Extracellular Matrix Proliferation Research Articles

Research Progress on the Antifibrotic Activity of Traditional Chinese Medicine Polysaccharides.

Fibrosis is a pathological process characterized by excessive extracellular matrix (ECM) deposition and proliferation fibrous tissue, a condition associated with various chronic diseases, such as liver cirrhosis, inflammation of the lungs, and myocarditis. Clinical treatment options for fibrotic diseases are currently limited and have poor efficacy. However, recent studies have increasingly demonstrated that polysaccharides exhibit significant antifibrotic activity by modulating cell proliferation and migration, inhibiting inflammation and oxidative stress associated fibrosis and regulating gut microbiota. This review provides an overview of recent advances in polysaccharide research for antifibrosis and offers new perspectives on the treatment of fibrotic diseases.

The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era.

Double expression (DE) is a World Health Organization-recognized adverse prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double-expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression-free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non-DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA-sequencing analyses exhibited upregulation in tumor proliferation-related pathways in DEL patients, but downregulation in extracellular matrix organization, T-cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients.

The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. Transforming growth factor β (TGFβ) can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGFβ-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc. Genes related to TGFβ pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing. Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGFβ induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGFβ-mediated fibroblasts with up-regulation of CRISPLD2. CRISPLD2 was found increased reactivity in TGFβ induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGFβ induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.

Abstract We140: Age-Dependent miR-34a and AGTRAP Cross-Modulation: a Novel Mechanism of Vascular Aging

Background: Renin-Angiotensin Aldosterone System (RAAS) activation plays a central role in vascular aging, leading to structural and functional alterations including vascular smooth muscle cell (VSMC) proliferation, migration and secretion of extracellular matrix and inflammatory molecules. The age-associated increase in Angiotensin II (Ang II) expression enhances AT1-receptor activity and determinates a pro-fibrotic and pro-inflammatory phenotype. Further, miR-34a expression is modulated by aging and increases in different tissues, including the mouse aorta, but no direct miR-34a target has been identified in the RAAS pathway that sustains age-dependent increase of pro-inflammatory signaling. Aims: The aim of our study is to evaluate the potential interaction between miR-34a and RAAS signaling in VSMCs. Methods and Results: miR-34a expression exhibited an age-dependent increase in Rhesus Monkey (8- to 26-year-old) and rat central arteries (8- and 30-month-old). In silico analysis indicated that AT1R-associated protein (AGTRAP), a negative modulator of AT1R signaling, is a potential miR-34a target suggesting that the age-dependent increase in miR-34a in the arterial vascular wall may decrease AGTRAP expression in arterial VSMC. Ang II enhanced miR-34a expression in 30-month-old rat and in human aorta SMCs (HASMCs), whereas AGTRAP and Sirtuin-1 (SIRT1) mRNA and protein level decreased. Immunohistochemistry analysis showed a decrease of AGTRAP in 18-month-old miR-34a knock-out mice compared to 2-month-old mice. By luciferase assay, we demonstrated that AGTRAP is a direct miR-34a target. Moreover, AGTRAP and SIRT1 decreased in HASMCs infected with miR-34a-encoding lentivirus and this effect was partially rescued in AGTRAP/miR-34a co-infected cells. Finally, pro-inflammatory genes IL-6, COX-2, MCP-1 and MFG-E8 expression was upregulated in Ang II-treated and miR-34a overexpressing HASMCs, and this effect was abolished in AGTRAP/miR-34a co-transfected cells. Conclusions: Our results show cross-modulation between miR-34a and AGTRAP. MiR-34a targeting AGTRAP increases the expression of pro-inflammatory molecules in VSMCs and represents a novel mechanism that modulates RAAS signaling in vascular aging. Statement: This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.

Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks.

There is a lack of effective treatment options for diabetic refractory wounds, which presents a critical clinical issue that needs to be addressed urgently. Our research has demonstrated that human placenta-derived mesenchymal stem cells (plaMSCs) facilitate the migration and proliferation of HaCat cells, thereby enhancing diabetic wound healing primarily via the exosomes derived from plaMSCs (plaMSCs-Ex). Using label-free proteomics, plaMSCs and their exosomes were analysed for proteome taxonomic content in order to explore the underlying effective components mechanism of plaMSCs-Ex in diabetic wound healing. Differentially expressed proteins enriched in plaMSCs-Ex were identified and underwent bioinformatics analysis including GO annotation, KEGG pathway enrichment, gene set enrichment analysis (GSEA) and protein-protein interaction analysis (PPI). Results showed that the proteins enriched in plaMSCs-Ex are significantly involved in extracellular matrix organisation, epithelium morphogenesis, cell growth, adhesion, proliferation and angiogenesis. PPI analysis filtered 2 wound healing-related clusters characterised by hub proteins such as POSTN, FN1, SPARC, TIMP1, SERPINE1, LRP1 and multiple collagens. In brief, the exosomal proteins derived from plaMSCs reveal diverse functions of regeneration and tissue remodelling based on proteomics analysis and potentially play a role in diabetic wound healing.

Dual-wavelength dye laser combined with betamethasone injection for treatment of keloids: protocol of a randomised controlled trial

IntroductionKeloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the...

Repeated Silica exposures lead to Silicosis severity via PINK1/PARKIN mediated mitochondrial dysfunction in mice model

Background and objectivesSilicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in lungs are linked to silicosis development. Mitochondrial dysfunction plays critical role in some diseases, but how these processes progress and regulated in silicosis, remains limited. Detailed study of silica induced pulmonary fibrosis in mouse model, its progression and severity may be helpful in designing future therapeutic strategies. MethodsIn present study, mice model of silicosis has been developed after repeated silica exposures which may closely resemble clinical symptoms of silicosis in human. In addition to efficiently mimicking the acute/chronic transformation processes of silicosis, this is practical and efficient in terms of time and output, which avoids mechanical injury to the upper respiratory tract due to surgical interventions. Sonicated sterile silica suspension (120 mg/kg) was administered through intranasal route thrice a week at regular intervals (21, 28 and 35 days). ResultsPresence of minute to larger silicotic nodules in H&E-stained lung sections were observed in all silica induced model groups. Enhanced ECM deposition was noted in MT stained lung sections of silica exposure groups as compared to control which were confirmed by significantly higher MMP9 expression levels and hydroxyproline content in silica 35 days group. Increase in Reactive oxygen species (ROS), inflammatory cell recruitment mainly, neutrophils and macrophage were observed in all three silica exposure groups. Transmission electron microscopic analysis has confirmed presence of many aberrant shaped mitochondria (swollen, round shape) in 35 days model where autophagosomes were minimum. Western blot analysis of mitophagy and autophagy markers such as Pink1, Parkin, Cytochrome c, SQSTM1/p62, the ratio of light chain LC3B II/LC3B I was found higher in 21 and 28 days which were significantly reduced in 35 days silica model. ConclusionsHigher MMP9 activity and MMP9 /TIMP1 ratio demonstrate excessive extracellular matrix damage and deposition in 35 days model. Significantly reduced expressions of autophagy and mitophagy markers have also confirmed progression in fibrosis severity and its association with repeated silica exposures in 35 days model group.

Cardiac Complications and COVID-19: A Review of Life-threatening Co-morbidities.

The novel 2019 coronavirus disease (COVID-19) was first reported in the last days of December 2019 in Wuhan, China. The presence of certain co-morbidities, including cardiovascular diseases (CVDs), are the basis for worse outcomes in patients with COVID-19. Relevant English-language literature was searched and retrieved from the Google Scholar search engine and PubMed database up to 2023 using COVID-19, SARS-CoV-2, Heart failure, Myocardial infarction, and Arrhythmia and Cardiac complication as keywords. Increased hemodynamic load, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, and excessive or insufficient extracellular matrix proliferation are associated with heart failure (HF) in COVID-19 patients. Inflammatory reaction due to the excessive release of inflammatory cytokines, leads to myocardial infarction (MI) in these patients. The virus can induce heart arrhythmia through cardiac complications, hypoxia, decreased heart hemodynamics, and remarkable inflammatory markers. Moreover, studies have linked cardiac complications in COVID-19 with poor outcomes, extended hospitalization time, and increased mortality rate. Patients with COVID-19 and CVDs are at higher mortality risk and they should be given high priority when receiving the treatment and intensive care during hospitalization.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond.

After half a century of evidence suggesting the existence of mineralocorticoid receptors (MR) in the vasculature, the advent of technology to specifically knockout the MR from smooth muscle cells (SMCs) in mice has elucidated contributions of SMC-MR to cardiovascular function and disease, independent of the kidney. This review summarizes the latest understanding of the molecular mechanisms by which SMC-MR contributes to (1) regulation of vasomotor function and blood pressure to contribute to systemic and pulmonary hypertension; (2) vascular remodeling in response to hypertension, vascular injury, obesity, and aging, and the impact on vascular calcification; and (3) cardiovascular pathologies including aortic aneurysm, heart valve dysfunction, and heart failure. Data are reviewed from in vitro studies using SMCs and in vivo findings from SMC-specific MR-knockout mice that implicate target genes and signaling pathways downstream of SMC-MR. By regulating expression of the L-type calcium channel subunit Cav1.2 and angiotensin II type-1 receptor, SMC-MR contributes to myogenic tone and vasoconstriction, thereby contributing to systemic blood pressure. MR activation also promotes SMC proliferation, migration, production and degradation of extracellular matrix, and osteogenic differentiation by regulating target genes including connective tissue growth factor, osteopontin, bone morphogenetic protein 2, galectin-3, and matrix metallopeptidase-2. By these mechanisms, SMC-MR promotes disease progression in models of aging-associated vascular stiffness, vascular calcification, mitral and aortic valve disease, pulmonary hypertension, and heart failure. While rarely tested, when sexes were compared, the mechanisms of SMC-MR-mediated disease were sexually dimorphic. These advances support targeting SMC-MR-mediated mechanisms to prevent and treat diverse cardiovascular disorders.

Mechanistic Roles of Different Varieties of Honey on Wound Healing: Recent Update

Background Honey has been used for centuries for its medicinal benefits, where topical treatments in the folklore literature reported its beneficial role in treating different types of wounds. Despite its immense use in wound care, honey’s exact mechanism remains unclear. Purpose The present study aimed to explore and abridge the gap between honey and its molecular wound healing mechanism. Methodology An extensive literature study has been performed where these activities can be explained due to phenolic compounds, nitric oxide, non-peroxide factors, low pH, high osmolarity, and hydrogen peroxide in honey. Besides that, honey also contains carbohydrates, proteins, amino acids, lipids, minerals, and vitamins, contributing to the wound healing potential to some extent. However, these metabolites and constituents differ among different honey varieties due to the distinct nutritional requirements of different species of bees and their collection of nectar from varied sources containing different natural actives. Results The revival of honey-based wound care research has identified a few probable mechanistic pathways of honey primarily due to its anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory potentials. It also promotes angiogenesis, facilitates reepithelialization, stimulates proliferation of extracellular matrix, reduces neutrophil formation, modulates production of TNF-α, IL-1β, and IL-6, and prevents secondary infection at the wound site. Conclusion The varieties of honey vary in their qualities, phenolic compounds, and safety for human use. A few of these are currently clinically employed for wound dressings. Moreover, honey can be effective for managing complicated and chronic wounds; more extensive molecular research and safety profiling would be necessary.

Cellular behavior and extracellular matrix turnover in bovine annulus fibrosus cells under hydrostatic pressure and deviatoric strain.

Intervertebral disc herniation is a common spinal disorder that is often treated with discectomy when conservative measures fail. To devise therapeutic strategies for tears in the annulus fibrosus (AF), the regenerative capability of AF cells under spinal loading needs to be addressed. We hypothesized that the compressive loading associated with deformation in AF cells reduces synthetic and degradative activities in extracellular matrix and cell proliferation. We evaluated expression of key matrix molecules and cell proliferation by RT-PCR and immunohistochemistry by inner and outer bovine AF cells incubated under hydrostatic pressure (HP), arc-bending strain (Strain), and combined HP and Strain (HP/Strain) mimicking spinal loading. Inner AF cells showed significantly increased levels of aggrecan core protein, chondroitin sulfate N-acetylgalactosaminyltransferase-1, and tissue inhibitor of metalloproteinases-2 by 6 days under HP (p < 0.05), with a tendency toward increased matrix metalloproteinase-13. Outer AF cells demonstrated a significant decline in collagen type-2 under Strain and HP/Strain (p < 0.05) and a tendency toward suppression of collagen type-1 and elastin expression compared to HP and unloaded control. On the other hand, proliferating cell nucleus antigen increased significantly under Strain and HP/Strain in inner AF and declined under unloaded and HP in outer AF (p < 0.05). Immunohistology findings supported reductions in gene expressions of matrix molecules. Thus, changes in HP/Strain in AF appear to diminish synthetic and degradative activities while increasing cell proliferation. To promote regeneration, continuous overloading should be avoided, as it converts the synthetic activity to a state in which tissue repair is limited.

TSP-1 increases autophagy level in cartilage by upregulating HSP27 which delays progression of osteoarthritis

This study aimed to determine whether Thrombospondin-1 (TSP-1) can be used as a biomarker to diagnose early osteoarthritis (OA) and whether it has a chondroprotective effect against OA. We examined TSP-1 expression in cartilage, synovial fluid, and serum at different time points after anterior cruciate ligament transection (ACLT) surgery in rats. Subsequently, TSP-1 was overexpressed or silenced to detect its effects on extracellular matrix (ECM) homeostasis, autophagy level, proliferation and apoptosis in chondrocytes. Adenovirus encoding TSP-1 was injected into the knee joints of ACLT rats to test its effect against OA. Combined with proteomic analysis, the molecular mechanism of TSP-1 in cartilage degeneration was explored. Intra-articular injection of an adenovirus carrying the TSP-1 sequence showed chondroprotective effects against OA. Moreover, TSP-1 expression decreases with OA progression and can effectively promote cartilage proliferation, inhibit apoptosis, and helps to sustain the balance between ECM anabolism and catabolism. Overexpression of TSP-1 also can increase autophagy by upregulating Heat Shock Protein 27 (HSP27, hspb1), thereby enhancing its effect as a stimulator of autophagy. TSP-1 is a hopeful strategy for OA treatment.

Harnessing the Regenerative Potential of Fetal Mesenchymal Stem Cells and Endothelial Colony‐Forming Cells in the Biofabrication of Tissue‐Engineered Vascular Grafts (TEVGs)

Tissue engineering is a promising approach for the production of small‐diameter vascular grafts; however, there are limited data directly comparing the suitability of applicable cell types for vessel biofabrication. Here, we investigated the potential of adult smooth muscle cells (SMCs), placental mesenchymal stem cells (MSCs), placental endothelial colony‐forming cells (ECFCs), and a combination of MSCs and ECFCs on highly porous biocompatible poly(ɛ‐caprolactone) (PCL) scaffolds produced via melt electrowriting (MEW) for the biofabrication of tissue‐engineered vascular grafts (TEVGs). Cellular attachment, proliferation, and deposition of essential extracellular matrix (ECM) components were analysed in vitro over four weeks. TEVGs cultured with MSCs accumulated the highest levels of collagenous components within a dense ECM, while SMCs and the coculture were more sparsely populated, ascertained via histological and immunofluorescence imaging, and biochemical assessment. Scanning electron microscopy (SEM) enabled visualisation of morphological differences in cell attachment and growth, with MSCs and SMCs infiltrating and covering scaffolds completely within the 28‐day culture period. Coverage and matrix deposition by ECFCs was limited. However, ECFCs lined the ECM formed by MSCs in coculture, visualised via immunostaining. Thus, of cells investigated, placental MSCs were identified as the preferred cell source for the fabrication of tissue‐engineered constructs, exhibiting extensive population of porous polymer scaffolds and production of ECM components; with the inclusion of ECFCs for luminal endothelialisation, an encouraging outcome warranting further consideration in future studies. In combination, these findings represent a substantial step toward the development of the next generation of small‐diameter vascular grafts in the management of cardiovascular disease.

Regulation effect of the intestinal flora and intervention strategies targeting the intestinal flora in alleviation of pulmonary fibrosis development.

Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.

Interleukin-6 gene polymorphism (rs1800796) in patient with diabetic nephropathy among Balinese

Background: Diabetic Nephropathy (DN) is the most common complication of diabetes mellitus. Interleukin 6 (IL-6) known as pro-inflammatory cytokine increases extracellular matrix expression and proliferation in DN progression. One single nucleotide polymorphism (SNP) of the Interleukin (IL)-6 gene, rs1800796 play a role in the progression of DN among Asian. Objective: This research seeks to investigate the correlation between IL-6 gene polymorphism (rs1800796) and diabetic nephropathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) among the Balinese population.Methods: This research employed an observational approach through a case-control design involving a total of 60 subjects for each group selected by a simple random sampling method. The occurrence of the rs1800796 polymorphism was identified through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele distribution acquired in this study were assessed using the chi-square (χ2) test and Hardy-Weinberg equilibrium law.Results: There were no significant differences identified in the occurrence of (DN) based on the genotype or allele distribution of the IL-6 gene rs1800796. Genotype CG-GG had a higher risk of becoming DN with Odd ratio 1.230, but not statistically significant (p=0.577). Allele G with OR 1.198 (p=0.502) was not significant in causing DN. Conclusion: No significant association was identified between IL-6 polymorphism (rs1800796) and diabetic nephropathy in Balinese individuals with type 2 diabetes mellitus. The lack of association could be due to the presence of other haplotypic connections or might require a larger sample size for conclusive results.

ALA-PDT promotes the death and contractile capacity of hypertrophic scar fibroblasts through inhibiting the TGF-β1/Smad2/3/4 signaling pathway

BackgroundHypertrophic scars, an abnormal wound-healing response to burn injuries, are characterized by massive fibroblast proliferation and excessive deposition of extracellular matrix and collagen. 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is a promising therapy for hypertrophic scar, details of the mechanisms remain to be elucidated. In this study, we aimed to investigate the molecular mechanisms involved in ALA-PDT against hypertrophic scar fibroblasts. MethodsThe morphologies of hypertrophic scar fibroblasts (HSFs) treated with ALA-PDT were observed under a light microscopy. The viability of HSFs was detected using the CCK-8 assay. HSFs-populated collagen gel contraction assays were conducted to examine the fibroblast contractility and the cytotoxicity of HSFs in 3D collagen tissues were observed using confocal microscopy. The effect of ALA-PDT on TGF-β1/Smad2/3/4 signaling pathway activation and effector gene expression were verified by immunoprecipitation, western blot and real-time quantitative PCR analysis. ResultsWe observed significant changes in cell morphology after ALA-PDT treatment of HSFs. As ALA concentration and light dose increased, the viability of HSFs significantly decreased. ALA-PDT can significantly alleviate the contractile capacity and promote the death of HSFs induced by TGF-β1 treatment in a three-dimensional collagen culture model. TGF-β1 treatment of HSFs can significantly induce phosphorylation of Smad2/3 (p-Smad2/3) in whole cells, as well as p-Smad2/3 and Smad4 proteins into the nucleus and increase the mRNA levels of collagen 1/3 and α-SMA. ALA-PDT hampers the TGF-β1-Smad2/3/4 signaling pathway activation by inducing K48-linked ubiquitination and degradation of Smad4. ConclusionsOur results provide evidence that ALA-PDT can inhibit fibroblast contraction and promote cell death by inhibiting the activation of the TGF-β1 signaling pathway that mediates hypertrophic scar formation, which may be the basis for the efficacy of ALA-PDT in the treatment of hypertrophic scars.

The Role of Periodontal Ligament Remodeling on Orthodontic Tooth Movement

The periodontal ligament is a connective tissue located between the cementum that covers the roots of the tooth and alveolar bone, which is composed of large amounts of fibers, cells, and blood vessels. Orthodontic tooth movements are obtained through periodontal ligament remodeling and alveolar bone in response to orthodontic forces. When the orthodontic force is applied to the teeth, an injury will occur in the periodontal ligament, and the pressure and tension side in the periodontal ligament is formed. Furthermore, vasoconstriction occurs in blood vessels and hypoxia in the periodontal ligament, triggering inflammation, angiogenesis, cell proliferation, degradation, and synthesis of extracellular matrix, bone resorption, and alveolar bone deposition. The purpose of this article is to study the mechanism of periodontal ligament remodeling on orthodontic tooth movement to obtain optimal tooth movements.

Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs.

Background Idiopathic pulmonary fibrosis (IPF) is identified as a chronic, progressive lung disease, predominantly marked by enhanced fibroblast proliferation and excessive deposition of extracellular matrix. The intricate interactions between diverse molecular pathways in fibroblasts play a crucial role in driving the pathogenesis of IPF. Methods This research is focused on elucidating the roles of FOXO3a, a transcription factor, and USP18, a ubiquitin-specific protease, in modulating fibroblast functionality in the context of IPF. FOXO3a is well-known for its regulatory effects on cellular responses, including apoptosis and oxidative stress, while USP18 is generally associated with protein deubiquitination. Results Our findings highlight that FOXO3a acts as a critical regulator in controlling fibroblast activation and differentiation, illustrating its vital role in the pathology of IPF. Conversely, USP18 seems to promote fibroblast proliferation and imparts resistance to apoptosis, thereby contributing to the exacerbation of fibrotic processes. The synergistic dysregulation of both FOXO3a and USP18 in fibroblasts was found to significantly contribute to the fibrotic alterations characteristic of IPF. Conclusion Deciphering the complex molecular interactions between FOXO3a and USP18 in fibroblasts provides a deeper understanding of IPF pathogenesis and unveils novel therapeutic avenues, offering a promising potential for not just halting but potentially reversing the progression of this debilitating disease.

Transcriptome sequencing for identification of the genes associated with restenosis of venous grafts in rabbits

To identify the genes associated with venous graft restenosis in rabbits using transcriptome sequencing. Forty New Zealand rabbits were randomly divided into experimental group and control group, and in the experimental group, the left external jugular veins of the rabbits were engrafted to the left common carotid artery with continuous running suture; the rabbits in the control group received no operation. At 2 and 4 weeks after the operation, 10 rabbits from each group were euthanized and the venous grafts (in experimental group) or left external jugular vein (in control group) were harvested for measurement of the intima-media thickness using HE staining. RNA high-throughput sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs) between the venous grafts and the control veins, and the biological functions of the DEGs were analyzed using GO and KEEG databases. In the experimental group, intima-media thickening with increased extracellular matrix and vascular smooth muscle cell proliferation occurred in the venous grafts at 2 weeks and aggravated at 4 weeks after the operation. RNA high-throughput sequencing identified 1583 up-regulated genes and 608 down-regulated genes in the venous grafts in the experimental group, and GO and KEGG analysis of the DEGs pinpointed 10 hub genes, namely CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK. CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK are probably the key genes associated with vein graft restenosis in rabbits.