scholarly journals The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

2021 ◽  
Author(s):  
Bonnie C. Carney ◽  
Jeffrey W. Shupp ◽  
Taryn E. Travis

Hypertrophic scar (HTS) is a fibrotic skin disorder that is marked by excessive inflammation and extracellular matrix deposition in response to cutaneous traumatic injuries such as burns, lacerations, incisions, and abrasions. HTS has various risk factors, available treatments, and treatment effectiveness. Research at the basic, translational, and clinical levels are in their infancy compared to fibrotic diseases in other organ systems. This chapter will review current in vitro and in vivo modeling, and highlight research needs to address gaps in the study of HTS. The following topics will be discussed in the chapter: a. Basic Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research b. Translational Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research c. Clinical Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research.

2021 ◽  
Vol 8 ◽  
Author(s):  
Francesco Cinetto ◽  
Jessica Ceccato ◽  
Ilaria Caputo ◽  
Daniela Cangiano ◽  
Barbara Montini ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix deposition, consequent to epithelial lung injury and myofibroblast activation, and inflammatory response. Glycogen synthase kinase 3 (GSK-3) is a serine–threonine kinase involved in several pathways, and its inhibition has been already suggested as a therapeutic strategy for IPF patients. There is evidence that GSK-3 is able to induce matrix metalloproteinase (MMP) expression and that its inhibition modulates MMP expression in the tissues. The aim of our study was to investigate the role of GSK-3 and its inhibition in the modulation of MMP-9 and -2 in an in vivo mouse model of lung fibrosis and in vitro using different cell lines exposed to pro-inflammatory or pro-fibrotic stimuli. We found that GSK-3 inhibition down-modulates gene expression and protein levels of MMP-9, MMP-2, and their inhibitors TIMP-1 and TIMP-2 in inflammatory cells harvested from bronchoalveolar lavage fluid (BALF) of mice treated with bleomycin as well as in interstitial alveolar macrophages and cuboidalized epithelial alveolar cells. To the same extent, GSK-3 inhibition blunted the increased MMP-9 and MMP-2 activity induced by pro-fibrotic stimuli in a human lung fibroblast cell line. Moreover, the αSMA protein level, a marker of fibroblast-to-myofibroblast transition involved in fibrosis, was decreased in primary fibroblasts treated with TGFβ following GSK-3 inhibition. Our results confirm the implication of GSK-3 in lung inflammation and fibrosis, suggesting that it might play its role by modulating MMP expression and activity but also pushing fibroblasts toward a myofibroblast phenotype and therefore enhancing extracellular matrix deposition. Thus, its inhibition could represent a possible therapeutic strategy.


Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 969
Author(s):  
Xingyi Jiang ◽  
Qinchun Rao

Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.


Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Nilufar Z. Mamadalieva ◽  
Davlat Kh. Akramov ◽  
Ludger A. Wessjohann ◽  
Hidayat Hussain ◽  
Chunlin Long ◽  
...  

The genus Lagochilus (Lamiaceae) is native to Central, South-Central, and Eastern Asia. It comprises 44 species, which have been commonly used as herbal medicines for the treatments of various ailments for thousands of years, especially in Asian countries. This review aims to summarize the chemical constituents and pharmacological activities of species from the genus Lagochilus to unveil opportunities for future research. In addition, we provide some information about their traditional uses, botany, and diversity. More than 150 secondary metabolites have been reported from Lagochilus, including diterpenes, flavonoids, phenolic compounds, triterpenoids, iridoid glycosides, lignans, steroids, alkaloids, polysaccharides, volatile, non-volatile and aromatic compounds, lipids, carbohydrates, minerals, vitamins, and other secondary metabolites. In vitro and in vivo pharmacological studies on the crude extracts, fractions, and isolated compounds from Lagochilus species showed hemostatic, antibacterial, anti-inflammatory, anti-allergic, cytotoxic, enzyme inhibitory, antispasmodic, hypotensive, sedative, psychoactive, and other activities.


2014 ◽  
Vol 2014 ◽  
pp. 1-32 ◽  
Author(s):  
Shamkant B. Badgujar ◽  
Vainav V. Patel ◽  
Atmaram H. Bandivdekar

Foeniculum vulgareMill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology ofFoeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates thatFoeniculum vulgareremains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in severalin vitroandin vivopharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property.Foeniculum vulgarehas emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Patrizia Camelliti ◽  
Gil Bub ◽  
Daniel J Stuckey ◽  
Christian Bollensdorff ◽  
Damian J Tyler ◽  
...  

Sarcomere length (SL) is a fundamental parameter underlying the Frank Starling relation in the heart, as it offers an absolute representation of myocardial stretch. Previous studies addressed the Frank Starling relation by measuring SL in isolated myocytes or muscle strips. Here, we report first data obtained using a novel technique to measure sub-epicardial SL in perfused hearts. Rat hearts were Langendorff perfused (normal Tyrode solution) at a constant pressure of 90mmHg, labeled with the fluorescent membrane marker di-4-ANEPPS, and then arrested with high-K + Tyrode for either 2-photon microscopy (n=4) or MRI (n=4). Image analysis software was developed to extract SL at the cell level from >1,400 2-photon images (Fig 1 ) and correct for cell angle. SL increased by 10±2 % between 30 and 80 min of perfusion (1.98±0.04 to 2.17±0.03 μm; p<0.05; Fig 1 ). Measurements of left ventricular myocardial volume (LVMV) were made in vivo and in perfused hearts using 3D MRI. LVMV increased by 24±7% from in vivo to 30 min of perfusion, and by 11±3 % between 30 and 90 min (539±35; 664±44; 737±49 mm 3 , respectively; p<0.05; Fig 1 ). We show that SL can be measured in isolated perfused hearts. The method allowed monitoring of changes in SL over time, and showed that SL and LVMV increase to a similar extent during 30–80 min perfusion with crystalloid solution, probably due to tissue oedema. This result, together with the increase in LVMV during the first 30 min, highlights the pronounced differences between in vivo , in situ , and in vitro model systems for studies of cardiac physiology and mechanics. Future research will compare changes in SL in healthy hearts and disease models involving contractile dysfunction. Figure 1: Left: 2-photon microscopy image of di-4-ANEPPS labeled myocardium. Right: SL and LVMV changes over time.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0053
Author(s):  
Jianying Zhang ◽  
Daibang Nie ◽  
Guangyi Zhao ◽  
Susheng Tan ◽  
MaCalus Hogan ◽  
...  

Category: Hindfoot Introduction/Purpose: Entheses have a special fibrocartilage transition zone where tendons and ligaments attach to bone. Enthesis injury is very common, and the reattachment of tendon to bone is a great challenge because healing takes place between a soft tissue (tendon) and a hard tissue (bone). We have now developed a kartogene (KGN)-containing polymer scaffold (KGN-P) that can precisely deliver KGN to damaged enthesis area. The effects of the KGN-containing polymer on the healing of wounded TBJ were investigated in vitro and in vivo. Methods: The proliferation and chondrogenesis of rat Achilles tendon stem cells (TSCs) grown in four conditions were measured: normal medium (Control); normal medium with 100 nM KGN (KGN); lysine diisocyanate (LDI)-glycerol scaffold with normal medium (LDI-P); LDI-glycerol-KGN scaffold with normal medium (KGN-P).A wound (1 mm) was created on each hind leg Achilles enthesis of all 8 rats (3 months old). The wounds were then treated either with 10 ul saline (Wound); or 10 ul of 10 uM KGN (KGN); or LDI polymer scaffold (LDI-P); or KGN-containing polymer scaffold (KGN-P). The rats were sacrificed on day 15 and 30 post-surgery, and their Achilles entheses were collected for gross inspection and histochemical analysis. Results: KGN-containing polymers have sponge-like structures (Fig. 1A-D), and release KGN in a time- and temperature-dependent manner (Fig. 1E). KGN-P scaffold induced chondrogenesis of TSCs (Fig. 2D, 2H) without changing cell proliferation (Fig. 2I), and enhanced fibrocartilage-like tissue formation (Fig. 3E). KGN (Fig. 3C) and LDI-P (Fig. 3D) treated groups exhibited unhealed wound areas as in saline group (Fig. 3B). Finally, KGN-P and KGN treated rat TSCs underwent chondrogenesis by upregulating collagen II, aggrecan, and SOX-9 expression (Fig. 3F). Conclusion: Our results showed that KGN-containing polymer scaffold enhanced wounded enthesis healing by inducing TSC chondrogenesis and promoting the formation of the fibrocartilage in the wound site. The KGN-P may be used for regeneration of wounded entheses in clinical settings. Future research will focus on optimizing KGN concentration and releasing rate in the polymer scaffold during enthesis healing.


2021 ◽  
Vol 42 ◽  
pp. e67649
Author(s):  
Marta Sánchez ◽  
Elena González-Burgos ◽  
Irene Iglesias ◽  
M. Pilar Gómez-Serranillos Cuadrado

Valeriana officinalis L. (Caprifoliaceae family) has been traditionally used to treat mild nervous tension and sleep problems. The basis of these activities are mainly attributed to valerenic acid through the modulation of the GABA receptor. Moreover, V. officinalis is claimed to have other biological activities such as cardiovascular benefits, anticancer, antimicrobial and spasmolytic.  The current review aims to update the biological and pharmacological studies (in vitro, in vivo and clinical trials) of V. officinalis and its major secondary metabolites in order to guide future research. Databases PubMed, Science Direct and Scopus were used for literature search including original papers written in English and published between 2014 and 2020. There have been identified 33 articles which met inclusion criteria. Most of these works were performed with V. officinalis extracts and only a few papers (in vitro and in vivo studies) evaluated the activity of isolated compounds (valerenic acid and volvalerenal acid K). In vitro studies focused on studying antioxidant and neuroprotective activity. In vivo studies and clinical trials mainly investigated activities on the nervous system (anticonvulsant activity, antidepressant, cognitive problems, anxiety and sleep disorders). Just few studies were focused on other different activities, highlight effects on symptoms of premenstrual and postmenopausal syndromes. Valeriana officinalis continues to be one of the medicinal plants most used by today's society for its therapeutic properties and whose biological and pharmacological activities continue to arouse great scientific interest as evidenced in recent publications. This review shows scientific evidence on traditional uses of V. officinalis on nervous system.


2020 ◽  
Author(s):  
Amparo López-Carrasco ◽  
Susana Martín-Vañó ◽  
Rebeca Burgos-Panadero ◽  
Ezequiel Monferrer ◽  
Ana P Berbegall ◽  
...  

Abstract Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We have applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN amplified SK-N-BE(2) and the ALK mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of both cell lines are affected. Results We describe a remarkable subclonal selection of some genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. Specially, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. Genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.


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