Excessive Accumulation Of Collagen Research Articles

Baicalin: a potential therapeutic agent for acute kidney injury and renal fibrosis

Acute kidney injury (AKI) is a common critical clinical disease that is linked to significant morbidity, recurrence, and mortality. It is characterized by a fast and prolonged loss in renal function arising from numerous etiologies and pathogenic pathways. Renal fibrosis, defined as the excessive accumulation of collagen and proliferation of fibroblasts within renal tissues, contributes to the structural damage and functional decline of the kidneys, playing a pivotal role in the advancement of Chronic Kidney Disease (CKD). Until now, while continuous renal replacement therapy (CRRT) has been utilized in the management of severe AKI, there remains a dearth of effective targeted therapies for AKI stemming from diverse etiologies. Similarly, the identification of specific biomarkers and pharmacological targets for the treatment of renal fibrosis remains a challenge. Baicalin, a naturally occurring compound classified within the flavonoid group and commonly found in the Chinese herb Scutellaria baicalensis, has shown a range of pharmacological characteristics, such as antioxidant, anti-inflammatory, antifibrotic, antitumor and antiviral effects, as evidenced by research studies. Research shows that Baicalin has potential in treating kidney diseases like AKI and renal fibrosis. This review aims to summarize Baicalin’s progress in these areas, including its molecular mechanism, application in treatment, and absorption, distribution, metabolism, and excretion. Baicalin’s therapeutic effects are achieved through various pathways, including antioxidant, anti-inflammatory, antifibrosis, and regulation of apoptosis and cell proliferation. Besides, we also hope this review may give some enlightenment for treating AKI and renal fibrosis in clinical practice.

Green tea and green coffee for cardiac fibrosis treatment: A review

Cardiac fibrosis, marked by excessive collagen accumulation and tissue remodelling, is a key factor in heart dysfunction across various cardiovascular conditions. With limited effective treatments currently available, there is growing interest in exploring natural therapies like green tea and green coffee for their potential antifibrotic properties. Both beverages contain bioactive compounds, such as catechins and caffeic acid, known for their antioxidant, anti-inflammatory, and cardioprotective effects. Green tea has been shown to reduce oxidative stress, lower fibrosis-related markers, and limit collagen deposition in heart tissue. Similarly, caffeic acid from coffee has demonstrated the ability to block fibrosis-driving pathways, such as TGF-β1 signalling, and support cardiac recovery following myocardial infarction. Moreover, the combined use of green tea and decaffeinated green coffee has been found to improve metabolic health by influencing cardiac insulin pathways, which could help mitigate fibrosis in metabolic syndrome models. This review consolidates recent evidence on the mechanisms and benefits of green tea and green coffee in addressing cardiac fibrosis. It highlights their potential as accessible, non-invasive treatment options and underscores the need for further studies to confirm their therapeutic applications in clinical settings.

Quercetin-Loaded Melanin Nanoparticles Decorated with Collagenase Mediates Synergistic Immunomodulation and Restores Extracellular Matrix Homeostasis in Liver Fibrosis.

Liver fibrosis is a chronic disease that lacks effective drug treatment. Chronic damage and inflammation lead to the formation of collagen and fibrous scars. However, the excessive accumulation of collagen I significantly hinders the delivery of drugs into liver tissue. Therefore, this study developed a quercetin-loaded melanin nanoparticle codecorated collagenase (MNP-QUE-COL) for the treatment of liver fibrosis. These results showed that MNP-QUE-COL degraded excessive collagen I, thereby efficiently delivering melanin and quercetin into the liver tissue. MNP-QUE-COL exhibited optimal PA/MRI dual-mode imaging ability. In addition, the synergistic anti-inflammatory and reactive oxygen species scavenging function of quercetin and melanin was achieved by regulation of M1-M2 macrophage polarization and inhibition of pro-inflammatory cytokine release, reshaping the imbalanced extracellular interstitial inflammatory environment. The results of this research suggest that MNP-QUE-COL is a safe and efficient therapeutic nanoplatform for liver fibrosis, showing promise as a potential therapeutic strategy for liver fibrosis and associated diseases.

Berberine attenuates ECM accumulation and the progression of acute liver failure through inhibition of NLRP3 inflammasome signalling

Acute liver failure (ALF) is a life-threatening disease, characterized by upregulated extracellular matrix deposition and inflammatory signalling, with no effective treatment options and targets. The present study was designed to investigate the preventive and therapeutic effects of berberine (BBR) and its underlying mechanism in thioacetamide (TAA)-induced ALF. Male SD rats were administered with TAA 300 mg/kg, i.p., thrice to induce ALF and pre- or post-treated with BBR. To decipher the effects of BBR LFT markers, histopathological analysis of key fibrotic and inflammatory proteins was performed. In addition, the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were assessed by ELISA. Our work showed TAA-induced ALF animals were associated with increased ALT, AST, bilirubin (LFT markers) and histopathological alterations with profuse infiltration of inflammatory cells in the liver tissue. Treatment with BBR has significantly inhibited LFT markers and histological alterations triggered by TAA. In addition, TAA animals demonstrated increased collagen accumulation and upregulated expression of TGF-β1, vimentin, and α-SMA compared to control. The excessive accumulation of collagen, TGF-β1, vimentin, and α-SMA were significantly modulated with BBR treatment. Further, the fluorescence intensity of ROS an activator of NLRP3 including the NLRP3 inflammasome, and its downstream signalling ASC, cleaved IL-1β, and other pro-inflammatory cytokines like TNF-α and IL-6 stimulated by TAA were attenuated by BBR treatment. The current work indicated that BBR significantly ameliorated TAA-induced ALF by inhibiting the extracellular matrix accumulation associated with the NLRP3/IL-1β signalling pathway and could be a viable therapeutic option to treat ALF and other fibroinflammatory diseases.

Signaling pathways that activate hepatic stellate cells during liver fibrosis.

Liver fibrosis is a complex process driven by various factors and is a key feature of chronic liver diseases. Its essence is liver tissue remodeling caused by excessive accumulation of collagen and other extracellular matrix. Activation of hepatic stellate cells (HSCs), which are responsible for collagen production, plays a crucial role in promoting the progression of liver fibrosis. Abnormal expression of signaling pathways, such as the TGF-β/Smads pathway, contributes to HSCs activation. Recent studies have shed light on these pathways, providing valuable insights into the development of liver fibrosis. Here, we will review six signaling pathways such as TGF-β/Smads that have been studied more in recent years.

Human amniotic membrane modulates collagen production and deposition in vitro

Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation of excess collagen at the site of repair which can compromise the tissue architecture and severely impede the function of the affected tissue. Few prophylactic treatments exist to counteract this process; however, the use of amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed to identify the underlying mechanism of action by utilizing relevant models that accurately represent the pathophysiology of the disease state. This study employed a pro-fibrotic in vitro system using TGFβ1 stimulation and macromolecular crowding techniques to evaluate the mechanism by which amniotic membrane allografts regulate collagen biosynthesis and deposition. Following treatment with dehydrated human amnion chorion membrane (DHACM), subsequent RNA sequencing and functional enrichment with Reactome pathway analysis indicated that amniotic membranes are indeed capable of regulating genes associated with the composition and function of the extracellular matrix. Furthermore, macromolecular crowding was used in vitro to expand the evaluation to include both the effects of DHACM and a lyophilized human amnion/chorion membrane (LHACM). DHACM and LHACM regulate the TGFβ pathway and myofibroblast differentiation. Additionally, both DHACM and LHACM modulate the production, secretion, and deposition of collagen type I, a primary target for pathological fibrosis. These observations support the hypothesis that amniotic membranes may interrupt pathological fibrosis by regulating collagen biosynthesis and associated pathways.

Human Umbilical Cord Mesenchymal Stem Cells Combined with Dehydroepiandrosterone Inhibits Inflammation-Induced Uterine Aging in Mice.

With the postponement of the reproductive age of women, the difficulty of embryo implantation caused by uterine aging has become a key factor restricting fertility. However, there are few studies on protective interventions for naturally aging uteri. Although many factors cause uterine aging, such as oxidative stress (OS), inflammation, and fibrosis, their impact on uterine function manifests as reduced endometrial receptivity. This study aimed to use a combination of human umbilical cord mesenchymal stem cells (hUC-MSCs) and dehydroepiandrosterone (DHEA) to delay uterine aging. The results showed that the combined treatment of hUC-MSCs + DHEA increased the number of uterine glandular bodies and the thickness of the endometrium while inhibiting the senescence of endometrial epithelial cells. This combined treatment alleviates the expression of OS (reactive oxygen species, superoxide dismutase, and GSH-PX) and proinflammatory factors (interleukin [IL]-1, IL6, IL-18, and tumor necrosis factor-α) in the uterus, delaying the aging process. The combined treatment of hUC-MSCs + DHEA alleviated the abnormal hormone response of the endometrium, inhibited excessive accumulation and fibrosis of uterine collagen, and upregulated uterine estrogen and progesterone receptors through the PI3K/AKT/mTOR pathway. This study suggests that uterine aging can be delayed through hUC-MSCs + DHEA combination therapy, providing a new treatment method for uterine aging.

SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY.

Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro . RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.

Abstract 6383: Targeting radiation-induced fibrosis: Exploring promising therapeutic avenues and innovative assessment methods

Abstract Introduction: Radiation therapy is a vital cancer treatment for nearly 50% of patients, yet it poses a significant challenge in the form of radiation-induced fibrosis (RF). RF affects about 60% of those undergoing radiation, leading to painful scarring from excessive collagen accumulation. In head and neck cancer patients, as an example, RF reduces tissue flexibility, causing limited neck mobility and impaired swallowing. Furthermore, approximately 30% of patients also face disease recurrence post-radiation, with RF increasing surgical complications. Our laboratory previously identified the role of reduced fatty acid oxidation in RF (Zhao et al; Nat Metab;1(1):147 2019), offering a promising avenue for future drug development. We described the potential therapeutic benefit of caffeic acid phenethyl ester (CAPE) in countering pro-fibrotic metabolic changes. Our current objective is to develop more effective lead compounds to mitigate RF. Methods: Collagen expression, utilized as a surrogate marker for fibrosis, was quantified using ELISA, Western blot analysis, and RT-qPCR. Metabolic changes were assessed by examining the expression levels of PPARG and CD36. CAPE-like analogs were derived from an in-house collection, a commercially available library, and structure-activity relationship (SAR) analyses. In vivo, RF was induced in the hindlimbs of mice through exposure to 40 Gy, followed by weekly X-ray evaluations of hindlimb angles for 16 weeks. During X-ray assessments, both hindlimbs were subjected to a 5 g weight to enable measurement of the joint angle between the femur and tibia (wherein higher acute angles were a measure of worsening fibrosis). Skin samples from irradiated and unirradiated limbs were collected for the evaluation of collagen deposition, utilizing Picro Sirius staining followed by polarized microscopy. Results: Amongst 200 newly synthesized analogs, approximately one-third successfully reduced collagen secretion in human primary dermal fibroblasts. The most promising compounds exhibited a half-maximum inhibition concentration (IC50) for collagen secretion from 1 to 5µM. They also decreased intracellular collagen production and gene expression, associated with upregulation of PPARG and CD36 transcripts. The joint angle measurements in vivo revealed three distinct phases in the development of dermal fibrosis: 1) inflammatory; 2) recovery; and 3) fibrotic phases. Conclusions: We have successfully synthesized novel and potent analogs of CAPE which were able to reduce secretion of collagen. Furthermore, a novel method for the in vivo assessment of fibrosis was also developed. This innovative approach will facilitate the detailed assessments of future compounds capable of reducing collagen deposition in vivo, thereby providing an innovative avenue to mitigate one of the most pressing late normal tissue toxicities of radiation therapy. Citation Format: Pierre-Antoine Bissey, Leonardo Massignan, Ross Mancini, Wei Shi, Justin Williams, Mark Reed, Kenneth W. Yip, Fei-Fei Liu. Targeting radiation-induced fibrosis: Exploring promising therapeutic avenues and innovative assessment methods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6383.

The Protective Effects of Vitamin B Complex on Diclofenac Sodium-Induced Nephrotoxicity: The Role of NOX4/RhoA/ROCK.

Diclofenac sodium (DIC) is a widely used non-steroidal anti-inflammatory drug. Unfortunately, its prolonged use is associated with nephrotoxicity due to oxidative stress, inflammation, and fibrosis. We aimed to investigate the nephroprotective effects of vitamin B complex (B1, B6, B12) against DIC-induced nephrotoxicity and its impact on NOX4/RhoA/ROCK, a pathway that plays a vital role in renal pathophysiology. Thirty-two Wistar rats were divided into four groups: (1) normal control; (2) vitamin B complex (16 mg/kg B1, 16 mg/kg B6, 0.16 mg/kg B12, intraperitoneal); (3) DIC (10 mg/kg, intramuscular); and (4) DIC plus vitamin B complex group. After 14 days, the following were assayed: serum renal biomarkers (creatinine, blood urea nitrogen, kidney injury molecule-1), oxidative stress, inflammatory (tumor necrosis factor-α, interleukin-6), and fibrotic (transforming growth factor-β) markers as well as the protein levels of NOX4, RhoA, and ROCK. Structural changes, inflammatory cell infiltration, and fibrosis were detected using hematoxylin and eosin and Masson trichrome stains. Compared to DIC, vitamin B complex significantly decreased the renal function biomarkers, markers of oxidative stress and inflammation, and fibrotic cytokines. Glomerular and tubular damage, inflammatory infiltration, and excessive collagen accumulation were also reduced. Protein levels of NOX4, RhoA, and ROCK were significantly elevated by DIC, and this elevation was ameliorated by vitamin B complex. In conclusion, vitamin B complex administration could be a renoprotective approach during treatment with DIC via, at least in part, suppressing the NOX4/RhoA/ROCK pathway.

Accelerated scarless wound healing by dynamical regulation of angiogenesis and inflammation with immobilized asiaticoside and magnesium ions in silk nanofiber hydrogels.

It remains a challenge to effectively regulate the complicated microenvironment during the wound healing process. The optimization of synergistic action of angiogenesis and inflammation is considered critical for quicker scarless wound regeneration. Here, the silk nanofiber (SNF) acts as a multifunctional carrier to load hydrophobic asiaticoside (AC) and hydrophilic Mg2+, and also serves as an element to assemble injectable hydrogels, forming a bioactive matrix with improved angiogenic and anti-inflammatory capacities (SNF-AC-Mg). Mg2+ and AC distributed homogeneously inside the silk nanofiber hydrogels without compromising the mechanical performance. Both Mg2+ and AC released slowly to continuously tune both angiogenic and inflammatory behaviors. The hydrogels exhibited good biocompatibility, inflammation inhibition, and pro-angiogenic properties in vitro, suggesting the synergistic bioactivity of AC and Mg2+. In vivo analysis revealed that the synergistic action of AC and Mg2+ resulted in better M2-type polarization of macrophages and angiogenesis during the inflammatory phase, while effectively achieving the inhibition of excessive accumulation of collagen and scar formation during the remodeling phases. The quicker scarless regeneration of the defects treated with SNF-AC-Mg implies the priority of SNFs in designing bioactive niches with complicated cues, which will favor the functional recovery of different tissues in the future.

Endometrial organoids: a reservoir of functional mitochondria for uterine repair.

Background: Asherman's syndrome (AS) is a dreadful gynecological disorder of the uterus characterized by intrauterine adhesion with severe fibrotic lesions, resulting in a damaged basalis layer with infertility. Despite extensive research on overcoming AS, evidence-based effective and reproducible treatments to improve the structural and functional morphology of the AS endometrium have not been established. Methods: Endometrial organoids generated from human or mouse endometrial tissues were transplanted into the uterine cavity of a murine model of AS to evaluate their transplantable feasibility to improve the AS uterine environment. The successful engraftment of organoid was confirmed by detection of human mitochondria and cytosol (for human endometrial organoid) or enhanced green fluorescent protein signals (for mouse endometrial organoid) in the recipient endometrium. The therapeutic effects mediated by organoid transplantation were examined by the measurements of fibrotic lesions, endometrial receptivity and angiogenesis, and fertility assessment by recording the number of implantation sites and weighing the fetuses and placenta. To explore the cellular and molecular mechanisms underlying the recovery of AS endometrium, we evaluated the status of mitochondrial movement and biogenetics in organoid transplanted endometrium. Results: Successfully engrafted endometrial organoids with similar morphological and molecular features to the parental tissues dramatically repaired the AS-induced damaged endometrium, significantly reducing fibrotic lesions and increasing fertility outcomes in mice. Moreover, dysfunctional mitochondria in damaged tissues, which we propose might be a key cellular feature of the AS endometrium, was fully recovered by functional mitochondria transferred from engrafted endometrial organoids. Endometrial organoid-originating mitochondria restored excessive collagen accumulation in fibrotic lesions and shifted uterine metabolic environment to levels observed in the normal endometrium. Conclusions: Our findings suggest that endometrial organoid-originating mitochondria might be key players to mediate uterine repair resulting in fertility enhancement by recovering abrogated metabolic circumstance of the endometrium with AS. Further studies addressing the clinical applicability of endometrial organoids may aid in identifying new therapeutic strategies for infertility in patients with AS.

3D printing of Rg3-loaded hydrogel scaffolds: anti-inflammatory and scar-formation related collagen inhibitory effects for scar-free wound healing.

During the process of wound healing, the stimulation of inflammatory factors often leads to abnormal proliferation of blood vessels and collagen, ultimately resulting in scar formation. To address this challenge, we fabricate a novel dermal extracellular matrix (DECM) hydrogel scaffold loaded with ginsenoside Rg3 (Rg3) using 3D printing technology. Mesoporous silica nanoparticles (MSNs) are introduced into the system to encase the Rg3 to control its release rate and enhance its bioavailability. We systematically evaluate the biological, physicochemical, and wound healing properties of this scaffold. In vitro studies demonstrate that the hydrogel exhibits excellent biocompatibility and solid-like rheological properties, ensuring its successful printing. In vivo studies reveal that the composite hydrogel scaffolds effectively accelerate wound healing and achieve scar-free wound healing within three weeks. Histological and immunohistochemical (IHC) analyses show that the composite hydrogel scaffolds reduce the inflammatory response and inhibit excessive collagen accumulation. These combined effects underscore the potential of our approach in effectively inhibiting scar formation.

Matrix metalloproteinases inhibition reveals the association between inflammation, collagen accumulation and intestinal translocation of Schistosoma mansoni eggs in vivo

Schistosomiasis mansoni is a parasitic infection that causes enterohepatic morbidity associated with severe granulomatous inflammation triggered by parasite eggs. In this disease, granulomatous inflammation leads to intestinal erosion and environmental excretion of S. mansoni eggs from feces, an essential process for propagating the parasite and infecting host organisms. Metalloproteinases (MMP) are involved in S. mansoni-induced hepatic granulomatous inflammation and fibrosis. However, the relationship between MMP and collagen accumulation with the intestinal excretion of parasite eggs remains unclear. Thus, the present study investigated whether MMP inhibition is capable of modulating granulomatous inflammation, collagen accumulation and mechanical resistance to the point of influencing the dynamics between intestinal retention and excretion of S. mansoni eggs in infected mice. Our findings indicated that doxycycline (a potent MMP inhibitor) aggravates intestinal inflammation and subverts collagen dynamics in schistosomiasis. By attenuating MMP-2 and MMP-9 activity, this drug is capable of enhancing fibrosis and mechanical resistance of the intestinal wall, hindering S. mansoni eggs translocation. Although collagen content was not correlated with MMP activity, intestinal retention and fecal excretion of parasite eggs in untreated mice; these correlations were observed for doxycycline-treated animals. Thus, our study provides evidence that doxycycline is able to attenuate fecal elimination of S. mansoni eggs by inhibiting MMP-2 and MMP-9 activity, events potentially associated with excessive collagen accumulation, which increases intestinal mechanical resistance and hinders eggs translocation through the intestinal wall. Variations in intestinal collagen dynamics are relevant since they may represent changes in the environmental dispersion of S. mansoni eggs, bringing repercussions for schistosomiasis propagation.

Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials

BackgroundThe liver was identified as a primary target organ for the chemo-radiological effects of uranyl acetate (UA). Although the anti-oxidant and anti-apoptotic properties of gallic acid (GA) make it a promising phytochemical to resist its hazards, there is no available data in this area of research.MethodsTo address this issue, eighteen rats were randomly and equally divided into three groups. One group was received carboxymethyl cellulose (vehicle of GA) and kept as a control. The UA group was injected intraperitoneally with UA at a single dose of 5 mg/kg body weight. The third group (GA + UA group) was treated with GA orally at a dose of 100 mg/kg body weight for 14 days before UA exposure. UA was injected on the 15th day of the experiment in either the UA group or the GA + UA group. The biochemical, histological, and immunohistochemical findings in the GA + UA group were compared to both control and UA groups.ResultsThe results showed that UA exposure led to a range of adverse effects. These included elevated plasma levels of aspartate aminotransferase, lactate dehydrogenase, total protein, globulin, glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein and decreased plasma levels of high-density lipoprotein cholesterol. The exposure also disrupted the redox balance, evident through decreased plasma total antioxidant capacity and hepatic nitric oxide, superoxide dismutase, reduced glutathione, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase and increased hepatic oxidized glutathione and malondialdehyde. Plasma levels of albumin and alanine aminotransferase did not significantly change in all groups. Histopathological analysis revealed damage to liver tissue, characterized by deteriorations in tissue structure, excessive collagen accumulation, and depletion of glycogen. Furthermore, UA exposure up-regulated the immuno-expression of cleaved caspase-3 and down-regulated the immuno-expression of nuclear factor-erythroid-2-related factor 2 in hepatic tissues, indicating an induction of apoptosis and oxidative stress response. However, the pre-treatment with GA proved to be effective in mitigating these negative effects induced by UA exposure, except for the disturbances in the lipid profile.ConclusionsThe study suggests that GA has the potential to act as a protective agent against the adverse effects of UA exposure on the liver. Its ability to restore redox balance and inhibit apoptosis makes it a promising candidate for countering the harmful effects of chemo-radiological agents such as UA.

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway

Context Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear. Objective These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI. Materials and methods Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1β (IL-1β) and IL-18 were evaluated. Results Punicalagin had binding activities with NLRP3 (Vina score, −5.8), caspase-1 (Vina score, −6.7), and GSDMD (Vina score, −6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p < 0.01), and inhibit cardiomyocyte apoptosis (p < 0.01). Furthermore, punicalagin could inhibit the overexpression of NLRP3, caspase-1, and GSDMD via immunohistochemistry (p < 0.01). Punicalagin inhibited the protein levels of NLRP3, caspase-1, ASC, GSDMD, and GSDMD-N (p < 0.05, p < 0.01). Punicalagin reduced the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 (p < 0.05, p < 0.01). Conclusions Punicalagin may provide a useful treatment for the future myocardial protection.

Effect of extracellular adenosine triphosphate hydrolysis by apyrase on bleomycin-induced circulating and alveolar mononuclear phagocyte activation and lung inflammation.

Effect of extracellular adenosine triphosphate hydrolysis by apyrase on bleomycin-induced circulating and alveolar mononuclear phagocyte activation and lung inflammation.

Bioinformatics analysis and identification of dysregulated POSTN in the pathogenesis of keloid.

Keloid is a benign fibro-proliferative dermal tumour formed by an abnormal scarring response to injury and characterised by excessive collagen accumulation and invasive growth. The pathophysiology of keloids is complex, and the treatment for keloids is still an unmet medical need. Here, we investigated the transcriptional gene that influences keloid development by comparing keloid, non-lesioned keloid skin and normal skin as well as keloid fibroblast and normal fibroblast (GSE83286, GSE92566, GSE44270). Based on the analysis, 146 up-regulated genes and 48 down-regulated genes were found in keloid tissue compared with normal skin and keloid no-lesioned skin. Eleven genes were further identified by overlapping the DEGs from keloid tissue described previously with DEGs in keloid fibroblast. The overlapped genes included PRR16, SFRP2, EDIL3, GERM1, POSTN, PDE3A, GALNT5, F2RL2, EYA4, ZFHX4, and AIM2. POSTN is the most crucial node in PPI network, which mainly correlate to collagen-related genes. Moreover, siRNA knockdown identified POSTN is a crucial regulatory gene that regulates keloid fibroblast migration and collagen I, collagen III expression level. In conclusion, our study identified 11 hub genes that play crucial role in keloid formation and provided insights for POSTN to be the therapeutic target for keloid through bioinformatic analysis of three datasets. Additionally, our results would support the development of future therapeutic strategies.

Retrospective Study on the Effect of Adipose-Derived Stem Cells on the Proliferation and Apoptosis of Keloid Fibroblasts Through the Suppression of ITGA2.

Keloid is characterized by excessive collagen accumulation and fibroblast growth, which are fibroproliferative disorders of injured skin, causing functional limitations. Studies have shown that adipose-derived stem cells (ADSCs) inhibit the bioactivity and fibrosis of keloid fibroblasts. However, the molecular mechanism of this effect of ADSCs on keloid formation has not been fully elucidated. This in vitro study used fibroblasts obtained from keloids. A consensus gene co-expression network was constructed to focus on identifying consensus gene co-expression modules associated with keloid fibroblasts. Differentially expressed genes (DEGs) were identified between keloid fibroblasts and normal dermal fibroblasts. A functional enrichment analysis was also performed with the DAVID database. A weighted gene co-expression network analysis (WGCNA) was used to screen keloid-related modules using the "WGCNA" R package, followed by hub gene selection in modules from the Protein-protein interaction network through the STRING database. Keloid fibroblasts and ADSCs were extracted and cultured. Proliferation and apoptosis were examined using a 5-ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. We identified 302 DEGs overlapping with a consensus analysis of clusters and a differential expression analysis between keloid fibroblasts and normal dermal fibroblasts. Most of these were involved in collagen binding, extracellular matrix organization, and the PI3K-Akt signaling pathway. WGCNA analysis selected a keloid-associated brown module. ITGA2 was identified as a novel marker in hub genes from the PPI network based on the degree and function of collagen modulation. Furthermore, the proliferation ability of keloid fibroblasts cultured in ADSC medium was inhibited while apoptosis was dramatically increased. Overexpression of ITGA2 reversed the decrease in ADSC-induced apoptosis and increased ADSC-reduced proliferation. Our study demonstrated that activation of ITGA2 plays a crucial role in ADSC-induced keloid fibroblast apoptosis and anti-proliferation effects. These results also improved our understanding of the molecular mechanism of the pathogenesis of keloid in response to ADSCs and may contribute to the further development of keloid therapy.

High Levels of Heat Shock Protein 47 in the Aqueous Humor of Patients with Acute Primary Angle Closure

Introduction: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. Methods: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. Results: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (p = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (p = 0.023). Conclusion: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.