Extracellular Connective Tissue Research Articles

Корекція пробіотиком пародонтального синдрому у тварин за умов ожиріння і хронічного стресу

The aim of this study was to investigate the effect of obesity and chronic stress on periodontal tissues, both separately and in the combined comorbidity of these conditions in rats, and the role of the probiotic Lactobacillus casei in the correction of periodontal syndrome under these conditions. Methods. The development of periodontal syndrome and the effectiveness of the probiotic Lactobacillus casei IMV B-7280, administered to rats from one month of age intragastrically in a volume of 1 mL (5 · 108 CFU) in two-week courses with breaks of 2 weeks, were studied in a model of glutamate-induced obesity and chronic stress - in combination and separately. In periodontal tissues, the total proteolytic and antitryptic activity, free fucose and glycosaminoglycans (GAG) content, catalase activity, thiobarbiturate active products (TBA reagents), and the content of oxidatively modified proteins (OMP) and molecules of average mass (AMM) were determined; in bone tissue, the molar root exposure coefficient was calculated. The anthropometric parameters of the animals and the Selye triad were studied. Results. We have substantiated the development of periodontal syndrome in animals with glutamate-induced obesity against the background of chronic stress, as evidenced by the activation of free radical oxidation of lipids and proteins, depolymerization of fucoproteins and proteoglycans of periodontal connective tissue, which causes exposure of molar roots by almost 65%. The administration of the probiotic Lactobacillus casei in two-week courses with intervals of 2 weeks to obese rats with chronic stress prevented the development of obesity, as evidenced by a significant decrease in visceral fat mass, Li index, and BMI, as well as the severity of stress syndrome, as evidenced by a decrease in ulcer formation, thymus involution, and adrenal hypertrophy. The periodontoprotective effect of Lactobacillus casei under the combined influence of obesity and chronic stress was proved by significant changes in oxidative stress, free fucose, and GAG content and a 1.5-times decrease in the molar root exposure ratio. Conclusions. Periodic administration of Lactobacillus casei to rats treated with sodium glutamate in the neonatal period against the background of chronic stress prevented the development of obesity, the severity of stress syndromeб and damage to periodontal tissues, as evidenced by the prevention of oxidative stress, increased catabolism of extracellular connective tissue proteins and antiresorptive effect.

Variants in DTNA cause a mild, dominantly inherited muscular dystrophy.

DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype, but variants in DTNA have not previously been associated with human skeletal muscle disease. We present 12 individuals from four unrelated families with two different monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin. The five affected individuals from family A harbor a c.1585G > A; p.Glu529Lys variant, while the recurrent c.1567_1587del; p.Gln523_Glu529del DTNA variant was identified in the other three families (family B: four affected individuals, family C: one affected individual, and family D: two affected individuals). Myalgia and exercise intolerance, with variable ages of onset, were reported in 10 of 12 affected individuals. Proximal lower limb weakness with onset in the first decade of life was noted in three individuals. Persistent elevations of serum creatine kinase (CK) levels were detected in 11 of 12 affected individuals, 1 of whom had an episode of rhabdomyolysis at 20years of age. Autism spectrum disorder or learning disabilities were reported in four individuals with the c.1567_1587 deletion. Muscle biopsies in eight affected individuals showed mixed myopathic and dystrophic findings, characterized by fiber size variability, internalized nuclei, and slightly increased extracellular connective tissue and inflammation. Immunofluorescence analysis of biopsies from five affected individuals showed reduced α-dystrobrevin immunoreactivity and variably reduced immunoreactivity of other DGC proteins: dystrophin, α, β, δ and γ-sarcoglycans, and α and β-dystroglycans. The DTNA deletion disrupted an interaction between α-dystrobrevin and syntrophin. Specific variants in the coiled-coil domain of DTNA cause skeletal muscle disease with variable penetrance. Affected individuals show a spectrum of clinical manifestations, with severity ranging from hyperCKemia, myalgias, and exercise intolerance to childhood-onset proximal muscle weakness. Our findings expand the molecular etiologies of both muscular dystrophy and paucisymptomatic hyperCKemia, to now include monoallelic DTNA variants as a novel cause of skeletal muscle disease in humans.

The impact of collagen protein ingestion on musculoskeletal connective tissue remodeling: a narrative review.

Collagen is the central structural component of extracellular connective tissue, which provides elastic qualities to tissues. For skeletal muscle, extracellular connective tissue transmits contractile force to the tendons and bones. Connective tissue proteins are in a constant state of remodeling and have been shown to express a high level of plasticity. Dietary-protein ingestion increases muscle protein synthesis rates. High-quality, rapidly digestible proteins are generally considered the preferred protein source to maximally stimulate myofibrillar (contractile) protein synthesis rates. In contrast, recent evidence demonstrates that protein ingestion does not increase muscle connective tissue protein synthesis. The absence of an increase in muscle connective tissue protein synthesis after protein ingestion may be explained by insufficient provision of glycine and/or proline. Dietary collagen contains large amounts of glycine and proline and, therefore, has been proposed to provide the precursors required to facilitate connective tissue protein synthesis. This literature review provides a comprehensive evaluation of the current knowledge on the proposed benefits of dietary collagen consumption to stimulate connective tissue remodeling to improve health and functional performance.

Clinical Correlation of Bladder Electron Microscopic Characteristics in Patients with Detrusor Underactivity of Various Etiologies.

This study aimed to investigate the ultrastructural characteristics of the bladder of patients with detrusor underactivity (DU) of various etiologies. Twenty-five patients with DU and control subjects underwent urodynamic testing and transmission electron microscopic examination of bladder specimens. The epithelium, lamina propria, and muscle layers were analyzed separately. The DU bladders exhibited total epithelial denudation (52%). In the bladders with remaining epithelium, apical cell uroplakins (44.4%) and tight junction complexes (77.8%) were also noted. The lamina propria was characterized by loose extracellular connective tissue (48%) and a lack of nerve terminals (76%). Smooth muscle shrinkage and a loss of their regular spindle shape (91.6%) were also noted in the detrusor layer. Patients with DU with intact epithelial cell layers had significantly larger void volumes and maximal flow rates than those with mild or severe epithelial denudation. Patients with remaining nerve terminals in lamina propria had a stronger first sensation of filling and smaller residual urine volume than those without nerve terminals. The proportion of ultrastructural defects of the bladder was not significantly different among patients with DU of various etiologies and treatment outcomes. DU bladders were characterized by ultrastructural defects in the entire bladder, and the defects were correlated to clinical parameters.

A Physiology-Guided Classification of Active-Stress and Active-Strain Approaches for Continuum-Mechanical Modeling of Skeletal Muscle Tissue.

The well-established sliding filament and cross-bridge theory explain the major biophysical mechanism responsible for a skeletal muscle's active behavior on a cellular level. However, the biomechanical function of skeletal muscles on the tissue scale, which is caused by the complex interplay of muscle fibers and extracellular connective tissue, is much less understood. Mathematical models provide one possibility to investigate physiological hypotheses. Continuum-mechanical models have hereby proven themselves to be very suitable to study the biomechanical behavior of whole muscles or entire limbs. Existing continuum-mechanical skeletal muscle models use either an active-stress or an active-strain approach to phenomenologically describe the mechanical behavior of active contractions. While any macroscopic constitutive model can be judged by it's ability to accurately replicate experimental data, the evaluation of muscle-specific material descriptions is difficult as suitable data is, unfortunately, currently not available. Thus, the discussions become more philosophical rather than following rigid methodological criteria. Within this work, we provide a extensive discussion on the underlying modeling assumptions of both the active-stress and the active-strain approach in the context of existing hypotheses of skeletal muscle physiology. We conclude that the active-stress approach resolves an idealized tissue transmitting active stresses through an independent pathway. In contrast, the active-strain approach reflects an idealized tissue employing an indirect, coupled pathway for active stress transmission. Finally the physiological hypothesis that skeletal muscles exhibit redundant pathways of intramuscular stress transmission represents the basis for considering a mixed-active-stress-active-strain constitutive framework.

Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome

This case reports on a 21/2-year-old male child with GAPO syndrome, a rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Since Anderson and Pindborg in 1947 first described this syndrome, close to 30 individuals have been reported with this diagnosis. Often a history of consanguinity is noted, as in our case, in this rare autosomal recessive condition. The phenotype of this condition, initially thought to be a result of ectodermal dysplasia, can be attributed to the accumulation of extracellular connective tissue matrix and its progressive character must be pointed out. The clinical findings, ophthalmological features that include optic atrophy, glaucoma, are reviewed and discussed.

Oral and Maxillofacial Complications due to the use of Hyaluronic Acid as an Alternative for Facial Implants

This work aimed to review in the scientific literature the reported complications associated with the use of Hyaluronic Acid (HA) as an option for dermal implants in the maxillofacial region and how the health professional should intervene. The pathological and aesthetic defect restorative treatments for the human body are increasingly gaining space in several areas of health. Dentistry is one of these areas that has stood out in diseases and complications diagnosis of functional and aesthetic treatments of the maxillofacial complex. Hyaluronic acid fillers are predominantly used in aesthetic and functional procedures in the maxillofacial region. HA is a hydrogel of natural occurrence in human skin, belonging to the family of glycosaminoglycan’s (GAGs), present in abundance in the extracellular connective tissue matrix, It is a polymer used in the manufacture of artificial frameworks for tissue engineering due its nature biocompatible, biodegradable, non-immunogenic and non-thrombogenic, presenting benefits in the aesthetic and functional treatment of the skin and mucous membranes of the maxillofacial region. Nevertheless some complications are expected from its application to the living organism. These complications can be divided into early and late complications according to the patient’s symptoms. HA application liable to success shall respect important items/steps, thus its use must be correctly indicated and well applied by trained professionals who are familiar with facial anatomy, appropriate injection techniques and the preparation of the integumentary system. Early identification of complications and immediate intervention with medications and invasive procedures can significantly decrease the risk of long-term consequences. Key words: Facial implants, Dermic implants, Hyaluronic acid, Side effects, Maxillofacial complications.

THE EFFECT OF BICYCLOL ON THE STATE OF THE CONNECTIVE TISSUE COMPONENTS OF THE LIVER EXTRACELLULAR MATRIX IN THE COMPLEX THERAPY OF NON-ALCOHOLIC STEATOHEPATITIS WITH LIVER FIBROSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

The aim of the research was to determine the probable effect of metformin, rosuvastatin and bicyclol on markers of hepatocyte cytolysis in patients with nonalcoholic steatohepatitis and diabetes mellitus type 2 with diabetic kidney disease, the degree of hepatocyte steatosis and stage of liver fibrosis, as well as the content of extracellular protein and carbohydrate components in the blood tissues that are markers of the intensity of liver fibrosis and the progression of non-alcoholic steatohepatitis. Materials and methods. Studу of changes in the course of treatment of 60 patients with nonalcoholic steatohepatitis with type 2 diabetes mellitus and stage I–IV diabetic kidney disease was conducted, among whom 48 patients were diagnosed with mild non-alcoholic steatohepatitis and 12 – with moderate non-alcoholic steatohepatitis. A comorbid disease, i.e. type 2 diabetes mellitus of moderate severity, was registered in 100% of patients with nonalcoholic steatohepatitis: among them, 15 people had diabetes in the compensatory stage, 45 people – in the subcompensated stage. All patients with nonalcoholic steatohepatitis and type 2 diabetes had comorbid diabetic kidney disease, including 21 cases of stage I–II diabetic kidney disease, 20 cases of stage III diabetic kidney disease, and 19 patients with stage IV diabetic kidney disease. Results. Analysis of the results of extracellular matrix connective tissue metabolism in the blood of patients with non-alcoholic steatohepatitis on the background of type 2 diabetes mellitus and diabetic kidney disease indicated that the inflammatory and dysmetabolic process contributed to a significant imbalance of connective tissue components. In particular, activation of anabolic collagen was shown on the basis of an increase in blood protein-bound oxyproline by 2 times (p < 0.05), as well as a decrease in the intensity of collagen catabolism – based on a decrease in blood free oxyproline by 1.4 times (p < 0.05), which probably occurred due to inhibition of collagenolytic activity of blood plasma (by 1.4 times, p < 0.05). That is, activated processes of collagen synthesis were accompanied by inhibition of its degradation and accumulation in the extracellular matrix. We also found a significant increase in the blood content of hexosamines by 1.5 times (p < 0.05) and accelerated degradation of carbohydrate-protein components of the matrix (with an increase in the content of unbound fucose by 2.6 times, (p < 0.05)). Conclusions. The combination therapy with metformin, rosuvastatin in combination with Вicyclol in individuals with comorbid nonalcoholic steatohepatitis, type 2 diabetes mellitus and diabetic kidney disease for 3 months helped to eliminate the syndrome of cytolysis of hepatocytes, a significant reduction liver fibrosis intensity due to optimization of spectrum of connective tissue components of the extracellular matrix in the blood with a decrease in the content of markers of collagen anabolism, increase in the content of markers of collagen catabolism due to increased total collagenolytic activity of blood plasma, decrease in the content of hexosamines and carbohydrate protein markers.

Abstract 13435: Characterization of Open Chromatin in Human Mitral Valves to Identify Regulatory Mechanisms at Mitral Valve Prolapse Genetic Loci

Introduction: Mitral valve prolapse (MVP) is a common valve disease that leads to mitral insufficiency, heart failure, and sudden death. The identification of genetic risk loci provided insight into its genetic architecture, although the causal variants and target genes need to be fully characterized. Hypothesis: Functional genomic annotation, including chromatin accessibility profiles of human mitral valves, allows the characterization of variants and target genes at MVP loci. Methods: We determined open chromatin regions using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) from surgically removed human valves and primary cultures of fibroblasts. We analyzed the spatial conformation of MVP-associated loci using circular chromatin conformation capture (4C-Seq) with candidate causal variants as viewpoints. Candidate causal variants were followed-up using reporter assays and in silico analyses. Results: We mapped the open chromatin from 11 human mitral valves and 3 primary cell cultures. We found that mitral valve-specific ATAC-Seq peaks were enriched near genes involved in extracellular matrix organization, chondrocyte differentiation, and connective tissue development. We also found that MVP-associated variants (p<10 -5 ) observed in the MVP GWAS were significantly enriched (p<0.05) in mitral valve open chromatin regions, but not in heart tissue from ENCODE. We found that rs6723013 on Chr2 belongs to a valve-specific enhancer at the IGFBP5/TNS1 locus and is the most likely causal variant at this locus. We also identified several plausible causal SNPs and, by using 4C-Seq, potential target genes ( HIC1 and DPH1 ) at the SMG6/SRR locus. Conclusions: Here we describe unprecedented genome-wide open chromatin profiles from human mitral valves that indicate specific gene regulation profiles, compared to the heart. We also report in vitro functional evidence for potential causal variants and target genes at MVP risk loci involving established and new biological mechanisms relevant to mitral valve disease.

Long-Term Arterial Remodeling After Bioresorbable Scaffold Implantation 4-Year Follow-up of Quantitative Coronary Angiography, Histology and Optical Coherence Tomography.

Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated. After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively. There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT. At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.

Interstitial lung disease and diabetes.

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has been steadily increasing all over the world. DM and its associated micro and macrovascular complications result in significant morbidity and mortality. The microvascular complications are usually manifested as retinopathy, neuropathy, nephropathy and macrovascular complications generally affect the cardiovascular system. In addition to these complications, DM also affects the lungs because of its rich vascularity and abundance in connective tissue (collagen and elastin). DM has been found to cause microvascular complications and proliferation of extracellular connective tissue in the lungs, leading to decline in lung function in a restrictive pattern. Interstitial lung disease (ILD) includes a diverse group of disease conditions characterized by different degrees of inflammation and fibrosis in the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of the common type of idiopathic interstitial pneumonia with a high mortality rate. IPF is characterized by chronic progressive fibrosis leading to progressive respiratory failure. In this review we focus on lung as the target organ in DM and the association of DM and ILD with special emphasis on IPF.

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Inhibitory effect of natural metal ion chelators on the autolysis of sea cucumber (Stichopus japonicus) and its mechanism

Live sea cucumbers (Stichopus japonicus) were stored in a solution containing oxalic acid and tea polyphenols as natural metal ion chelators. The inhibitory effects of these chelators on the autolysis phenomenon and the underlying mechanism of action were investigated for the first time by using scanning electron microscopy, differential scanning calorimetry, low-field nuclear magnetic resonance and confocal laser scanning microscopy. External stimuli cause autolysis through the release of calcium ions (Ca2+) from cells into the extracellular connective tissue, initiating activity of the matrix metalloprotease (MMP) in the sea cucumber body wall (SCBW). MMP subsequently degrades the microfibrillar networks, that support the interconnecting collagen fibres and the interfibrillar proteoglycan bridges linking the collagen fibrils, to release the water restricted within the interspaces between collagen fibres and collagen fibrils, ultimately causing mucoid degeneration of SCBW. The natural metal ion chelators significantly inhibited the activation of MMP by chelating Ca2+, consequently effectively preventing the autolysis of SCBW.

LCAT, ApoD, and ApoA1 Expression and Review of Cholesterol Deposition in the Cornea.

Lecithin:cholesterol acyltransferase (LCAT) is an enzyme secreted by the liver and circulates with high-density lipoprotein (HDL) in the blood. The enzyme esterifies plasma cholesterol and increases the capacity of HDL to carry and potentially remove cholesterol from tissues. Cholesterol accumulates within the extracellular connective tissue matrix of the cornea stroma in individuals with genetic deficiency of LCAT. LCAT can be activated by apolipoproteins (Apo) including ApoD and ApoA1. ApoA1 also mediates cellular synthesis of HDL. This study examined the expression of LCAT by epithelial cells, keratocytes, and endothelial cells, the cell types that comprise from anterior to posterior the three layers of the cornea. LCAT and ApoD were immunolocalized to all three cell types within the cornea, while ApoA1 was immunolocalized to keratocytes and endothelium but not epithelium. In situ hybridization was used to detect LCAT, ApoD, and ApoA1 mRNA to learn what cell types within the cornea synthesize these proteins. No corneal cells showed mRNA for ApoA1. Keratocytes and endothelium both showed ApoD mRNA, but epithelium did not. Epithelium and endothelium both showed LCAT mRNA, but despite the presence of LCAT protein in keratocytes, keratocytes did not show LCAT mRNA. RNA sequencing analysis of serum-cultured dedifferentiated keratocytes (commonly referred to as corneal stromal fibroblasts) revealed the presence of both LCAT and ApoD (but not ApoA1) mRNA, which was accompanied by their respective proteins detected by immunolabeling of the cultured keratocytes and Western blot analysis of keratocyte lysates. The results indicate that keratocytes in vivo show both ApoA1 and LCAT proteins, but do not synthesize these proteins. Rather, keratocytes in vivo must take up ApoA1 and LCAT from the corneal interstitial tissue fluid.

The mechanisms and potential of stem cell therapy for penile fibrosis.

Fibrosis is often caused by chronic tissue injury leading to a persisting inflammatory response with excessive accumulation of extracellular connective tissue proteins. Peyronie's disease, urethral stricture and penile (corpora cavernosa) fibrosis are localized fibrotic disorders of the penile connective tissues that can substantially impair a patient's quality of life. Research over the past few decades has revealed the ability of stem cells to secrete a wide range of paracrine factors, a characteristic that could be exploited therapeutically to prevent and treat several inflammatory and fibrotic diseases. In preclinical studies, mesenchymal stem cells (MSCs) have proven to be the most effective and readily available type of stem cells for therapeutic use. An important advantage of MSCs is their ability to circumvent the immune system and function as immunomodulatory 'drug stores' to influence multiple cell types simultaneously. Many studies using stem cells have been applied exclusively to corpora cavernosa fibrosis owing to its well-established disease models. A plethora of preclinical data suggest the benefit of stem cells for use in penile fibrosis. However, their exact mechanism of action and optimal timing and mode of administration must be determined before clinical translation.

Laporan Kasus: Pembesaran gingiva yang diinduksi fenitoin

Gingival enlargement is a kind of oral manifestation, that can caused by induction of anticonvulsant drugs. Phenytoin is one of anticonvulsant drug that can caused gingival enlargement. Gingival enlargement in this case developed until grade III. The patient was highly phenytoin dependent and can’t be reconciled. The aim of this paper is to find out the cause of phenytoin induced gingival enlargement and its treatment. A 20 years old woman came to RSGM UNSOED to check her swollen gums. The patient’s history was epilepsy and had been regularly taking phenytoin. The patient was taking 30 mg phenobarbital, 10 mg clobazam, 1 mg folic acid and 100 mg phenytoin 2 times a day with 2 capsules each time that had been consumted for 4 years. Phenytoin as anticonvulsant drug has side effects that can caused gingival enlargement, this is because phenytoin can increase extracellular connective tissue, collagen and fibrous.

Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation.

Transglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as coeliac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases, the epitope spreading is remarkable, while in some inherited pathologies, a unique compensation of the lost enzyme function is noted.

PCM and TAT co-modified liposome with improved myocardium delivery: in vitro and in vivo evaluations

In this study, PCM and TAT co-modified liposome was developed as a novel drug carrier for myocardium delivery with evaluation of its in vitro and in vivo properties. Liposomes containing fluorescent probe coumarin-6 were prepared by thin-film hydration. The PCM ligands specifically bind to the PCM receptors in the extracellular connective tissue of primary myocardium cells (MCs), while the TAT ligands functioned as a classical cell penetrating peptide to make liposomes internalized by MCs. The unmodified liposome (L), PCM-modified liposome (PL), TAT-modified liposome (TL) and PCM and TAT co-modified liposome (PTL) were prepared and characterized. The cellular uptake and intracellular distribution of various liposomes by MCs demonstrated that PTL had the best delivery capability. Peptide inhibition assay indicated that the uptake of PL could be inhibited by PCM. However, TAT could almost not suppress the uptake of TL. In addition, the CCK-8 experiments showed that liposomes had low cytotoxicity. In vivo fluorescent images of frozen sections and HPLC-fluorescence analysis further demonstrated that PTL had highest myocardium distribution. The results of this study demonstrated that PCM and TAT co-modifying could improve the myocardial targeting ability of liposome.

The Inelastic Hierarchy: Multiscale Biomechanics of Weak Bonds

Living tissue is a mechanical chameleon. It may behave as a viscous or elastic material, depending on how fast and strong you pull on it. It also responds plastically to permanent loads, as evidenced by the Tutankhamun-style lobe-stretching ear piercings that are currently regaining popularity. To mechanistically explain and quantitatively predict how such impressive versatility and resilience is accomplished by the molecular composition and architecture of living matter is the holy grail of biomechanics.

Early wound healing of laser in situ keratomileusis–like flaps after treatment with human corneal stromal stem cells

PurposeTo use a well-established organ culture model to investigate the effects of corneal stromal stem cells on the optical and biomechanical properties of corneal wounds after laser in situ keratomileusis (LASIK)–like flap creation.SettingSchool of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom.DesignExperimental study.MethodsThe LASIK-like flaps were produced in sheep corneas. The flap beds were treated with corneal stromal stem cells and were then replaced and allowed to heal for different periods of up to 3 weeks in organ culture. The optical transmission of the cornea, the force required to detach the flap, and the presence of myofibroblasts near the flap bed were measured.ResultsCorneal stromal stem cell–treated flap beds were statistically significantly more transparent after 3 weeks in culture than the untreated controls. At 3 weeks, the mean force necessary to detach the flap was more than twice the force required for the respective control samples. Concurrently, there were 44% activated cells immediately below the flap margin of the controls compared with 29% in the same region of the corneal stromal stem cell–treated flaps.ConclusionsIn this system, the presence of corneal stromal stem cells at the wound margin significantly increased the adherence of LASIK-like flaps while maintaining corneal transparency. It is postulated that this is achieved by the deposition of extracellular connective tissue similar to that found in the normal cornea and by the paucity of activated keratocytes (myofibroblasts), which are known to scatter a significant amount of the incident light.Financial DisclosureNo author has a financial or proprietary interest in any material or method mentioned.