Matrix Molecules Research Articles

Serum integrin accumulation during asthma exacerbation: The role of matrix metalloproteinases.

The inflammation caused by asthma exacerbation can lead to permanent changes in the airways and loss of lung function. Integrins are membrane receptors that interact with components of the extracellular matrix and cell adhesion molecules. It is known that these receptors can be found in soluble form in some conditions such as asthma, but it is unknown if exacerbation during asthma leads to soluble integrins. Our results indicated that asthma patients showed higher levels of soluble α1, α2, and β2 integrin subunits in their serum compared to controls, as confirmed by both ELISA and western blot. During asthma exacerbation, the levels of α2 and β2 integrin subunits increased even more compared to non-exacerbation and controls, while the α1 integrin subunit decreased. Western blot analysis identified two β2 integrin subunits, one at 75 kDa and another at 120 kDa; the 120 kDa subunit increased during asthma exacerbation. The activity of matrix metalloproteinase 9 (MMP9) increased during exacerbation, while MMP2 remained unchanged. Lower forced expiratory volume in 1 second (FEV1) values were associated with higher expression levels of α2, β1, and β2 integrin subunits. Active and latent MMP9 were correlated with the levels of the β2 integrin subunit, which means that at low levels of active and latent MMP9, there are lower levels of β2 integrin subunit. In conclusion, asthma exacerbation leads to the presence of soluble integrins, particularly the β2 subunit, most likely due to MMP9-induced proteolytic cleavage.

Effects of Conditioned Media From Human Umbilical Cord-Derived Mesenchymal Stem Cells on Tenocytes From Degenerative Rotator Cuff Tears in an Interleukin 1β-Induced Tendinopathic Condition.

Evidence suggests that mesenchymal stem cells (MSCs) are safe for treating different tendinopathies. Synovial fluid is a pooled environment of biomarkers from the inflammatory and degenerative joint cavity. Understanding the effects of synovial fluid on MSCs is important, as it is the first microenvironment that administered MSCs encounter. Several studies have reported that exposure to osteoarthritic synovial fluid-activated MSCs increased the release of soluble factors; however, the paracrine effects of shoulder synovial fluid-stimulated umbilical cord-derived MSCs (SF-UC-MSCs) on tendinopathy have yet to be investigated. To assess the effects of the conditioned media from SF-UC-MSCs on tenocytes from degenerative rotator cuff tears in an interleukin-1β (IL-1β)-induced tendinopathic condition. Controlled laboratory study. UC-MSCs were isolated and cultured from healthy, full-term deliveries by cesarean section. Tenocytes were isolated and cultured from patients with degenerative rotator cuff tears. Conditioned media were obtained from UC-MSCs stimulated with synovial fluid. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, matrix molecules, and growth factors, the tenocytes were cultured with IL-1β and 50% of the conditioned media from the SF-UC-MSCs; quantitative, real-time, reverse transcriptase polymerase chain reaction was also performed. A prostaglandin E2 (PGE2) assay was performed to investigate the PGE2 level secreted by the tenocytes. Western blotting was performed to examine protein synthesis of collagen type I and III. Cell viability, senescence, and apoptosis assays were also performed. The conditioned media from the SF-UC-MSCs interfered with the inflammatory gene expression on tenocytes induced by IL-1β, but it increased the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3. Meanwhile, the conditioned media decreased the PGE2 level on cells induced by IL-1β. It did increase the type I/III ratio of gene expression and protein synthesis, mainly through the induction of type I collagen. Conditioned media of SF-UC-MSCs reversed senescence and apoptosis induced by IL-1β. Study findings indicated that the conditioned media from SF-UC-MSCs had anti-inflammatory effects and cytoprotective effects on IL-1β-treated tenocytes from degenerative rotator cuff tears. UC-MSCs have useful potential for the treatment of tendinopathy in practice.

Enhanced Microwave Absorption in Organogels:The Synergy of Polar Molecules and Magnetic Particles

Herein, wideband microwave absorbing materials with high flexibility are developed by creating a novel layered organogel composite consisting of carbonyl iron particles (CIP) and polyacrylamide (PAM), employing ethylene glycol (EG) as the solvent. The microwave absorbing properties of layered absorbers with different CIP contents are investigated over the 1–18GHz range. An integrated stratified architecture was obtained using polar EG molecules and magnetic CIP particles, which were the main contributors to magnetic and dielectric losses in the PAM matrix. The results indicated that the minimum reflection loss reaches a value of −48.0dB at a thickness of 2mm and a frequency of 15.5GHz; meanwhile, an effective absorption bandwidth of 3.2GHz in the C-band can also be obtained. An analysis of the absorption mechanism shows that the combination of an impedance-matching layer composed of CIP magnetic particles and an absorption layer composed of EG polar molecules in the PAM matrix provides strong broadband absorption in the C-band. Overall, the CIP/EG@PAM organogel composites have simple preparation, high flexibility, and it has adhesion. This study provides a new strategy for designing wideband microwave absorbing materials.

DPP an extracellular matrix molecule induces Wnt5a mediated signaling to promote the differentiation of adult stem cells into odontogenic lineage

Dentin phosphophoryn (DPP) an extracellular matrix protein activates Wnt signaling in DPSCs (dental pulp stem cells). Wnt/β catenin signaling is essential for tooth development but the role of DPP-mediated Wnt5a signaling in odontogenesis is not well understood. Wnt5a is typically considered as a non-canonical Wnt ligand that elicits intracellular signals through association with a specific cohort of receptors and co-receptors in a cell and context–dependent manner. In this study, DPP facilitated the interaction of Wnt5a with Frizzled 5 and LRP6 to induce nuclear translocation of β-catenin. β-catenin has several nuclear binding partners that promote the activation of Wnt target genes responsible for odontogenic differentiation. Interestingly, steady increase in the expression of Vangl2 receptor suggest planar cell polarity signaling during odontogenic differentiation. In vitro observations were further strengthened by the low expression levels of Wnt5a and β-catenin in the teeth of DSPP KO mice which exhibit impaired odontoblast differentiation and defective dentin mineralization. Together, this study suggests that the DPP-mediated Wnt5a signaling could be exploited as a therapeutic approach for the differentiation of dental pulp stem cells into functional odontoblasts and dentin regeneration.

Biofilm matrix: a multifaceted layer of biomolecules and a defensive barrier against antimicrobials.

Bacterial cells often exist in the form of sessile aggregates known as biofilms, which are polymicrobial in nature and can produce slimy Extracellular Polymeric Substances (EPS). EPS is often referred to as a biofilm matrix and is a heterogeneous mixture of various biomolecules such as polysaccharides, proteins, and extracellular DNA/RNA (eDNA/RNA). In addition, bacteriophage (phage) was also found to be an integral component of the matrix and can serve as a protective barrier. In recent years, the roles of proteins, polysaccharides, and phages in the virulence of biofilms have been well studied. However, a mechanistic understanding of the release of such biomolecules and their interactions with antimicrobials requires a thorough review. Therefore, this article critically reviews the various mechanisms of release of matrix polymers. In addition, this article also provides a contemporary understanding of interactions between various biomolecules to protect biofilms against antimicrobials. In summary, this article will provide a thorough understanding of the functions of various biofilm matrix molecules.

Measuring the electric dipole moment of the electron using polar molecules in a parahydrogen matrix

This paper outlines the groundwork we have done in preparation for our proposed experiment to measure the electric dipole moment of the electron in barium monofluoride molecules within a cryogenic parahydrogen matrix. We describe the experimental setup we use to grow and characterize the cryogenic crystals and produce a molecular source of barium monofluoride. The technique we present has the potential to improve the sensitivity to the electric dipole moment of the electron by increasing the number of molecules under measurement without affecting their spin coherence times. If successful, this approach would represent a significant advancement in precision measurements using molecules in cryogenic solid matrices.

Targeting the MAtrix REgulating MOtif abolishes several hallmarks of cancer, triggering antitumor immunity

Tumor-targeted therapies have often been inefficient due to the lack of concomitant control over the tumor microenvironment. Using an immunocompetent autologous breast cancer model, we investigated a MAtrix REgulating MOtif (MAREMO)-mimicking peptide, which inhibits the protumorigenic extracellular matrix (ECM) molecule tenascin-C that activates several cancer hallmarks. In cultured cells, targeting the MAREMO blocks tenascin-C signaling involved in cell adhesion and immune-suppression by inhibiting tenascin-C interactions with fibronectin, TGFβ, CXCL12, and others, thereby blocking downstream events. Using RNASequencing and various genetic, molecular, in situ, and in vivo assays, we demonstrate that the MAREMO peptide similarly blocks multiple tenascin-C functions in vivo. This includes releasing tumor-infiltrating leukocytes, including CD8+ T cells, from the stroma. The MAREMO peptide also triggers interferon signaling, restoring antitumor immunity, contributing to tumor growth inhibition and reduced dissemination. The MAREMO peptide targets tumor cells directly by promoting growth suppression and inhibiting phenotypic plasticity, subsequently enhancing responsiveness to the endogenous death inducer tumor necrosis factor-related apoptosis-inducing ligand, as shown by a loss-of-function approach. Moreover, the MAREMO peptide largely subdues the tumor bed by depleting fibroblasts, repressing tenascin-C and other ECM molecules, and restoring the function of the few remaining blood vessels. In conclusion, targeting tenascin-C with a MAREMO peptide represents a powerful anticancer strategy with a broad inhibition of several cancer hallmarks.

Biofilm morphology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) on poly-D,L-lactide-co-poly(ethylene glycol) (PDLLA-PEG) coated titanium

Biodegradable polymeric coatings are being explored as a preventive strategy for orthopaedic device-related infection. In this study, titanium surfaces (Ti) were coated with poly-D,L-lactide (PDLLA, (P)), polyethylene-glycol poly-D,L-lactide (PEGylated-PDLLA, (PP20)), or multi-layered PEGylated-PDLLA (M), with or without 1 % silver sulfadiazine. The aim was to evaluate their cytocompatibility, resistance to Staphylococcus aureus biofilm formation, and their potential to enhance the susceptibility of any biofilm formed to antibiotics. Using automated high-content screening confocal microscopy, biofilm formation of a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate expressing GFP was quantified, along with isogenic mutants that were unable to form polysaccharidic or proteinaceous biofilm matrices. The results showed that PEGylated-PDLLA coatings exhibited significant antibiofilm properties, with M showing the highest effect. This inhibitory effect was stronger in S. aureus biofilms with a matrix composed of proteins compared to those with an exopolysaccharide (PIA) biofilm matrix. Our data suggest that the antibiofilm effect may have been due to (i) inhibition of the initial attachment through microbial surface components recognising adhesive matrix molecules (MSCRAMMs), since PEG reduces protein surface adsorption via surface hydration layer and steric repulsion; and (ii) mechanical disaggregation and dispersal of microcolonies due to the bioresorbable/degradable nature of the polymers, which undergo hydration and hydrolysis over time. The disruption of biofilm morphology by the PDLLA-PEG co-polymers increased S. aureus susceptibility to antibiotics like rifampicin and fusidic acid. Adding 1 % AgSD provided additional early bactericidal effects on both biofilm and planktonic S. aureus. Additionally, the coatings were cytocompatible with immune cells, indicating their potential to enhance bacterial clearance and reduce bacterial colonisation of titanium-based orthopaedic biomaterials.

Identification and Validation of a Threshold for Early Posttransplant Bronchoalveolar Fluid Hyaluronan that Distinguishes Lung Recipients at Risk for CLAD

BackgroundFew tools exist for early identification of patients at risk for chronic lung allograft dysfunction (CLAD). We previously showed hyaluronan (HA), a matrix molecule that regulates lung inflammation and fibrosis, accumulates in bronchoalveolar lavage fluid (BALF) and blood in CLAD. We aimed to determine if early posttransplant HA elevations inform CLAD risk. MethodsHA was quantified in 3080 BALF and 1323 blood samples collected over the first posttransplant year in 743 adult lung recipients at 5 centers. The relationship between BALF or blood HA and CLAD was assessed using Cox models with a time-dependent binary covariate for “elevated” HA. Potential thresholds for elevated HA were examined using a grid search between the 50th and 85th percentile. The optimal threshold was identified using fit statistics, and the association between the selected threshold and CLAD was internally validated through iterative resampling. A multivariable Cox model using the selected threshold was performed to evaluate the association of elevated HA with CLAD considering other factors that may influence CLAD risk. ResultsBALF HA levels >19.1ng/mL (65th percentile), had the largest hazard ratio for CLAD (HR 1.70, 95% CI 1.25–1.31; p<0.001), optimized fit statistics, and demonstrated robust reproducibility. In a multivariable model, the occurrence of BALF HA >19.1 ng/mL in the first posttransplant year conferred a 66% increase in the hazards for CLAD (adjusted HR 1.66, 95% CI 1.19–2.32; p=0.003). Blood HA was not significantly associated with CLAD. ConclusionsWe identified and validated a precise threshold for BALF HA in the first posttransplant year that distinguishes patients at increased CLAD risk.

Cellular fibronectin-targeted fluorescent aptamer probes for early detection and staging of liver fibrosis

Liver fibrosis is a key process in the progression of chronic liver disease to cirrhosis. Currently, early diagnosis and precise staging of liver fibrosis remain great challenges. Extracellular matrix (ECM) molecules expressed specifically during liver fibrosis are ideal targets for bioimaging and detection of liver fibrosis. Here, we report that fluorescent probes based on a nucleic acid aptamer (ZY-1) targeting cellular fibronectin (cFN), a critical ECM molecule significantly accumulating during liver fibrosis, are promising bioimaging agents for the staging of liver fibrosis. In the work, the outstanding binding affinity of ZY-1 to cFN was validated through an in vitro model of human-derived hepatic stellate cells (HSCs). Subsequently, we constructed different ZY-1-based fluorescent probes and explored the real-time imaging performance of these fluorescent probes in CCl4-induced mouse models of different liver fibrosis stages. The ZY-1-based fluorescent probes, for the first time, effectively identified and distinguished early-stage liver fibrosis (stage 3 of Ishak 6) from advanced liver fibrosis (stage 5 of Ishak 6). The proof-of-concept study provides compelling evidences that ZY-1-based probes are a promising tool for the early diagnosis and staging of liver fibrosis and paves the way for further development of clinical-related diagnosis strategies for fibrotic diseases of the liver and other organs. Statement of significanceCurrently, early diagnosis and accurate staging of liver fibrosis continue to present significant challenges. This study demonstrates that fluorescent probes based on the nucleic acid aptamer ZY-1, which targets cellular fibronectin (cFN)—a crucial extracellular matrix (ECM) molecule that significantly accumulates during liver fibrosis—are promising bioimaging agents for staging liver fibrosis. The ZY-1-based fluorescent probes effectively identified and differentiated early-stage liver fibrosis from advanced liver fibrosis. This proof-of-concept study not only provides compelling evidence that ZY-1-based probes show promise for the early diagnosis and staging of liver fibrosis but also paves the way for further investigations into the use of ZY-1 in detecting other diseases associated with cFN.

Design of epoxy composites via molecular orbital modulation and enhanced π-πF interactions achieving synchronous improvement of electrical and mechanical performance

The stacked aromatic rings in bisphenol A epoxy resins provide good mechanical properties and thermal stability while leading to the transport of conjugated delocalized electrons, which dramatically affects the insulation properties of the material. This contradiction leads to performance bottlenecks in epoxy-based encapsulation materials, further limiting the development of high-voltage semiconductor devices. In this study, fluorophenyl-modified epoxy monomers (FPMEPs) are designed to enrich the intermolecular interactions in an aromatic system while inhibiting the charge transport process, thereby solving the contradiction between the electrical and mechanical properties. Firstly, FPMEP with high insulation properties was designed by theoretical calculations and then synthesized by highly selective click chemistry. The fluorophenyl modulates the molecular orbitals of epoxy monomers and acts as a deep trap to inhibit charge injection and transport processes. Further, the π-πF stacking between the aromatic system and fluorophenyl enhances the interaction of the matrix molecules and solves the dispersion problem of fluorinated graphene (FG) fillers. The FPMEP/FG composites thus exhibit a considerable improvement in electrical and mechanical properties (breakdown strength of 39.8 kV/mm, dielectric loss of 0.011@50 Hz, tensile strength of 68.8 MPa, and adhesive strength of 2.15 MPa), and demonstrate good water repellency and aging durability. This matrix-filler synergistic modification strategy provides new insights into the design of insulation material.

Visualizing multimerization of plasticity-related gene 5 at the plasma membrane using FLIM-FRET.

Plasticity-related gene (PRG) 5 is a vertebrate specific membrane protein, that belongs to the family of lipid-phosphate phosphatases (LPPs). It is prominently expressed in neurons and is involved in cellular processes such as growth-cone guidance and spine formation. At a functional level, PRG5 induces filopodia in non-neuronal cell lines, as well as the formation of plasma membrane protrusions in primary cortical and hippocampal neurons. Overexpression of PRG5 in immature neurons leads to the induction of spine-like structures, and regulates spine density and morphology in mature neurons. Understanding spine formation is pivotal, as spine abnormalities are associated with numerous neurological disorders. Although the importance of PRG5 in neuronal function is evident, the precise mechanisms as to how exactly it induces membrane protrusions and orchestrates cellular processes remain unresolved. Here we used in vitro biochemical assays to demonstrate that in HEK293T cells a large fraction of PRG5 can be found in homo dimers and lager multimers. By using Fluorescence Lifetime Imaging (FLIM) to quantify Förster Resonance Energy Transfer (FRET), we were able to visualize and quantify the specific localization of PRG5 multimers in living HEK293T cells and in fixed immature primary hippocampal neurons. Here, we provide the first evidence that PRG5 multimers are specifically localized in non-neuronal filopodia, as well as in neuronal spine-like structures. Our findings indicate a potential functional role for PRG5 multimerization, which might be required for interaction with extracellular matrix molecules or for maintaining the stability of membrane protrusions.

Continuous Biosensor Based on Particle Motion: How Does the Concentration Measurement Precision Depend on Time Scale?

Continuous biosensors measure concentration-time profiles of biomolecular substances in order to allow for comparisons of measurement data over long periods of time. To make meaningful comparisons of time-dependent data, it is essential to understand how measurement imprecision depends on the time interval between two evaluation points, as the applicable imprecision determines the significance of measured concentration differences. Here, we define a set of measurement imprecisions that relate to different sources of variation and different time scales, ranging from minutes to weeks, and study these using statistical analyses of measurement data. The methodology is exemplified for Biosensing by Particle Motion (BPM), a continuous, affinity-based sensing technology with single-particle and single-molecule resolution. The studied BPM sensor measures specific small molecules (glycoalkaloids) in an industrial food matrix (potato fruit juice). Measurements were performed over several months at two different locations, on nearly 50 sensor cartridges with in total more than 1000 fluid injections. Statistical analyses of the measured signals and concentrations show that the relative residuals are normally distributed, allowing extraction and comparisons of the proposed imprecision parameters. The results indicate that sensor noise is the most important source of variation followed by sample pretreatment. Variations caused by fluidic transport, changes of the sensor during use (drift), and variations due to different sensor cartridges and cartridge replacements appear to be small. The imprecision due to sensor noise is recorded over few-minute time scales and is attributed to stochastic fluctuations of the single-molecule measurement principle, false-positive signals in the signal processing, and nonspecific interactions. The developed methodology elucidates both time-dependent and time-independent factors in the measurement imprecision, providing essential knowledge for interpreting concentration-time profiles as well as for further development of continuous biosensing technologies.

Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair.

Olfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair and axonal regeneration.

The Effects of Substrates and Sonication Methods on the Antioxidant Activity of Kefir Postbiotics

Sonoporation stimulates cell growth as it improves the permeability of the membrane and increases the uptake of impermeable molecules in the extracellular matrix. We evaluated the effects of substrates (whey, whole, and skim milk) and ultrasonic treatments (ultrasonication and thermosonication) on the antioxidant activity (AA) of water-soluble kefir postbiotics (WSKPs). The samples were evaluated in terms of antioxidant activity (ABTS, DPPH, FRAP, and ORAC), water-soluble protein content, proteolysis (SDS-PAGE profiles), and cell membrane permeability. The levels of AA in all WSKPs depended on the substrate and method of obtaining them. However, the WSKPs from whey had higher antioxidant activity with DPPH (11.11 mg TE/100 mL), ABTS (12.77 mg TE/100 mL), and FRAP (5.18 mg TE/100 mL). Also, the WSKPs from whey had the highest values for water-soluble protein (1.45–1.32 mg/mL) and proteolysis degree and the lowest percentage of dead cells (11.4–28%). These results suggest that the production of WSKPs from whey might add value to whey production. Furthermore, WSKPs have potential as a functional ingredient in the production of beverages or foods with antioxidant activity.

Elastin-like polypeptide-functionalized nanobody for column-free immunoaffinity purification of aflatoxin B1.

A column-free immunoaffinity purification (CFIP) technique for sample preparation of aflatoxin B1 (AFB1) was developed using an AFB1-specific nanobody (named G8) and an elastin-like polypeptide (ELP). The reversible phase transition between liquid and solid in response to temperature changes was exhibited by the ELP which was derived from human elastin. The G8 was tagged with ELPs of various lengths (20, 40, 60, and 80 repeat units) at the C-terminus using recursive directional ligation (RDL). Coding sequences were then subcloned into pET30a at the multiple cloning sites. Bioactive recombinant proteins were produced by expressing them as inclusion bodies in Escherichia coli BL21 (DE3), then dissolved and refolded. Analysis by indirect competitive enzyme-linked immunosorbent assay (icELISA) and transition temperature (Tt) measurement confirmed that the refolded G8-ELPs preserved the ability to recognize AFB1 as well as phase transition when the temperature rose above Tt. To establish the optimal conditions for cleaning AFB1, the effects of various parameters on recovery were investigated. The recovery in ELISA tests was 95 ± 3.67% under the optimized CFIP workflow. Furthermore, the CFIP-prepared samples were applied for high-performance liquid chromatography (HPLC) detection. The recovery in the CFIP-HPLC test ranged from 54 ± 1.86% to 98 ± 3.58% for maize, rice, soy sauce, and vegetable oil samples. To the best of our knowledge, this is the first report combining the function of both nanobody and ELP to develop a cleanup technique for small molecules in a complex matrix. The CFIP for the sample pretreatment was easy to use and inexpensive. In contrast to conventional immunosensitivity materials, the reagent utilized in the CFIP was entirely biosynthesized without any chemical coupling reactions. This suggests that the nanobody-ELP may serve as a useful dual-functional reagent for the development of sample cleaning or purification methods.

Efficacy of Intra-articular Platelet-rich Plasma versus Hydrocortisone with Local Anaesthetic Injection in Temporomandibular Joint Disorders - A Prospective Study

Abstract Introduction: Temporomandibular joint (TMJ) is subjected to many disorders commonly termed temporomandibular disorders (TMDs) which include TMJ hypermobility, ankylosis and internal derangement. In the past, many non-invasive conservative treatment modalities were tried out for their treatment which include joint unloading, the use of anti-inflammatory agents and physiotherapy. In recent times, injections of corticosteroids and platelet-rich plasma (PRP) into the TMJ have been proposed as alternative therapeutic methods. The main objective of the prospective study was to compare the efficacy of intra-articular injection of PRP and hydrocortisone with local anaesthetic agents in reducing the symptoms in patients with TMDs. Materials and Methods: This prospective study included 30 patients with TMDs, out of which 15 patients (Group I) received PRP injections and 15 patients (Group II) received hydrocortisone with local anaesthetics for arthrocentesis in their affected joints. The patients were assessed for pain, maximum interincisal mouth opening, TMJ sound and disc displacement. Results: The pain was markedly reduced in patients who received PRP injections (Group I) as compared to those who received hydrocortisone injection (Group II). An increase in mouth opening was similar in both the groups, and TMJ sounds were reduced in patients who received PRP. Magnetic resonance imaging also showed that PRP-treated patients showed better articular disc repair than patients treated with hydrocortisone. Discussion: PRP increases chondrocyte proliferation and production of matrix molecules and helps maintain the integrity of the chondral surface, thereby facilitating joint movement, whereas corticosteroids are more potent anti-inflammatory agents and they act by inhibiting prostaglandin synthesis which is the mediator of inflammation. Thus, the use of PRP has been proven to show better results in reducing the symptoms of TMDs and also helped in articular disc repair.

Matrix Metalloproteinases on Skin Photoaging.

Skin aging is characterized by an imbalance between the generation and degradation of extracellular matrix molecules (ECM). Matrix metalloproteinases (MMPs) are the primary enzymes responsible for ECM breakdown. Intrinsic and extrinsic stimuli can induce different MMPs. However, there is limited literature especially on the summary of skin MMPs and potential inhibitors. We aim to focus on the upregulation of MMP expression or activity in skin cells following exposure to UV radiation. We also would like to offer valuable insights into potential clinical applications of MMP inhibitors for mitigating skin aging. This article presents the summary of prior research, which involved an extensive literature search across diverse academic databases including Web of Science and PubMed. Our findings offer a comprehensive insight into the effects of MMPs on skin aging after UV irradiation, including their substrate preferences and distinct roles in this process. Additionally, a comprehensive list of natural plant and animal extracts, proteins, polypeptides, amino acids, as well as natural and synthetic compounds that serve as inhibitors for MMPs is compiled. Skin aging is a complex process influenced by environmental factors and MMPs. Research focuses on UV-induced skin damage and the formation of Advanced Glycosylation End Products (AGEs), leading to wrinkles and impaired functionality. Inhibiting MMPs is crucial for maintaining youthful skin. Natural sources of MMP inhibitor substances, such as extracts from plants and animals, offer a safer approach to obtain inhibitors through dietary supplements. Studying isolated active ingredients can contribute to developing targeted MMP inhibitors.

Regulation of TGF-β1-induced fibroblast differentiation of human periodontal ligament stem cells through the mutually antagonistic action of ectonucleotide pyrophosphatase/phosphodiesterase 1 and 2.

Human periodontal ligament stem cells (hPDLSCs) differentiate into periodontal ligament (PDL) fibroblasts, osteoblasts, and cementoblasts. To identify inducers of PDL fibroblastic differentiation, monoclonal antibody series were developed a series of against membrane/extracellular matrix (ECM) molecules through decoy immunization. The anti-PDL13 antibody targets ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), renowned for regulating skeletal and soft tissue mineralization. ENPP1 accumulates in the periodontal ligament region of tooth roots, and specifically localizes to the cell boundaries and elongated processes of the fibroblastic cells. As ENPP1 expression increases during fibroblastic differentiation, mineralization induced by tissue-nonspecific alkaline phosphatase (TNAP), a pyrophosphate-degrading enzyme, is completely inhibited. This is consistent with ENPP1 and TNAP acting in opposition, and TGF-β1-induced ENPP1 expression creates an essential environment for PDL fibroblast differentiation. Representative fibroblastic differentiation markers decrease with endogenous ENPP1 inhibition by siRNA and antibody blocking. ENPP2 generates lipid signaling molecules. In contrast to ENPP1, ENPP2 disappears in TGF-β1-induced PDL fibroblasts. Ectopic expression of ENPP2 hinders TGF-β1-induced PDL fibroblastic differentiation. Suppression of ENPP1 and ENPP2 leads to severe defects in undifferentiated and differentiated cells, demonstrating that these two factors play opposing roles in soft and hard tissue differentiation but can complement each other for cell survival. In conclusion, increased ENPP1 is crucial for TGF-β1-induced PDL differentiation, while ENPP2 and TNAP can inhibit ENPP1. ENPP1 and ENPP2 exhibit complementary functions in the cell survival.

Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.

Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger β1 integrin activation and instead actuate a TGF-β1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.