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Angiogenesis is vital to developmental, regenerative and repair processes. It is normally regulated by a balanced production of pro- and anti-angiogenic factors. Alterations in this balance under pathological conditions are generally mediated through up-regulation of pro-angiogenic and/or downregulation of anti-angiogenic factors, leading to growth of new and abnormal blood vessels. The pathological manifestation of many diseases including cancer, ocular and vascular diseases are dependent on the growth of these new and abnormal blood vessels. Thrompospondin-1 (TSP1) was the first endogenous angiogenesis inhibitor identified and its anti-angiogenic and anti-inflammatory activities have been the subject of many studies. Studies examining the role TSP1 plays in pathogenesis of various ocular diseases and vascular dysfunctions are limited. Here we will discuss the recent studies focused on delineating the role TSP1 plays in ocular vascular development and homeostasis, and pathophysiology of various ocular and vascular diseases with a significant clinical relevance to human health. [ABSTRACT FROM AUTHOR]

Extra cellular matrix (ECM) incorporated calcium hydroxyapatite bound with triphasic silica is a custom made bone graft with hybrid properties which is used for bone regeneration. A promising new technique for preparing natural matrices for bone regeneration now in trend is decellularisation. According to reports, the ECM activates mesenchymal stem cells, speeding up bone healing. Although research employing hard tissues like bone are scarce, successful decellularisation has been done using a variety of tissues including skin, cartilage and tendon. The study was carried out in rat calvaria; critical size defects were created and later grafted with decellularised tissue engineered HASi bioceramic (test) and plain HASi bioceramic (control) on left and right side respectively. Radiography was used to assess changes in the graft, the rate of its degradation and the degree of bone repair. Postoperative dorsoventral view of the skull was taken immediately after surgery and thereafter on 2nd, 4th, 8th and 12th week post-surgery. The grafts were found to remain stable throughout the healing period. By 4th week onwards signs of gradual degradation of material with regeneration of bone could be noticed especially on test side compared to control. Test material was found to be completely integrated with host bone by eight weeks whereas control graft took 12 weeks. At twelve weeks, both the test and control grafts showed complete integration with host bone. It was concluded that the test graft material successfully hastened bone regeneration, making it a promising alternative to conventional bone grafts.

Abstract In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96–384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations. Graphical Abstract

In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96–384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations. [ABSTRACT FROM AUTHOR]

Prolonged exposure to fine dust (FD) increases the risk of skin inflammation. Stimulated epidermal cells release growth factors into their extracellular environment, which can induce inflammation in dermal cells. Algae are considered rich sources of bioactive materials. The present study emphasized the effect of low-molecular-weight fucoidan isolated from Sargassum confusum (LMF) against FD-induced inflammation in HaCaT keratinocytes and underneath fibroblasts (HDFs) in an integrated culture model. HDFs were treated with media from FD-stimulated HaCaT with LMF treatments (preconditioned media). The results suggested that FD increased the oxidative stress in HaCaT, thereby increasing the sub-G1 phase of the cell cycle up to 587%, as revealed via flow cytometric analysis. With preconditioned media, HDFs also displayed oxidative stress; however, the increase in the sub-G1 phase was insignificant compared with HaCaT. LMF dose-dependently regulated the NF-κB/MAPK signaling in HaCaT. Furthermore, significant downregulation in NF-κB/MAPK signaling, as well as inflammatory cytokines, tissue inhibitors of metalloproteinases, matrix metalloproteinases, and reduction in relative elastase and collagenase activities related to the extracellular matrix degeneration were observed in HDFs with a preconditioned media treatment. Therefore, we concluded that HDFs were protected from inflammation by preconditioned media. Continued research on tissue culture and in vivo studies may reveal the therapeutic potential of LMF. [ABSTRACT FROM AUTHOR]

Abstract Background Evolution in the in vitro cell culture from conventional 2D to 3D technique has been a significant accomplishment. The 3D culture models have provided a close and better insight into the physiological study of the human body. The increasing demand for organs like liver, kidney, and pancreas for transplantation, rapid anti-cancer drug screening, and the limitations associated with the use of animal models have attracted the interest of researchers to explore 3D organ culture. Main body Natural, synthetic, and hybrid material-based hydrogels are being used as scaffolds in 3D culture and provide 'close-to-in vivo’ structures. Organoids: the stem cell-derived small size 3D culture systems are now favored due to their ability to mimic the in-vivo conditions of organ or tissue and this characteristic has made it eligible for a variety of clinical applications, drug discovery and regenerative medicine are a few of the many areas of application. The use of animal models for clinical applications has been a long-time ethical and biological challenge to get accurate outcomes. 3D bioprinting has resolved the issue of vascularization in organoid culture to a great extent by its layer-by-layer construction approach. The 3D bioprinted organoids have a popular application in personalized disease modeling and rapid drug development and therapeutics. Short conclusions This review paper, focuses on discussing the novel organoid culture approach, its advantages and limitations, and potential applications in a variety of life science areas namely cancer research, cell therapy, tissue engineering, and personalized medicine and drug discovery. Graphical Abstract

Background & Objective: Gastric cancer (GC) is considered one of the main reasons for cancer-related mortalities among Iranians. Kindlin-1 is an adhesion protein member of integrin-interacting proteins, regulating integrin activation through direct interaction with β-integrin. Therefore, kindlin-1 can be involved in the regulation of cell proliferation and adhesion. In the present study, we assessed the possible role of kindlin-1 in GC progression and metastasis.Methods: KINDLIN1 messenger RNA (mRNA) expression was assessed in tumor tissues from 80 GC patients in comparison with normal tissues using real-time polymerase chain reaction (PCR).Results: The levels of KINDLIN1 expressions were significantly correlated with sex (P=0.05) and tumor location (P=0.002). KINDLIN1 expression was also significantly associated with lymph node metastasis among the helicobacter pylori (HP)-negative cases (P=0.001). Moreover, a significant association between age and KINDLIN1 expression was observed among the HP-positive cases (P=0.039).Conclusion: In the present study, we introduced KINDLIN1 as a location-specific marker for cardia gastric carcinoma. Moreover, it was observed that KINDLIN1 could be used as a sex-dependent diagnostic marker of GC patients.

Objectives Evidence shows that dysfunctional SSc keratinocytes contribute to fibrosis by altering dermal homeostasis. Whether IL-25, an IL-17 family member regulating many epidermal functions, takes part in skin fibrosis is unknown. Here we address the role of IL-25 in skin fibrosis. Methods The expression of IL-25 was evaluated by immunofluorescence and in situ hybridization in 10 SSc and seven healthy donor (HD) skin biopsies. Epidermal equivalents (EE) reconstituted by primary HD keratinocytes were used as a model to study transcriptomic changes induced by IL-25 in the epidermis. RNA expression profile in EEs was characterized by RNAseq. The conditioned medium (CM) from primary SSc and HD keratinocytes primed with IL-25 was used to stimulate fibroblasts. IL-6, IL-8, MMP-1, type-I collagen (Col-I), and fibronectin production by fibroblasts was assessed by ELISA. Results SSc epidermis expressed lower levels of IL-25 compared with HDs. In EEs, IL-25 regulated several molecular pathways related to wound healing and extracellular matrix remodelling. Compared with control CM, the CM from IL-25-primed keratinocytes enhanced the fibroblast production of MMP-1, IL-6 and IL-8, but not of Col-I nor fibronectin. However, IL-25 significantly reduced the production of Col-I when applied directly to fibroblasts. The activation of keratinocytes by IL-25 was receptor-dependent and evident after a very short incubation time (10 min), largely mediated by IL-1, suggesting enhanced and specific release of preformed mediators. Conclusions These results show that IL-25 participates in skin homeostasis, and its decreased expression in SSc may contribute to skin fibrosis by favouring extracellular matrix deposition over degradation. [ABSTRACT FROM AUTHOR]

Collagens are the most abundant proteins in the extra cellular matrix/ECM of human tissues that are encoded by different genes. There are single nucleotide polymorphisms/SNPs which are considered as the most useful biomarkers for some disease diagnosis or prognosis. The aim of this study is screening and identifying the functional missense SNPs of human ECM-collagens and investigating their correlation with human abnormalities. All of the missense SNPs were retrieved from the NCBI SNP database and screened for a global frequency of more than 0.1. Seventy missense SNPs that met the screening criteria were characterized for functional and stability impact using six and three protein analysis tools, respectively. Next, HOPE and geneMANIA analysis tools were used to show the effect of SNPs on three-dimensional structure (3D) and physical interaction of proteins. Results showed that 13 missense SNPs (rs2070739, rs28381984, rs13424243, rs1800517, rs73868680, rs12488457, rs1353613, rs59021909, rs9830253, rs2228547, rs3753841, rs2855430, and rs970547), which are in nine different collagen genes, affect the structure and function of different collagen proteins. Among these polymorphisms, COL4A3-rs13424243 and COL6A6-rs59021909 were predicted as the most effective ones. On the other hand, designed mutated and native 3D of rs13424243 variant illustrated that it can disturb the protein motifs. Also, geneMANIA predicted that COL4A3 and COL6A6 are interacting with some proteins including: DDR1, COL6A1, COL11A2 and so on. Based on our findings, ECM-collagens functional SNPs are important and may be considered as a risk factor or molecular marker for human disorders in the future studies. [ABSTRACT FROM AUTHOR]

The evaluation of nanomechanical properties of tissues in health and disease is of increasing interest to scientists. It has been confirmed that these properties, determined in part by the composition of the extracellular matrix, significantly affect tissue physiology and the biological behavior of cells, mainly in terms of their adhesion, mobility, or ability to mutate. Importantly, pathophysiological changes that determine disease development within the tissue usually result in significant changes in tissue mechanics that might potentially affect the drug efficacy, which is important from the perspective of development of new therapeutics, since most of the currently used in vitro experimental models for drug testing do not account for these properties. Here, we provide a summary of the current understanding of how the mechanical properties of brain tissue change in pathological conditions, and how the activity of the therapeutic agents is linked to this mechanical state. [ABSTRACT FROM AUTHOR]

Background and aim: Although, the anticancer potential of Aqueous Azadirachta indica leaf extract (AAILE) has been robustly established against cutaneous squamous cell carcinoma (SCC) in mice, however, its ability in modulating tumor associated extra cellular matrix (ECM) is largely unknown. Therefore, the present study was conceived to explore changes in ECM during murine skin cancer and its chemoprevention by AAILE. Experimental procedure: Skin tumors were induced using a two-stage model of carcinogenesis employing topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as carcinogen and promoter respectively. AAILE was administered orally to the animals. Male Laca mice were divided into four groups: control, AAILE, DMBA/TPA and AAILE + DMBA/TPA. Results: The tumors obtained in DMBA/TPA and AAILE + DMBA/TPA groups were histologically identified as SCC. Tumor induction in these groups was accompanied by raised serum carcinoembryonic antigen (CEA) levels when compared to control counterparts. Assessment of hydroxyproline levels and histochemical staining with sirius red and trichrome stain revealed an increase in collagen in tumors of DMBA/TPA group. An increase in glycosaminoglycans (GAGs) levels was also observed in DMBA/TPA group as made evident by biochemical studies and histochemical staining using mucicarmine and alcian blue-periodic acid schiff’s stain. Administration of AAILE to DMBA/TPA treated animals caused a decrease in collagen and GAG levels along with a decrease in serum CEA levels. Conclusion: Skin tumors exhibited altered presence of ECM components which is indicative of a modified ECM. AAILE administration antagonised tumor associated ECM alterations which may be contributing to its chemopreventive activity as reported previously.

[Display omitted] • In cultured meat (CM) production, Scaffolding plays an important role by aiding cell adhesion, growth, differentiation, and alignment. A wide array of research efforts is ongoing in scaffolding technologies for achieving the real meat structure on the principality of biomedical research and to replace serum free CM production. Scaffolds made of animal-derived biomaterials are found efficient in replicating the extracellular matrix (ECM), thus focus should be paid to utilize animal byproducts for this purpose. Plant-derived scaffolding biomaterial could be promising options to reduce cost of CM production. Furthermore, techniques like electrospinning, modified electrospinning, 3D bioprinting should be focused on to create 3D porous scaffolds to mimic the ECM of the muscle tissue. This review discusses recent advances in cutting edge scaffolding techniques and edible biomaterials related to structured CM production. • Animal derived biomaterials are showing promise for efficient scalable scaffold production and would be sustainable, inexpensive, nontoxic, edible, degradable, and easily available. • Cutting edge techniques like electrospinning, modified spinning and 3D bioprinting could be promising for the creation of elongated 3D scaffolds for directional cell growth and structured end product production. • Extended focus needs on using biodegradable, ecofriendly biomaterials and solvents for safer green electrospinning. In cultured meat (CM) production, Scaffolding plays an important role by aiding cell adhesion, growth, differentiation, and alignment. The existence of fibrous microstructure in connective and muscle tissues has attracted considerable interest in the realm of tissue engineering and triggered the interest of researchers to implement scaffolding techniques. A wide array of research efforts is ongoing in scaffolding technologies for achieving the real meat structure on the principality of biomedical research and to replace serum free CM production. Scaffolds made of animal-derived biomaterials are found efficient in replicating the extracellular matrix (ECM), thus focus should be paid to utilize animal byproducts for this purpose. Proper identification and utilization of plant-derived scaffolding biomaterial could be helpful to add diversified options in addition to animal derived sources and reduce in cost of CM production through scaffolds. Furthermore, techniques like electrospinning, modified electrospinning and 3D bioprinting should be focused on to create 3D porous scaffolds to mimic the ECM of the muscle tissue and form real meat-like structures. This review discusses recent advances in cutting edge scaffolding techniques and edible biomaterials related to structured CM production. [ABSTRACT FROM AUTHOR]

Skeletal muscle and adipose tissue are characterized by unique structural features finely tuned to meet specific functional demands. In this study, we investigated the passive mechanical properties of soleus (SOL), extensor digitorum longus (EDL) and diaphragm (DIA) muscles, as well as subcutaneous (SAT), visceral (VAT) and brown (BAT) adipose tissues from 13 C57BL/6J mice. Thereto, alongside stress-relaxation assessments we subjected isolated muscles and adipose tissues (ATs) to force-extension tests up to 10% and 30% of their optimal length, respectively. Peak passive stress was highest in the DIA, followed by the SOL and lowest in the EDL (p < 0.05). SOL displayed also the highest Young's modulus and hysteresis among muscles (p < 0.05). BAT demonstrated highest peak passive stress and Young's modulus followed by VAT (p < 0.05), while SAT showed the highest hysteresis (p < 0.05). When comparing data across all six biological specimens at fixed passive force intervals (i.e., 20–40 and 50–70 mN), skeletal muscles exhibited significantly higher peak stresses and strains than ATs (p < 0.05). Young's modulus was higher in skeletal muscles than in ATs (p < 0.05). Muscle specimens exhibited slower force relaxation in the first phase compared to ATs (p < 0.05), while there was no significant difference in behavior between muscles and AT in the second phase of relaxation. The study revealed distinctive mechanical behaviors specific to different tissues, and even between different muscles and ATs. These variations in mechanical properties are likely such to optimize the specific functions performed by each biological tissue. Structural differences among different muscles and adipose depots are optimized for their unique functions. SOL: soleus muscle, EDL: extensor digitorum longus muscle, DIA: diaphragm muscle; SAT: subcutaneous adipose tissue, VAT: visceral adipose tissue, BAT, brown adipose tissue. [Display omitted] [ABSTRACT FROM AUTHOR]

The enteric nervous system (ENS) regulates gastrointestinal motility, secretion, and absorption. Developmental ENS dysplasia causes intestinal ganglion dysfunction, including Hirschsprung's disease. Given their potential ability to replenish insufficient neurons, transplantation of enteric neural cells provides the prospect of a cure. In this study, we used an ex vivo mouse colon transplant model to demonstrate that treatment with collagenase and fibronectin altered the migration of transplanted cells from the direction of the colon surface toward the lumen. Collagenase-treated colons exhibited enhanced expression of type III and VI collagens, which inhibited fibronectin-induced enteric neural crest cell (ENCC) migration. Invasion of neurospheres into colon was dependent on preoperative treatment of recipient colon with collagenase and fibronectin, which enhanced neurosphere motility towards the direction of colon lumen. Infiltration of transplanted ENCCs into the colon increased proportionally to the degree of dedifferentiation of surrounding smooth muscle cells, which was induced in a neurosphere-dependent manner in collagenase-treated colon. Furthermore, induction of GDNF expression, a Ret ligand that promotes enteric neural cell migration, was observed in treated colons. Our results suggest that the environment provided by the extracellular matrix of the colon surface affects the direction of transplanted ENCC migration. Moreover, these findings demonstrating that ENCCs can be accepted by the recipient colon will help to refine current strategies for cell therapy. • Transplanted enteric neural crest cells (ENCCs) migrate toward the colon surface. • Transplanted ENCCs invaded the lumen in collagenase-fibronectin-treated colon. • Collagenase-fibronectin decreased colonic SMA expression in ENCC-dependent manner. • Collagenase-fibronectin enhanced colonic GDNF expression in ENCC-dependent manner. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric cancer (GC) is one of the most common cancers in the world with a high ratio of mortality. Regarding the late diagnosis, there is a high ratio of distant metastasis among GC cases. Despite the recent progresses in therapeutic modalities, there is not still an efficient therapeutic method to increase survival rate of metastatic GC cases. Main body Apart from the various intracellular signaling pathways which are involved in tumor cell migration and metastasis, the local microenvironment is also a critical regulator of tumor cell migration. Indeed, the intracellular signaling pathways also exert their final metastatic roles through regulation of extra cellular matrix (ECM). Therefore, it is required to assess the role of extra cellular components in biology of GC. Conclusion In the present review, we summarize 48 of the significant ECM components including 17 ECM modifying enzymes, seven extracellular angiogenic factors, 13 cell adhesion and cytoskeletal organizers, seven matricellular proteins and growth factors, and four proteoglycans and extra cellular glycoproteins. This review paves the way of determination of a specific extra cellular diagnostic and prognostic panel marker for the GC patients.

Prolonged exposure to fine dust (FD) increases the risk of skin inflammation. Stimulated epidermal cells release growth factors into their extracellular environment, which can induce inflammation in dermal cells. Algae are considered rich sources of bioactive materials. The present study emphasized the effect of low-molecular-weight fucoidan isolated from Sargassum confusum (LMF) against FD-induced inflammation in HaCaT keratinocytes and underneath fibroblasts (HDFs) in an integrated culture model. HDFs were treated with media from FD-stimulated HaCaT with LMF treatments (preconditioned media). The results suggested that FD increased the oxidative stress in HaCaT, thereby increasing the sub-G1 phase of the cell cycle up to 587%, as revealed via flow cytometric analysis. With preconditioned media, HDFs also displayed oxidative stress; however, the increase in the sub-G1 phase was insignificant compared with HaCaT. LMF dose-dependently regulated the NF-κB/MAPK signaling in HaCaT. Furthermore, significant downregulation in NF-κB/MAPK signaling, as well as inflammatory cytokines, tissue inhibitors of metalloproteinases, matrix metalloproteinases, and reduction in relative elastase and collagenase activities related to the extracellular matrix degeneration were observed in HDFs with a preconditioned media treatment. Therefore, we concluded that HDFs were protected from inflammation by preconditioned media. Continued research on tissue culture and in vivo studies may reveal the therapeutic potential of LMF.

During development, biomechanical forces contour the body and provide shape to internal organs. Using genetic and molecular approaches in combination with a FRET-based tension sensor, we characterized a pulling force exerted by the elongating pharynx (foregut) on the anterior epidermis during C. elegans embryogenesis. Resistance of the epidermis to this force and to actomyosin-based circumferential constricting forces is mediated by FBN-1, a ZP domain protein related to vertebrate fibrillins. fbn-1 was required specifically within the epidermis and FBN-1 was expressed in epidermal cells and secreted to the apical surface as a putative component of the embryonic sheath. Tiling array studies indicated that fbn-1 mRNA processing requires the conserved alternative splicing factor MEC-8/RBPMS. The conserved SYM-3/FAM102A and SYM-4/WDR44 proteins, which are linked to protein trafficking, function as additional components of this network. Our studies demonstrate the importance of the apical extracellular matrix in preventing mechanical deformation of the epidermis during development.

Heart failure (HF) remains a public health concern as it is associated with high morbidity and death rates. In particular, heart failure with preserved ejection fraction (HFpEF) represents the dominant (>50%) form of HF and mostly occurring among postmenopausal women. Hence, the initiation and progression of the left ventricular diastolic dysfunctions (LVDD) (a typically clinical manifestation of HFpEF) in postmenopausal women have been attributed to estrogen deficiency and the loss of its residue cardioprotective effects. In this review, from a pathophysiological and immunological standpoint, we discuss the probable multiple pathomechanisms resulting in HFpEF, which are facilitated by estrogen deficiency. The initial discussions recap estrogen and estrogen receptors (ERs) and β-adrenergic receptors (βARs) signaling under physiological/pathological states to facilitate cardiac function/dysfunction, respectively. By reconciling these prior discussions, attempts were made to explain how the loss of estrogen facilitates the disruptions both ERs and βARs-mediated signaling responsible for; the modulation of intra-cardiomyocyte calcium homeostasis, maintenance of cardiomyocyte cytoskeletal and extracellular matrix, the adaptive regulation of coronary microvascular endothelial functions and myocardial inflammatory responses. By scaffolding the disruption of these crucial intra- and extra-cardiomyocyte physiological functions, estrogen deficiency has been demonstrated to cause LVDD and increase the incidence of HFpEF in postmenopausal women. Finally, updates on the advancements in treatment interventions for the prevention of HFpEF were highlighted.

The evaluation of nanomechanical properties of tissues in health and disease is of increasing interest to scientists. It has been confirmed that these properties, determined in part by the composition of the extracellular matrix, significantly affect tissue physiology and the biological behavior of cells, mainly in terms of their adhesion, mobility, or ability to mutate. Importantly, pathophysiological changes that determine disease development within the tissue usually result in significant changes in tissue mechanics that might potentially affect the drug efficacy, which is important from the perspective of development of new therapeutics, since most of the currently used in vitro experimental models for drug testing do not account for these properties. Here, we provide a summary of the current understanding of how the mechanical properties of brain tissue change in pathological conditions, and how the activity of the therapeutic agents is linked to this mechanical state.

Tissue homeostasis is perturbed by stressful events, which can lead to organ dysfunction and failure. This is particularly true for the heart, where injury resulting from myocardial infarction or ischemic heart disease can result in a cascading event ultimately ending with the loss of functional myocardial tissue and heart failure. To help reverse this loss of healthy contractile tissue, researchers have spent decades in the hopes of characterizing a cell source capable of regenerating the injured heart. Unfortunately, these strategies have proven to be ineffective. With the goal of truly understanding cardiac regeneration, researchers have focused on the innate regenerative abilities of zebrafish and neonatal mammals. This has led to the realization that although cells play an important role in the repair of the diseased myocardium, inducing cardiac regeneration may instead lie in the composition of the extra cellular milieu, specifically the extra cellular matrix. In this review we will briefly summarize the current knowledge regarding cell sources used for cardiac regenerative approaches, since these have been extensively reviewed elsewhere. More importantly, by revisiting innate cardiac regeneration observed in zebrafish and neonatal mammals, we will stress the importance the extra cellular matrix has on reactivating this potential in the adult myocardium. Finally, we will address how we can harness the ability of the extra cellular matrix to guide cardiac repair thereby setting the stage of next generation regenerative strategies.

In this present study, our aim was to evaluate the cell-mediated specific anti-donor antibody and its associated inflammatory cytokine secretion along with its succeeding effects on Nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Tissue from the NP compartment of 12 normal mice was isolated, expanded in cell culture, and the cell phenotypes were confirmed by flow cytometry. Multipotent differentiation and its specific gene expression analysis were confirmed by reverse transcriptase PCR. T and B cells were monitored for both donor and recipient mouse and further analysis of anti-donor antibody secretion was confirmed by lymphocyte crossmatch. In conjunction with anti-donor- specific antibody analysis, the associated inflammatory cytokine expression was analyzed by ELISA. In co-culture, cell-mediated antibody secretion was elevated in T and B cells positive mouse group, when compared to control mouse group. Allogeneic-derived donor NPMSCs were found to be stimulated the secretion of pro-inflammatory cytokines and the level of pro-inflammatory cytokines showed reduced expression in control mouse serum. In co-culture group the concentration of the cell-mediated pro-and anti-inflammatory cytokines found to be increased. Practical applications: Mesenchymal stem cell exhibit good regeneration capacity for many types of disease, and the mechanism belongs to regeneration is not clear. In intervertebral disc, the nucleus pulposus-derived mesenchymal stem cells showed a better regeneration capacity. On the contrary, the NP cells-based therapy, the Mesenchymal stem cells showed expanded anabolic and reduced catabolic activity together with induced anti-inflammatory effect. In this study, the T & B cells were used to evaluate the anti-donor antibody secretion and also to study how it stimulates the production of anti-donor antibodies against the donor cells. Finally, it was found that T & B cells lead the synthesis of inflammatory cytokines are IL-1, IL-6, and TNF-α. From this study, the results proved that the cell-mediated pro-and anti-inflammatory cytokines to be monitored in allogeneic stem cells-based therapy of intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.

A new injectable solution containing low-molecular-weight hyaluronic acid (HA) and a specific amino acid mixture was formulated with proper aesthetic performance for the main signs of facial skin photoaging. The present study aimed to investigate its new application for rejuvenating and augmenting labia majora using clinical and biometric assessments. Three sessions of intradermal injections were performed using 3 ml of test extracellular matrix (ECM) for 10 eligible post-menopause female subjects (age 53.6 ± 7.93 years). The effectiveness of the intervention was assessed by an independent physician using before-and-after pictures based on the physician's global assessment score. Objective biophysical skin assessments, including skin hydration, skin erythema, and melanin index, as well as elasticity parameters including firmness (R0), gross elasticity (R2), and net elasticity (R5), were also performed before the first injection and then on the 2nd and 12th weeks after the last session. Patients' satisfaction and all reported or observed adverse events were documented. At week 12, all the subjects reported an aesthetic improvement of 25% or more in rejuvenation and sagging of the labia major area. A statistically significant improvement was also detected in R0 and R5 at week 12 (p-values 0.005 and 0.022, respectively). Patient satisfaction surveys revealed a median score of 8 at both follow-up visits. The results showed a new indication of the tested HA ECM for providing a beneficial, durable, rejuvenating effect on the labia majora with a good safety profile., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ayatollahi et al.)

In children with Transposition of the Great Arteries (TGA), the pulmonary artery, and aorta are connected to the heart abnormally resulting in blue blood (deoxygenated) recirculating to the body and red blood (oxygenated) recirculating to the lungs. The arterial switch operation (ASO) is the standard of care for transposition of the great arteries (TGA), and given the low risk of early mortality and satisfactory long-term outcomes, focus is now on managing longer term complications such as neo-aortic root dilatation, and pulmonary artery stenosis. Since May 2016, we have used 2-ply extracellular matrix (ECM; Tyke) for reconstruction of the coronary button defects using a pantaloon patch. We present histology of implanted 2-ply ECM (Tyke) from a patient who went back to surgery for development of subaortic stenosis ~12 months after ASO.

The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeostasis. Vascular calcification is a major disruption to cardiovascular homeostasis, where tissues of the cardiovascular system undergo ectopic calcification and consequent dysfunction, but little is known about the expression of calcification genes in the healthy cardiovascular system. Large animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. We used RNA sequencing results from the sheep, which has been utilized extensively to examine calcification of prosthetic cardiac valves, to explore the transcriptome of the heart and cardiac valves in this large animal, in particular looking at expression of calcification and extracellular matrix genes. We then examined genes implicated in the process of vascular calcification in a wide array of cardiovascular tissues and across multiple developmental stages, using RT-qPCR. Our results demonstrate that there is a balance between genes that promote and those that suppress mineralization during development and across cardiovascular tissues. We show extensive expression of genes encoding proteins involved in formation and maintenance of the extracellular matrix in cardiovascular tissues, and high expression of hematopoietic genes in the cardiac valves. Our analysis will support future research into the functions of implicated genes in the development of valve calcification, and increase the utility of the sheep as a large animal model for understanding ectopic calcification in cardiovascular disease. This study provides a foundation to explore the transcriptome of the developing cardiovascular system and is a valuable resource for the fields of mammalian genomics and cardiovascular research.

The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeostasis. Vascular calcification is a major disruption to cardiovascular homeostasis, where tissues of the cardiovascular system undergo ectopic calcification and consequent dysfunction, but little is known about the expression of calcification genes in the healthy cardiovascular system. Large animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. We used RNA sequencing results from the sheep, which has been utilized extensively to examine calcification of prosthetic cardiac valves, to explore the transcriptome of the heart and cardiac valves in this large animal, in particular looking at expression of calcification and extracellular matrix genes. We then examined genes implicated in the process of vascular calcification in a wide array of cardiovascular tissues and across multiple developmental stages, using RT-qPCR. Our results demonstrate that there is a balance between genes that promote and those that suppress mineralization during development and across cardiovascular tissues. We show extensive expression of genes encoding proteins involved in formation and maintenance of the extracellular matrix in cardiovascular tissues, and high expression of hematopoietic genes in the cardiac valves. Our analysis will support future research into the functions of implicated genes in the development of valve calcification, and increase the utility of the sheep as a large animal model for understanding ectopic calcification in cardiovascular disease. This study provides a foundation to explore the transcriptome of the developing cardiovascular system and is a valuable resource for the fields of mammalian genomics and cardiovascular research. [ABSTRACT FROM AUTHOR]

A major challenge in the chronic wound healing is a self-care wound dressing. The problem in chronic wounds is the lack of functional extracellular matrix to stimulate healing. The extracellular matrix is a network of proteins and polysaccharides that serves as physical framework and provides regulatory signals. The primary goal is to mimic the property of the extracellular matrix with Silk Fibroin and Paramylon to produce a novel bioactive film. Silk fibroin is a fibrous protein having unique mechanical properties and tunable biodegradability that makes it favourable for tailoring to specific applications. Paramylon is a β-glucan that possess a broad spectrum of biological activity that enhances the immune response. Silk fibroin/paramylon blend films have been prepared by solution casting and were examined for structural, thermal, mechanical and other physical properties for knowing its transformation for chronic wound healing. It was observed that the fibroin films shows high thermal stability, high hydrophobicity, high stiffness value whereas the paramylon film show good water absorption property and both fibroin and paramylon shows good blood compatibility and was non-toxic as well. It also confirms that the blended films showed a combination of fibroin and paramylon property at different concentrations without any chemical interaction. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common cancers in the world with a high ratio of mortality. Regarding the late diagnosis, there is a high ratio of distant metastasis among GC cases. Despite the recent progresses in therapeutic modalities, there is not still an efficient therapeutic method to increase survival rate of metastatic GC cases. Main body: Apart from the various intracellular signaling pathways which are involved in tumor cell migration and metastasis, the local microenvironment is also a critical regulator of tumor cell migration. Indeed, the intracellular signaling pathways also exert their final metastatic roles through regulation of extra cellular matrix (ECM). Therefore, it is required to assess the role of extra cellular components in biology of GC. Conclusion: In the present review, we summarize 48 of the significant ECM components including 17 ECM modifying enzymes, seven extracellular angiogenic factors, 13 cell adhesion and cytoskeletal organizers, seven matricellular proteins and growth factors, and four proteoglycans and extra cellular glycoproteins. This review paves the way of determination of a specific extra cellular diagnostic and prognostic panel marker for the GC patients. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) proteins form the structural support for migration of leukocytes and provide multiple signals to assist in their functions during inflammatory conditions. Presence of pro-inflammatory mediators in the tissues results in the remodelling of matrices which could modify the functions of extravasated leukocytes. Previous reports have shown changes in the expression of ECM proteins during local inflammatory responses. In this study, we have investigated the time- and tissue-specific expression profile of key ECM proteins in systemic inflammation using lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP) mouse models. The results show that compared to naïve tissues, within 12 h following CLP surgery, a 20–30-fold increase was observed in the expression of collagen-IV (Col-IV) transcripts in the mesentery tissues with a 2.4-fold increase in the protein by 24 h. However, Western blot band intensities indicated that vimentin and fibrinogen were remarkably expressed in more quantity compared to Col-IV. Secondly, in CLP group of mice, fibrinogen showed 6–40-fold increase in mRNA level in various tissues with about 2-fold increase in the protein level compared to respective naïve tissues. Similar studies in the LPS-injected mice showed up to 2–3 fold increase in the expression of Col-IV, fibrinogen and vimentin at protein level in the lungs. In such animals, although similar pattern was observed for fibrinogen in kidney and liver tissues, the mesentery showed prominent changes in Col-IV and vimentin mRNA compared to CLP. Further, bioinformatics analysis showed multiple pathways which could be associated with vimentin, Col-IV and fibrinogen under inflammatory conditions both in human and mouse. The current study will help in better understanding of possible signalling from ECM proteins in inflammatory microenvironment and may contribute in development of cell adhesion-based therapeutics. [ABSTRACT FROM AUTHOR]

Context: Matrix metalloproteinases (MMPs) are involved in the remodelling of the glomerular basement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM) of the GBM. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, Scopus and Web of Science have been searched. Results: Gelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS), which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases (TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP, all the other types of NS showed conflicting results. Both suppression and induction of MMPs are finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover and matrix accumulation. The review compiled the mechanisms of action of both downregulation and upregulation of MMPs. Conclusions: Imbalance of ECM metabolism due to varied expression levels and activities of MMPs in different types of primary NS might contribute to the progression of nephropathies. Further studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/ therapeutic tool.