurysms had dangerous recanalization detected on follow-up imaging. Five aneurysms had self-growth and four aneurysms had coil compactions. Gross observation showed that each recurrent aneurysm was wrapped by a thrombus and the aneurysm wall; some coils protruded from the pseudocapsule in some ruptured aneurysms. Microscopically, H&E staining showed that three types of thrombi (fresh thrombus, granulation tissue, and scar tissue) coexisted in one section. In addition, characteristic unstable and unorganized thrombi with empty spaces were found in the neck cavity. Immunohistochemical staining showed that the SMA stain was discontinued and incomplete, and CD68+ antibody and H&E staining revealed inflammatory infiltrate in the aneurysm wall.ConclusionThe coexistence of three types of thrombi is the main characteristic of recurrent aneurysms. The formation of stable thrombus may be one of the key points of aneurysm recurrence. Smooth muscle cell damage and infiltration of inflammatory cells in the aneurysm wall probably contribute to the recanalization.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258802
Author(s):  
Mohammad Alabduljabbar ◽  
Diego Strianese ◽  
Osama Al-Sheikh ◽  
Hind M. Alkatan ◽  
Hailah Al-Hussain ◽  
...  

To evaluate and compare the clinical and histopathological profile of primary and recurrent orbital-periorbital plexiform neurofibromas (OPPN) in patients with neurofibromatosis type 1. We retrospectively evaluated 43 primary or recurrent neurofibroma (NF) specimens from 26 patients (2002 to 2018) at the King Khaled Eye Specialist Hospital, Saudi Arabia. Demographics, clinical presentation, and surgical intervention data were collected. Histopathological specimens were studied with hematoxylin-eosin, Alcian blue, and immunohistochemical markers; S-100, CD44, CD117, smooth muscle actin (SMA), neurofilament, and Ki-67. Of the 43 NFs specimens, 20 were primary and 23 recurrent tumors. For primary NF, the ratio of plexiform to the diffuse type was 13:7, however in recurrent tumors was 3:8 after the first recurrence, and 1:5 after multiple recurrences. Of the 17 patients with primary tumors that had paired recurrent tumors, 12/17 (70.6%) primary NFs were plexiform and 5/17 (29.4%) were diffuse. However, when tumors recurred, 13/17 tumors (76.5%) were diffuse and only 4/17 tumors (23.5%) had a plexiform pattern. The odds of a tumor having a diffuse pattern in recurrent NF was significantly higher than the plexiform pattern [OR = 7.8 (95% confidence interval 1.69:36.1) P = 0.008]. Primary plexiform NFs underwent an excision at a significantly younger age than the diffuse type. Recurrent NFs had significantly higher CD44, CD117, and neurofilament labeling (P = 0.02, P = 0.01 and P<0.001 respectively) but had significantly decreased Alcian blue, and S-100 labeling (P = 0.03, and P = 0.02 respectively) compared to primary tumors. SMA and Ki-67 proliferation index were not different between primary and recurrent NFs (P = 0.86, and P = 0.3 respectively). There appears to be a high risk for primary plexiform NFs to develop a diffuse histologic pattern when they recur. Immunohistochemical staining suggests a role of mast cells (CD117) and expression of infiltration makers (CD44) in the transformation of plexiform tumors to the diffuse phenotype.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1547
Author(s):  
Doris H. Rosero Salazar ◽  
René E. M. van Rheden ◽  
Manon van Hulzen ◽  
Paola L. Carvajal Monroy ◽  
Frank A. D. T. G. Wagener ◽  
...  

This study aimed to analyze the effects of fibrin constructs enhanced with laminin-nidogen, implanted in the wounded rat soft palate. Fibrin constructs with and without laminin-nidogen were implanted in 1 mm excisional wounds in the soft palate of 9-week-old rats and compared with the wounded soft palate without implantation. Collagen deposition and myofiber formation were analyzed at days 3, 7, 28 and 56 after wounding by histochemistry. In addition, immune staining was performed for a-smooth muscle actin (a-SMA), myosin heavy chain (MyHC) and paired homeobox protein 7 (Pax7). At day 56, collagen areas were smaller in both implant groups (31.25 ± 7.73% fibrin only and 21.11 ± 6.06% fibrin with laminin-nidogen)) compared to the empty wounds (38.25 ± 8.89%, p < 0.05). Moreover, the collagen area in the fibrin with laminin-nidogen group was smaller than in the fibrin only group (p ˂ 0.05). The areas of myofiber formation in the fibrin only group (31.77 ± 10.81%) and fibrin with laminin-nidogen group (43.13 ± 10.39%) were larger than in the empty wounds (28.10 ± 11.68%, p ˂ 0.05). Fibrin-based constructs with laminin-nidogen reduce fibrosis and improve muscle regeneration in the wounded soft palate. This is a promising strategy to enhance cleft soft palate repair and other severe muscle injuries.


2021 ◽  
Vol 15 (1) ◽  
pp. 36-42
Author(s):  
S. V. Lukyanov ◽  
K. M. Blikyan ◽  
S. S. Todorov ◽  
V. Y. Deribas ◽  
N. S. Lukyanov

Adrenal leiomyosarcoma — rare mesenchymal tumor, which is diagnosed most often after it reaches a large size. Primary adrenal leiomyosarcoma is extremely rare: in the English-language literature, only 45 cases were previously reported. We report the case of a 46-year-old man with the formation of the right adrenal gland measuring 12x8x7,5 cm. The patient underwent right-sided adrenalectomy, nephrectomy, and plastic of the inferior vena cava. The phenotype was confirmed by light microscopy and immunohistochemistry. Microscopic examination of the tumor is represented by fusiform and polymorphic cells that form multidirectional bundle structures with a high rate of mitosis. Immunohistochemically, tumor cells were positive for smooth muscle actin, CD-34, CD-117.


2021 ◽  
Author(s):  
Xiao Wei ◽  
Attigah S. D. Kwasi ◽  
Qi Li ◽  
Hongyan Wu ◽  
Jun Chen ◽  
...  

Abstract Background: Plexiform fibromyxoma (PF) is a very rare mesenchymal tumor of the stomach. Here we report one case of this unusual gastric tumor that was pathologically confirmed after endoscopic resection. Its clinical and pathologic features were observed while the relevant literature was reviewed. Case presentation: A 1.0 cm round elevated submucosal mass was discovered by gastroscopy in a 44-year-old Chinese woman due to recurrent abdominal pain. The tumor was characterized by a multinodular plexiform pattern, bland-looking oval to spindle cells, and a myxoid stroma with thin arborizing capillaries. Immunohistochemistry analysis revealed that the tumor cells were positive for smooth muscle actin (SMA) and negative for CD117, DOG-1, CD34, Desmin, progesterone receptor (PR), CD10, S100 and SOX10. A diagnosis of PF was rendered.Conclusion: Gastric PF is a benign tumor without evidence of local recurrence and distant metastasis. This case emphasizes the unique histological appearance and immunophenotype of PF to promote early diagnosis, while endoscopic resection can be used as an alternative treatment for small and superficial PF.


2021 ◽  
Vol 11 (12) ◽  
pp. 2329-2336
Author(s):  
Qiang Zeng ◽  
Yiting Luo

In order to explore effects of long-chain non-coding ribonucleic acid (RNA) HOTAIR on proliferation and migration of human lens epithelial cells, SRA01/04 cells were selected as the research strain in this study and divided into S1 group (no HOTAIR transfection), S2 group (siHOTAIR transfection), S3 group (siHOTAIR+10 ng/mL TGF-β2), and S4 group (no HOTAIR transfection+10 ng/mL TGF-β2) according to the presence or absence of transforming growth factor (TGF)-β2 and silent HOTAIR treatment. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric method was applied to detect cell proliferation.Western blot was used for detection of E-cadherin, zonula occluden-1 (ZO-1), Vimentin, α-smooth muscle actin (SMA), Snail, Slug, zinc finger E-box binding homeobox 1 (ZEB1), and Smad-2 expressions. Results showed that the number of transmembrane cells in S4 group was higher markedly than that of the other groups, but that of S2 group dropped steeply compared with the other groups (P <0.05); E-cadherin (2.59±0.58) and ZO-1 (1.95±0.56) of S2 group increased hugely compared with the other groups, while Vimentin (0.57±0.14) and α-SMA (0.64±0.28) decreased sharply compared with the other groups (P < 0.05); Snail (2.51±0.59), Slug (2.11±0.47), and ZEB1 (2.83±0.53) of S4 group rose obviously compared with the other groups, but the above of S2 group reduced hugely compared with the other groups (P < 0.05); pSmad-2 and pSmad-3 of S4 group elevated greatly compared with the other groups, and those of S2 group reduced hugely compared with the other groups (P < 0.05). In conclusion, HOTAIR high expression could promote TGF-β2-induced SRA01/04 cell proliferation, migration, invasion, and epithelial-mesenchymal trans-differentiation, which was related to TGF-β/Smad signaling pathway.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giuseppina Abignano ◽  
Heidi Hermes ◽  
Sonsoles Piera-Velazquez ◽  
Sankar Addya ◽  
Francesco Del Galdo ◽  
...  

AbstractMyofibroblasts are the key effector cells responsible for the exaggerated tissue fibrosis in Systemic Sclerosis (SSc). Despite their importance to SSc pathogenesis, the specific transcriptome of SSc myofibroblasts has not been described. The purpose of this study was to identify transcriptome differences between SSc myofibroblasts and non-myofibroblastic cells. Alpha smooth muscle actin (α-SMA) expressing myofibroblasts and α-SMA negative cells were isolated employing laser capture microdissection from dermal cell cultures from four patients with diffuse SSc of recent onset. Total mRNA was extracted from both cell populations, amplified and analyzed employing microarrays. Results for specific genes were validated by Western blots and by immunohistochemistry. Transcriptome analysis revealed 97 differentially expressed transcripts in SSc myofibroblasts compared with non-myofibroblasts. Annotation clustering of the SSc myofibroblast-specific transcripts failed to show a TGF-β signature. The most represented transcripts corresponded to several different genes from the Neuroblastoma Breakpoint Family (NBPF) of genes. NBPF genes are highly expanded in humans but are not present in murine or rat genomes. In vitro studies employing cultured SSc dermal fibroblasts and immunohistochemistry of affected SSc skin confirmed increased NBPF expression in SSc. These results indicate that SSc myofibroblasts represent a unique cell lineage expressing a specific transcriptome that includes very high levels of transcripts corresponding to numerous NBPF genes. Elevated expression of NBPF genes in SSc myofibroblasts suggests that NBPF gene products may play a role in SSc pathogenesis and may represent a novel therapeutic target.


2021 ◽  
pp. 109352662110469
Author(s):  
Paola X. De la Iglesia Niveyro ◽  
J. Pandolfi ◽  
F. Jauk ◽  
T. Kreindel ◽  
P. Lobos

We present a 29-month-old male patient in follow-up due to pyelocaliceal dilation with a prostatic nodule incidentally found during ultrasound evaluation. Cysto video endoscopy was performed and a prostate biopsy, obtained. Microscopic evaluation showed a haphazardly distributed population of muscular cells with cross striations without evidence of mitosis or necrosis. Immunohistochemistry was positive for myogenin and desmin and negative for smooth muscle actin. Next generation sequencing was performed without finding any pathogenic variant or fusion in the tumor RNA. The patient received no further treatment, remained asymptomatic and continues in follow up, 3 years after initial diagnosis. We report a case of prostate rhabdomyoma in a toddler, an exceptional location that raises concern about differential diagnosis with its malignant counterpart, rhabdomyosarcoma, especially at this age.


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