Membrane Tissue Research Articles

Protective efficacy of dietary natural antioxidants on microplastic particles-induced histopathological lesions in African catfish (Clarias gariepinus)

Microplastic particles (MPs) are a common environmental pollutant easily ingested by fish in aquaculture. The current study evaluated the protective efficacies of some antioxidant, e.g., lycopene, citric acid, and chlorella, against the toxic effects of MP ingestion by Clarias gariepinus using histopathological biomarkers. Five experimental groups were established, a control group receiving only a standard diet, a group exposed to 500 mg/kg MP concomitant with the standard diet, and three antioxidant groups exposed to MPs plus either lycopene (500 mg/kg), citric acid (30 g/kg), or chlorella (50 g/kg) in the standard diet. After 15 days, fish were sacrificed for histological and histochemical examinations. Histological analysis of the kidney for group 2 (fed 500 mg/kg MPs alone) revealed distributed tissue dissociation, regional glomerular hypertrophy or shrinkage, melanomacrophage accumulation, and expansion of Bowman’s space, while liver tissue exhibited dilation and rupture of the central vein wall, hemorrhage, cytoplasmic vacuolation, and cellular necrosis or apoptosis. Fish exposed to MPs also exhibited connective tissue fiber accumulation around renal blood vessels, renal tubules, the central hepatic vein, hepatic blood sinusoids, and serosal, muscle, and submucosal layers of the intestine. In addition, MP exposure reduced carbohydrate (mainly glycogen) contents in the brush borders and basement membranes of renal tubules, glomeruli, and intestinal tissues as well as in the cytoplasm of hepatocytes. These signs of renal, hepatic, and intestinal histopathology were fully or partially reversed by dietary lycopene, chlorella, or citric acid. Enhancing dietary antioxidants is an effective strategy for preventing MP toxicity in Clarias gariepinus in aquaculture.

Long Hanging Structure of Collagen VII Connects the Elastic Fibers and the Basement Membrane in Young Skin Tissue.

Aging leads to substantial structural changes in the skin. Elastic fibers maintain skin structure, but their degeneration and loss of function with age result in wrinkle formation and loss of skin elasticity. Oxytalan fiber, a type of elastic fiber, extends close to the dermal-epidermal junction (DEJ) from the back of the dermis. Oxytalan fibers are abundant in the papillary layer and contribute to skin elasticity and texture. However, to accurately understand the mechanisms of skin elasticity, the interaction between elastic fibers and DEJ should be elucidated. Here, we investigated elastic fibers and DEJ and their structural alterations with aging. Several basement membrane proteins [collagen (COL) IV, COLVII, and laminin 332], fibrous tropoelastin, and fibrillin-1 in excised human skin tissue were observed using three-dimensional imaging. Age-related alterations in COLVII, elastic fibers, and fibrillin-1 were evaluated. We found that COLVII forms long hanging structures and is co-localized with fibrous tropoelastin in young skin but not aged skin. Fibrillin-1-rich regions were observed at the tips of elastin fibers in young skin tissue, but rarely in aged skin. This co-localization of elastic fiber and COLVII may maintain skin structure, thereby preventing wrinkling and sagging. COLVII is a potential therapeutic target for skin wrinkling.

Water lily appearance synonymous with hydatid cyst

The water lily appearance corresponds to the presence of wavy or serpiginous structures within an excavated mass. It indicates the presence of a complicated hydatid cyst. Hydatid cyst is a cosmopolitan anthropozoonosis, related to the development of a larval form of a parasite "echinococcus granulosis". The pulmonary localization comes in second place after the hepatic one [1]. From an anatomical point of view, a hydatid cyst appears to be made up of a reactionary tissue membrane belonging to the host and two other membranes, constituents of the parasite; one is acellular (anhistic cuticle) whereas the second, the germinative proliga, gives rise to daughter vesicles. It contains hydatid fluid in rock water containing numerous protoscolex and membrane debris known as hydatid sand [2]. It is suspected in the presence of hemoptysis, rejection of membranes, hydatid vomitus or non-specific respiratory symptoms concomitant with a particular context in this case when contact with dogs, which are the definitive hosts, is found. Its diagnosis is made possible by imaging through chest X-ray and thoracic CT, which are by far the most used means. Thus, different aspects of hydatid cysts are found on imaging, depending on the stage of evolution: it may be a simple cyst (unilocular cyst), identified as a low-toned, watery, well-limited, homogeneous opacity, known as a cannonball; corresponding to a mass of liquid density with a thin, regular wall on CT; or a complicated cyst (fissuring, rupture, compression). In the case of rupture, the hydatid cyst appears as a hydroaerobic image with an undulating border, describing serpentine structures, reminiscent of a "water lily" flower [1]. This sign is of great help in the etiological research in front of a hydro-pneumothorax of great abundance, thus implying a surgical management.

Functional Ultrastructure of Hymenopteran Stingers: Devastating Spear or Delicate Syringe.

In this study, we tested the hypothesis that a micro-serrated edge on the honey bee Apis mellifera stinger tip serves as a tool for more intensive crushing of cell membranes in the victim's tissues. This could have mechanical consequences as well as initiate metabolic pathways linked to cell membrane breakdown (e.g., production of biogenic amines). Accordingly, we found that hymenopteran species that use their stingers as an offensive or defensive weapon to do as much damage to the victim's body as possible had this cuticular microstructure. In parasitic hymenopterans, on the other hand, this structure was missing, as stingers are solely used to delicately transport venom to the victim's body in order to do little mechanical harm. We also demonstrated that the stinger lancets of the honey bee A. mellifera are living organs with sensilla innervated by sensory neurons and containing other essential tissues, rather than mere cuticular structures.

Катіонні канали – молекулярні мішені для потенційних лікарських засобів з анальгетичним механізмом дії

Ion channels ensure the functioning of the nervous system because they are involved in the depolarization of neurons, axonal conduction and the release of neurotransmitters. They are located in the membranes of all excitable tissues and are involved in the mechanisms of nociception. Modulation of ion channel signaling by small molecules can be effective in inhibiting the course of pain syndromes of various etiologies. A small number of ion channels are currently identified as potential targets for the development of antinociceptive drugs, as evidenced by medicinal chemistry data and various biophysical and pharmacological studies. This review provides examples of selective cation channel modulators as novel therapeutic agents for analgesia and prospects for the creation of innovative channel-targeted analgesic drugs.

THICKNESS OF THE CORACOHUMERAL LIGAMENT IN CASES OF RECURRENT SHOULDER DISLOCATION

Enhancement of the joint capsule, fibrovascular tissue, and synovial membrane in the rotator cuff interval using MRI can aid the identification of adhesive capsulitis following intravenous gadolinium injection. This study assesses the thickness of the coracohumeral ligament (CHL) in the cases of recurrent shoulder dislocation and identifies the status of the CHL in these cases. A 3T MRI machine was used to perform the imaging. Patients were included with a history of at least two episodes of shoulder dislocation at the radiology department of King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, from January 2017 to May 2020. A total of 177 patients were diagnosed with recurrent shoulder dislocation through its associated symptoms, out of which 107 had a history of shoulder dislocation. A mean CHL thickness was reported in the control group as 1.6 (± 0.49) mm, while in patients with shoulder dislocation it was reported as 2.84 (± 0.91) mm. A statistically significant relationship was observed between CHL thickness and the presence of Hill-Sachs and Bankart lesions. The study concluded that increased CHL thickness is strongly correlated with shoulder dislocation: there is a good predictability of shoulder dislocation based on the presence of thickened CHL.

Metabolic management of microenvironment acidity in glioblastoma.

Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.

Tactics for treating young children with pyelonephritis and vesicoureteral reflux associated with impaired fibrillogenesis.

The purpose of this study is to substantiate the choice and evaluate the effectiveness of therapeutic tactics aimed at suppressing collagen formation and improving metabolic processes in the kidney parenchyma in young children with pyelonephritis against the background of vesicoureteral reflux associated with undifferentiated tissue dysfunction. 67 children from 2weeks to 3years old with pyelonephritis and vesicoureteral reflux were examined. All children during the period of remission of the inflammatory process were examined for the content of oxyproline in the urine. Urine crystallinity and urinary excretion were determined, and markers of the morphofunctional state of the cytomembranes of the renal epithelium were determined: calcification test-the presence of polar lipids in the urine and test for the presence of lipid peroxidation products in the urine. Children with high urinary hydroxyproline excretion prior to protocol treatment of pyelonephritis during the remission of the inflammatory process at the stage of maintenance therapy were recommended to receive metabolic preparations that can inhibit collagen formation and improve parenchyma metabolic processes during the month-vitamin E 10% and L-carnitine in age-related doses. After 6months, a study was made on the functional state of the renal parenchyma in the dynamics of treatment. After metabolic antihypoxic and membrane-protective therapy, there was a significant positive dynamic of all markers of tissue hypoxia and membrane destruction in the kidney parenchyma, which confirms the inhibition of collagen formation processes and a decrease in tissue hypoxia with vitamin E and L-carnitine in age-related doses.

Protective Role of Mitochondrial Uncoupling Proteins against Age-Related Oxidative Stress in Type 2 Diabetes Mellitus.

The accumulation of oxidative damage to DNA and other biomolecules plays an important role in the etiology of aging and age-related diseases such as type 2 diabetes mellitus (T2D), atherosclerosis, and neurodegenerative disorders. Mitochondrial DNA (mtDNA) is especially sensitive to oxidative stress. Mitochondrial dysfunction resulting from the accumulation of mtDNA damage impairs normal cellular function and leads to a bioenergetic crisis that accelerates aging and associated diseases. Age-related mitochondrial dysfunction decreases ATP production, which directly affects insulin secretion by pancreatic beta cells and triggers the gradual development of the chronic metabolic dysfunction that characterizes T2D. At the same time, decreased glucose oxidation in skeletal muscle due to mitochondrial damage leads to prolonged postprandial blood glucose rise, which further worsens glucose homeostasis. ROS are not only highly reactive by-products of mitochondrial respiration capable of oxidizing DNA, proteins, and lipids but can also function as signaling and effector molecules in cell membranes mediating signal transduction and inflammation. Mitochondrial uncoupling proteins (UCPs) located in the inner mitochondrial membrane of various tissues can be activated by ROS to protect cells from mitochondrial damage. Mitochondrial UCPs facilitate the reflux of protons from the mitochondrial intermembrane space into the matrix, thereby dissipating the proton gradient required for oxidative phosphorylation. There are five known isoforms (UCP1-UCP5) of mitochondrial UCPs. UCP1 can indirectly reduce ROS formation by increasing glutathione levels, thermogenesis, and energy expenditure. In contrast, UCP2 and UCP3 regulate fatty acid metabolism and insulin secretion by beta cells and modulate insulin sensitivity. Understanding the functions of UCPs may play a critical role in developing pharmacological strategies to combat T2D. This review summarizes the current knowledge on the protective role of various UCP homologs against age-related oxidative stress in T2D.

LB962 Barrier integrity test for in vitro permeation testing of topical and transdermal products

In vitro skin permeation testing (IVPT) is often used to ensure sufficient efficacy of dermaceuticals. IVPT studies utilize viable tissue membrane to represent in vivo conditions. The intact barrier of such tissue membrane provides biological relevance, in vitro. Transepidermal water loss (TEWL) measures changes in water vapor density on the skin surface. The purpose of this study was to evaluate TEWL as an appropriate barrier integrity test, in vitro, and determine an acceptable range using a Delfin® Vapometer.

Effect of Different Membranes on Vertical Bone Regeneration: A Systematic Review and Network Meta-Analysis.

This study is aimed at performing a systematic review and a network meta-analysis of the effects of several membranes on vertical bone regeneration and clinical complications in guided bone regeneration (GBR) or guided tissue regeneration (GTR). We compared the effects of the following membranes: high-density polytetrafluoroethylene (d-PTFE), expanded polytetrafluoroethylene (e-PTFE), crosslinked collagen membrane (CCM), noncrosslinked collagen membrane (CM), titanium mesh (TM), titanium mesh plus noncrosslinked (TM + CM), titanium mesh plus crosslinked (TM + CCM), titanium-reinforced d-PTFE, titanium-reinforced e-PTFE, polylactic acid (PLA), polyethylene glycol (PEG), and polylactic acid 910 (PLA910). Using the PICOS principles to help determine inclusion criteria, articles are collected using PubMed, Web of Science, and other databases. Assess the risk of deviation and the quality of evidence using the Cochrane Evaluation Manual, and GRADE. 27 articles were finally included. 19 articles were included in a network meta-analysis with vertical bone increment as an outcome measure. The network meta-analysis includes network diagrams, paired-comparison forest diagrams, funnel diagrams, surface under the cumulative ranking curve (SUCRA) diagrams, and sensitivity analysis diagrams. SUCRA indicated that titanium-reinforced d-PTFE exhibited the highest vertical bone increment effect. Meanwhile, we analyzed the complications of 19 studies and found that soft tissue injury and membrane exposure were the most common complications.

Extracellular DNA in blood: an index of <i>in vivo</i> inflammatory response

Increased concentration of cell-free DNA (cfDNA) in the circulating blood of humans and animals is a sign of inflammatory conditions and a distinctive characteristic of various pathophysiological processes in the body. The aim of the present study was to investigate the possible role of tumor necrosis factor (TNFα) in changes of cfDNA contents in peripheral blood as a response to experimentally induced systemic inflammation.We used 40 female hybrid mice (C57Bl/6xDBA/2) F1 at the age of 6-8 weeks. The concentration of cfDNA and its individual fractions was determined using a PicoGreen fluorescent dye. The dynamics of inflammatory process was evaluated after 4, 8, 11 and 24 hours following LPS injection. A significant increase in the blood plasma cfDNA levels was shown under the action of E. coli lipopolysaccharide (LPS), along with simultaneous decreased levels of cfDNA, associated with cell surface. The ratio of cell surface-bound cfDNA to the total cfDNA contents was reduced in dose-dependent manner as early as 4 hours after LPS injection to the animals, thus allowing us to consider this ratio a characteristic sign of netosis of neutrophilic granulocytes during the development of acute inflammation. The described effects are significantly suppressed with co-injection of recombinant TNFα neutralizing protein along with LPS, whereas increased intake of neutrophils in the tissues is determined by some other factors which are not directly related to the production of this cytokine.Based on the obtained data, we proposed a following hypothesis: induction of netosis by inflammatory stimuli causes an increase in the concentration of cfDNA in blood plasma not only due to de novo emerging extracellular DNA by neutrophil netosis, but also by the release of distinct cfDNA fraction that was previously firmly bound to cell membranes in multiple body tissues under the action of proteases released during netosis.

Biomimicking design of artificial periosteum for promoting bone healing.

BackgroundPeriosteum is a vascularized tissue membrane covering the bone surface and plays a decisive role in bone reconstruction process after fracture. Various artificial periosteum has been developed to assist the allografts or bionic bone scaffolds in accelerating bone healing. Recently, the biomimicking design of artificial periosteum has attracted increasing attention due to the recapitulation of the natural extracellular microenvironment of the periosteum and has presented unique capacity to modulate the cell fates and ultimately enhance the bone formation and improve neovascularization.MethodsA systematic literature search is performed and relevant findings in biomimicking design of artificial periosteum have been reviewed and cited.ResultsWe give a systematical overview of current development of biomimicking design of artificial periosteum. We first summarize the universal strategies for designing biomimicking artificial periosteum including biochemical biomimicry and biophysical biomimicry aspects. We then discuss three types of novel versatile biomimicking artificial periosteum including physical-chemical combined artificial periosteum, heterogeneous structured biomimicking periosteum, and healing phase-targeting biomimicking periosteum. Finally, we comment on the potential implications and prospects in the future design of biomimicking artificial periosteum.ConclusionThis review summarizes the preparation strategies of biomimicking artificial periosteum in recent years with a discussion of material selection, animal model adoption, biophysical and biochemical cues to regulate the cell fates as well as three types of latest developed versatile biomimicking artificial periosteum. In future, integration of innervation, osteochondral regeneration, and osteoimmunomodulation, should be taken into consideration when fabricating multifunctional artificial periosteum.The Translational Potential of this Article: This study provides a holistic view on the design strategy and the therapeutic potential of biomimicking artificial periosteum to promote bone healing. It is hoped to open a new avenue of artificial periosteum design with biomimicking considerations and reposition of the current strategy for accelerated bone healing.

MG53 preserves mitochondrial integrity of cardiomyocytes during ischemia reperfusion-induced oxidative stress

Ischemic injury to the heart induces mitochondrial dysfunction due to increasing oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle, is secreted as a myokine after exercise, and is essential for repairing damaged plasma membrane of many tissues by interacting with the membrane lipid phosphatidylserine (PS). We hypothesized MG53 could preserve mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondria protection to prevent mitophagy. Fluorescent imaging and Western blotting experiments showed recombinant human MG53 (rhMG53) translocated to the mitochondria after ischemic injury in vivo and in vitro. Fluorescent imaging indicated rhMG53 treatment reduced superoxide generation in ex vivo and in vitro models. Lipid-binding assay indicated MG53 binds to CL. Transfecting cardiomyocytes with the mitochondria-targeted mt-mKeima showed inhibition of mitophagy after MG53 treatment. Overall, we show that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53's interactions with mitochondria could be an attractive avenue for developing MG53 as a targeted protein therapy for cardioprotection.

Interaction of multiple spiral rotors in a reaction-diffusion system.

Rotors of reaction and diffusion are phase singularities that give rise to spiral waves of chemical activity, which are very similar to spatiotemporal patterns observed across several excitable media. Here we carry out experiments with the Belousov-Zhabotinsky reaction system and numerical simulations based on a reaction-diffusion model to show the possible interactions of multiple spiral rotors. When the cores of two spirals come very close to each other, they could either repel, attract, or remain stationary, depending on their relative chirality, phase, and distance separating them. Multiple pairs of spiral waves, in proximity to each other, could alter the paths of the individual rotors. A spiral core will be influenced most by the rotor that is closest to it, depending on the nature of the corresponding spiral wave arm. We observed rotors lying within a limiting distance of each other attract and annihilate. Otherwise, they push each other away until they reach a critical distance, beyond which all interactions seem to cease. We have established a relationship of this critical distance to the properties of the spiral wave. We also observed spontaneous symmetry-breaking instability for a system of up to eight rotors. Our experiments with the Belousov-Zhabotinsky reaction have successfully demonstrated the validity of the numerical results. A thorough understanding of the dynamics of several spiral rotors within a small area could help us perceive the nature of such excitation waves in cardiac tissue and cell membranes.

Detection of immune‐related enzyme activity, gene expression and metabolomic profiling in Chinese mitten crab Eriocheir sinensis parasitized by Polyascus gregaria

Polyascus gregaria is a specialized crustacean parasite of Chinese mitten crab; however, only limited information on interactions between parasite and its host is available. This study examined interactions between P. gregaria and Chinese mitten crab with regard to immune-related enzyme activities and expression of respective genes in the hepatopancreas. To further elucidate the pathogen–host interactions, untargeted gas chromatography–mass spectrometry (GC–MS) metabolomics was used to analyse changes in metabolites in response to P. gregaria infection. Superoxide dismutase, acid phosphatase and alkaline phosphatase activities were significantly increased in parasitized crabs, whereas phenoloxidase activity was significantly decreased. Moreover, the expression of three immune-related genes, that is proPO, Toll1 and Toll2, was markedly downregulated in parasitized crabs. In the metabolomic assay, 73 differential metabolites were identified, and they were significantly enriched in 71 pathways. Among these metabolites, 58 were significantly upregulated and 15 were downregulated. Lysolipids lysoPE, lysoPC, lysoPG, LysoPI and lysoPS were the most strongly upregulated metabolites, and 9-cis-retinol, glycerophosphocholine and 5-thymidylic acid were the top three downregulated metabolites. Most of these metabolites were enriched in the glycerophospholipid metabolism pathway, which was one of the most significantly activated pathway responses to P. gregaria infection. This increase in lysoglycerophospholipids caused major structural and functional abnormalities in the membranes of host tissues, especially in the hepatopancreas. We propose that long-term infection with P. gregaria induces silence of the innate immune system, disturbs intracellular homeostasis and causes cell membrane immune-related dysfunction in Chinese mitten crab. These results may help us better understand P. gregaria infection in Chinese mitten crab.

Differentiation of Mesenchymal Stem Cells Derived from Amniotic Membrane to Neuronal Cells and the Expression of PAX2 and NURR1 Genes

: Mesenchymal stem cells (MSCs) have different sources, including bone marrow, adipose tissue, umbilical cord, amniotic fluid, and amniotic membrane. They have immunomodulatory properties. These cells can be used for the treatment of many neurological diseases such as Parkinson’s and Alzheimer’s disease. In this study, MSCs were isolated from the amniotic membrane, and their surface markers were investigated using flow cytometry. MSCs were differentiated to osteoblasts, adipocytes, and finally, to the nerve cells under the influence of epidermal, basic fibroblast natural growth factors, and two other media. The first medium included indomethacin, butyric acid, and ascorbic acid. The second one included retinoic acid and ascorbic acid. The expression of paired box gene 2 (PAX2) and nuclear receptor related-1 (NURR1) genes were investigated using real-time polymerase chain reaction and showed higher levels than that of controls. The presence of the expression of β-tubulin III and microtubule-associated protein 2 (MAPII) was studied by immunocytochemistry. The result suggested that the second medium included retinoic acid was better than the first medium. Protecting neurons are important in neurological diseases, and the expression of mRNAs such as PAX2, NURR1, β-tubulin III, and MAPII plays an effective role in neural differentiation.

Use of an Endoloop Ligature and a 2-Portal Coelioscopic Approach for the Removal of an Arrowhead Foreign Body in a Red-Tailed Hawk (Buteo jamaicensis).

A juvenile red-tailed hawk (Buteo jamaicensis) was presented to the Ontario Veterinary College from a wildlife rehabilitation facility for the assessment of an arrowhead foreign body injury. The hawk was found on the ground with the left wing in a dropped position. Radiographic images revealed an arrowhead foreign body superimposed over the left lung and thoracic air sacs, immediately medial to the ribs on the ventrodorsal view, and ventral to the scapulae on the right latero-lateral view. A coelioscopy was performed using a left lateral approach with a 2.7-mm rigid endoscope into the left caudal thoracic air sac, with an additional instrument port through the left abdominal air sac. The arrowhead was visualized adjacent to the left lung, separated from the cranial thoracic air sac cavity by a membrane of fibrous tissue. The tissue membrane was radiosurgically incised. Forceps were then used to guide an Endoloop around the arrowhead. The arrowhead was secured by tightening the Endoloop, and the body wall incision was extended to facilitate the arrowhead extraction.

Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.

Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.

Mechanical Interaction of the Pericardium and Cardiac Function in the Normal and Hypertensive Rat Heart.

The pericardium is a thin connective tissue membrane that surrounds the heart and is an integral regulatory component of cardiopulmonary performance. Pathological growth and remodeling of the right ventricle (RV) stemming from structural heart diseases are thought to include a significant role of the pericardium, but its exact role remains unclear. The objective of this study was to investigate potential biomechanical adaptations of the pericardium in response to pulmonary hypertension and their effects on heart behavior. Integrated computational-experimental modeling of the heart offers a robust platform to achieve this objective. We built upon our recently developed high-fidelity finite-element models of healthy and hypertensive rodent hearts via addition of the pericardial sac. In-silico experiments were performed to investigate changes in pericardium reserve elasticity and their effects on cardiac function in hypertensive hearts. Our results suggest that contractile forces would need to increase in the RV and decrease in the left ventricle (LV) in the hypertensive heart to compensate for reductions in pericardium reserve elasticity. The discrepancies between chamber responses to pericardium addition result, in part, from differences in the impact of pericardium on the RV and LV preload. We further demonstrated the capability of our platform to predict the effect of pericardiectomy on heart function. Consistent with previous results, the effect of pericardiectomy on the chamber pressure-volume loop was the largest in the hypertensive RV. These insights are expected to motivate further computational investigations of the effect of pericardiectomy on cardiac function which remains an important factor in surgical planning of constrictive pericarditis and coronary artery bypass grafting.