Excessive Fibrous Tissue Research Articles

Mesenchymal stem/stromal cells alleviate early-stage pulmonary fibrosis in a uPAR-dependent manner.

Pulmonary fibrosis, a debilitating lung disorder characterised by excessive fibrous tissue accumulation in lung parenchyma, compromises respiratory function leading to a life-threatening respiratory failure. While its origins are multifaceted and poorly understood, the urokinase system, including urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plays a significant role in regulating fibrotic response, extracellular matrix remodelling, and tissue repair. Mesenchymal stem/stromal cells (MSCs) hold promise in regenerative medicine for treating pulmonary fibrosis. Our study aimed to investigate the potential of MSCs to inhibit pulmonary fibrosis as well as the contribution of uPAR expression to this effect. We found that intravenous MSC administration significantly reduced lung fibrosis in the bleomycin-induced pulmonary fibrosis model in mice as revealed by MRI and histological evaluations. Notably, administering the MSCs isolated from adipose tissue of uPAR knockout mice (Plaur-/- MSCs) attenuated lung fibrosis to a lesser extent as compared to WT MSCs. Collagen deposition, a hallmark of fibrosis, was markedly reduced in lungs treated with WT MSCs versus Plaur-/- MSCs. Along with that, endogenous uPA levels were affected differently; after Plaur-/- MSCs were administered, the uPA content was specifically decreased within the blood vessels. Our findings support the potential of MSC treatment in attenuating pulmonary fibrosis. We provide evidence that the observed anti-fibrotic effect depends on uPAR expression in MSCs, suggesting that uPAR might counteract the uPA accumulation in lungs.

Exploring the Mechanisms and Preventive Strategies for the Progression from Idiopathic Pulmonary Fibrosis to Lung Cancer: Insights from Transcriptomics and Genetic Factors.

Background: Idiopathic pulmonary fibrosis (IPF) leads to excessive fibrous tissue in the lungs, increasing the risk of lung cancer (LC) due to heightened fibroblast activity. Advances in nucleotide point mutation studies offer insights into fibrosis-to-cancer transitions. Methods: A two-sample Mendelian randomization (TSMR) approach was used to explore the causal relationship between IPF and LC. A weighted gene co-expression network analysis (WGCNA) identified shared gene modules related to immunogenic cell death (ICD) from transcriptomic datasets. Machine learning selected key genes, and a multi-layer perceptron (MLP) model was developed for IPF prediction and diagnosis. SMR and PheWAS were used to assess the expression of key genes concerning IPF risk. The impact of core genes on immune cells in the IPF microenvironment was explored, and in vivo experiments were conducted to examine the progression from IPF to LC. Results: The TSMR approach indicated a genetic predisposition for IPF progressing to LC. The predictive model, which includes eight ICD key genes, demonstrated a strong predictive capability (AUC = 0.839). The SMR analysis revealed that the elevated expression of MS4A4A was associated with an increased risk of IPF (OR = 1.275, 95% CI: 1.029-1.579; p = 0.026). The PheWAS did not identify any significant traits linked to MS4A4A expression. The rs9265808 locus in MS4A4A was identified as a susceptibility site for the progression of IPF to LC, with mutations potentially reprogramming lung neutrophils and increasing the LC risk. In vivo studies suggested MS4A4A as a promising therapeutic target. Conclusions: A causal link between IPF and LC was established, an effective prediction model was developed, and MS4A4A was highlighted as a therapeutic target to prevent IPF from progressing to LC.

The Potential of Transforming Growth Factor-Beta1 (TGFβ1) in Fibrotic Tissue of Leiomyoma Specimens

Background: Fibrosis can define as the development of excessive fibrous tissue in an organ or tissue. In the situation of the uterus, leiomyoma or scar tissue may involve fibrosis state. The main feature of fibrosis in myoma is the existence of disordered smooth muscle cells and collagen that can be recognized via histological examinations in addition to extracellular component deposition. Leiomyoma is the most public uterine disorder that is mainly consists of smooth muscle cells, myo-fibroblast, and an obvious content of extracellular matrix. The myofibroblast in myoma lesion produced an elevated content of ECM. This paper displays the fibrotic circumstantial in leiomyoma and the mechanisms related to deposition of ECM components. Methods: this study involved (50) patients of 18-80 years old women diagnosed with benign uterine fibroid. Tumor samples were attained by consent from women undergoing hysterectomy or myomectomy at the Al Karama Teaching Hospitals in Kut, Wasit Province, Iraq between October 2022 to March 2023. samples from normal and fibroid were subjected to routein histological processing and subsequently stained with routein stains for general description, Masson Trichrome stain, Van Gieson's stain to visualize collagen content and histochemical stain (Alcian Blue-Periodic Acid Schiff) to evaluate the profile of mucins secreted via tumor cells.Normal myometrium and myoma tissue expression of TGF β1 growth factor was compared using immunohistochemical staining. Qupath and Image J programs were used to analysis the content of fibrous tissue within normal and myoma tissue. Results: Microscopical results revealed that myoma have a proliferation of overlap fusiform cells organized in bundles alienated by variable amounts of connective tissue fibers, enclosed peripherally by a pseudo capsule. Special stained sections analysis revealed deposition of extracellular martix components specially collagen fibers that vary within each nodular fibroid (intrafascicular, interfascicular) enclosed myocytes that reflect the state of fibrosis that appears as blue – green colors enclosed in Masson's trichrome stain, while in Van Gieson's stain appears as red color. Proliferative tumor cells were revealed via Alcian Blue-PAS stain in dark blue color. results showed distribution of perivascular fibers in myoma as compared with normal adjacent myometrium, which appears in red color in Van Gieson's stain. Immunostaining recorded the significantly higher intensity of TGF-β in the leiomyoma tissue than in the normal myometrium (P < 0.05). The effects of the TGF-β1 inhibitor significantly differed between normal myometrium and leiomyoma tissue, with a greater decrease in cell survival in the leiomyoma tissue (P < 0.05). Conclusion: highly fibrous tissue contents showed within myoma and perivascular than adjacent myometrium, these fibrous tissues were detected via special colours in both Masson Trichrome and Van Gieson's stains. The fibrous tissue within leiomyoma showed higher intensity to TGF than normal myometrium.

Prevalence of Increased QTc Dispersion Among Hypertensive Patients and Its Correlation to Clinical Risk Factors: A Hospital-Based Case-Control Study.

Background In Ghana and other sub-Saharan African countries, hypertension (HTN) prevalence is rapidly increasing. Hypertensive left ventricular hypertrophy (LVH) is associated with excess fibrous tissue deposition throughout the myocardium. This could lead to ventricular arrhythmias and sudden cardiac death. Increased corrected QT dispersion (QTcd) can cause ventricular repolarization and be used to identify patients at risk of ventricular tachyarrhythmia. The measurement of increased QTcd among hypertensive patients is a simple screening tool to stratify patients at cardiovascular risk. Methods A case-control hospital-based study was conducted on 200 consecutive hypertensive patients. Age- and sex-matched control groups of 200 normotensive individuals who gave informed consent were also recruited. The baseline clinical and demographic characteristics of participants were acquired using structured questionnaires. A physical examination and a resting 12-lead ECG were performed. Increased QTcd and LVH were determined. Results The mean age of hypertensive patients was 50.99±6.73 and 48.19±7.17 for the controls (p-value 0.63). The study population was predominantly female (1:2.4 male:female ratio). Higher mean values for QTcd and LVH (Sokolow-Lyon) were observed among hypertensive patients compared to controls. The prevalence of increased QTcd was 45.0% among hypertensive patients compared to 16.5% in controls (χ2=38.14, p-value <0.0000001, odds ratio = 4.14). Conclusion Increased QTcd is prevalent among hypertensive Ghanaians. Its measurement can be an effective non-invasive screening tool to risk-stratify hypertensive patients.

Clinical and Molecular Insights into Hypertrophic Scars and Keloids: A Literature Review

Background: Hypertrophic scars and keloids represent two distinct forms of abnormal wound healing, characterized by excessive fibrous tissue formation. Despite their prevalence, the pathophysiological mechanisms underlying their development and persistence remain incompletely understood. This literature review synthesizes current clinical and molecular insights into hypertrophic scars and keloids, aiming to highlight differences in their etiology, pathogenesis, and therapeutic responses. Methods: A comprehensive review of the literature was conducted, focusing on articles that provided significant insights into the clinical manifestations, genetic predispositions, molecular pathways, and treatment strategies related to hypertrophic scars and keloids. Experimental studies and clinical trials were included to encompass a wide range of data sources. Results: Hypertrophic scars are confined to the original wound boundary and may regress over time, whereas keloids extend beyond the wound margins and do not regress. Clinically, hypertrophic scars and keloids differ in their appearance, texture, and predilection sites. At the molecular level, these differences are underscored by distinct profiles of cytokine expression, growth factor activity, and extracellular matrix composition. Genetic studies have identified several predisposing factors, including specific gene mutations and polymorphisms. Treatment strategies vary; however, intralesional corticosteroids remain the first-line treatment for both conditions. Emerging therapies targeting specific molecular pathways offer potential for improved outcomes. Conclusion: Hypertrophic scars and keloids are complex conditions with distinct clinical and molecular characteristics. Understanding these differences is crucial for developing targeted and effective therapies. Future research should focus on unraveling the genetic basis of these conditions and exploring novel therapeutic targets. Enhanced knowledge of the pathogenic mechanisms will facilitate the advancement of personalized medicine approaches in the management of hypertrophic scars and keloids.

A randomised clinical trial study assessing the efficacy of 5% losartan potassium loaded in ethosomal gel to treat human keloids: a trial protocol

BackgroundKeloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids.MethodsIn this randomised clinical trial, 46 adults with keloids were divided into two treatment groups. One group of 23 participants received 5% losartan potassium loaded in ethosomal gel, while the other group of 23 participants received intralesional injections of 10% triamcinolone acetonide. Over 12 weeks, changes in POSAS 3.0 scores, degree of erythema and pigmentation, surface area, thickness, and pliability of the keloids will be measured at four different times: baseline, 4 weeks, 8 weeks, and 12 weeks. Statistical analysis will be conducted using SPSS software version 24, with a significance level of p < 0.05.DiscussionLosartan potassium is believed to be beneficial for keloid management because it inhibits the angiotensin II receptor, which plays a role in inflammation, proliferation, and fibrosis. This study examines the efficacy of 5% losartan potassium loaded in ethosomal gel for human keloids.Trial registrationClinicaltrial.gov identifier NCT05893108. Registered on 7 June 2023.

Understanding Fibrous Tissue in the Effective Healing of Rotator Cuff Injury.

The rotator cuff is a crucial group of muscles and tendons in the shoulder complex that plays a significant role in the stabilization of the glenohumeral joint and enabling a wide range of motion. Rotator cuff tendon tears can occur due to sudden injuries or degenerative processes that develop gradually over time, whether they are partial or full thickness. These injuries are common causes of shoulder pain and functional impairment, and their complex nature highlights the essential role of the rotator cuff in shoulder function. Scar formation is a crucial aspect of the healing process initiated following a rotator cuff tendon tear, but excessive fibrous tissue development can potentially lead to stiffness, discomfort, and movement limitations. Age is a critical risk factor, with the prevalence of these tears increasing among older individuals. This comprehensive review aims to delve deeper into the anatomy and injury mechanisms of the rotator cuff. Furthermore, it will inspect the signaling pathways involved in fibrous tissue development, evaluate the various factors affecting the healing environment, and discuss proactive measures aimed at reducing excessive fibrous tissue formation. Lastly, this review identifed gaps within existing knowledge to advance methods for better management of rotator cuff tendon injuries.

Surgical and Prosthodontic Management of Denture Induced Hyperplastic Lesion in Maxillary Arch – A Case Series

Denture irritation hyperplasia is a hyper plastic lesion of the oral mucosa which results from chronic irritation as a result of wearing poorly adapted dentures. It is most commonly seen in maxillary arch with female patients being mostly effected. The lesion varies in size from only a few millimeters to extending to involve the entire quadrant. The clinical management of denture induced hyperplasia depends upon the size of lesion and involves the elimination of causative factors, excision of excess fibrous tissue accompanied by an appropriate prosthetic rehabilitation. This case series presents the management of denture induced hyperplastic lesion of varying sizes present in maxillary arch by providing appropriate tissue rest and tissue conditioning as well as by surgical excision followed by new denture fabrication to achieve acceptable function for patients. KEYWORDS: Denture hyperplasia, Epulis fissuratum, Tissue conditioning, Prosthesis

Splenic Irradiation Prior to Allogeneic Hematopoietic Cell Transplantation for Patients with Myelofibrosis

Background: Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by excess fibrous tissue formation in the bone marrow. Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment for MF. Patients with MF often have compensatory splenic extramedullary hematopoiesis leading to splenomegaly, which is associated with delayed engraftment and decreased survival post-HCT. Several Janus kinase (JAK) inhibitors are approved to treat splenomegaly and systemic symptoms in MF patients. However, JAK inhibitor therapy does not always lead to complete resolution of splenomegaly. Therefore, splenic irradiation (RT) prior to HCT may benefit patients with persistent splenomegaly, yet research investigating outcomes of this therapeutic approach is limited. Methods: We conducted a single-center, retrospective cohort study of MF patients to characterize the feasibility of splenic RT and assess engraftment rates and post-transplant outcomes with this approach. Forty-eight MF patients who underwent HCT at Massachusetts General Hospital between 2011 to 2021 were identified using an institutional transplant database. Patient disease- and transplant-related characteristics were summarized according to splenic RT within 3 months prior to transplant. Results: Baseline disease- and transplant-related characteristics are displayed in Table 1. Among all patients, twenty-nine (60%) were male, and the median age was 67 years (range, 53-77). All patients received reduced intensity conditioning, with a majority (81%) receiving fludarabine with melphalan. Seventy-three percent of patients had a JAK2 mutation and 46% received ruxolitinib (RUX) prior to HCT. A total of 17 (35%) patients received splenic RT prior to transplant. Splenic RT ranged from 2 daily doses of 1 Gy to 5 daily doses of 1.5 Gy, with total radiation ranging from 2 Gy to 7.5 Gy. Splenic RT was administered at a median of 13 days prior to transplant (range, 7-69 days). All splenic RT patients had splenomegaly prior to transplant, and 11 (65%) were treated with RUX prior to HCT. Patients receiving splenic RT had significantly larger spleen sizes prior to transplant (23.1 v. 17.3 cm, p<0.01), and were more likely to have at least one high molecular risk (HMR) mutation than patients in the no RT group (83% v. 33%, p=0.01). For the entire cohort, the median days to neutrophil engraftment and platelet engraftment was 14 and 23, respectively. Among splenic RT patients, there was one case of primary graft failure and one case of secondary graft failure. The median days to neutrophil engraftment was 15 (IQR, 13-19) for the RT group and 13 (IQR, 12-14) for the no RT group (p=0.07). The median days to platelet engraftment was 32 (IQR, 25-108) for the RT group and 22 (IQR, 18-25) for the no RT group (p<0.01). Three splenic RT patients (18%) died early without platelet engraftment. When RUX was accounted, patients with RT and RUX had a substantially delayed platelet engraftment compared to no RT and/or no RUX (69.5 days vs 19.5-22.5 days, p=0.03) [Figure 1]. For the entire cohort, the 3-year overall survival (OS) and progression-free survival (PFS) was 67% (95%CI: 50%-79%) and 61% (95%CI: 45%-74%), respectively. The cumulative incidence of non-relapse mortality (NRM) and relapse was 26% (95%CI: 13%-40%) and 13% (95%CI: 5%-24%), respectively. Despite delayed platelet engraftment, survival outcomes were not different between RT and no RT, regardless of pre-HCT RUX exposure. Conclusion: Splenic RT administration prior to HCT appears feasible and associated with acceptable engraftment and clinical outcomes for MF patients with splenomegaly at the time of transplant. The persistence of massive splenomegaly at transplant following pre-transplant RUX is likely indicative of higher risk disease and remains associated with longer time to platelet engraftment, despite the addition of splenic RT. Larger prospective studies are required to fully assess the clinical impact of splenic RT in the transplant setting, especially in combination with other therapeutic strategies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Perilipin 5 Ameliorates Hepatic Stellate Cell Activation via SMAD2/3 and SNAIL Signaling Pathways and Suppresses STAT3 Activation.

Comprehending the molecular mechanisms underlying hepatic fibrogenesis is essential to the development of treatment. The hallmark of hepatic fibrosis is the development and deposition of excess fibrous connective tissue forcing tissue remodeling. Hepatic stellate cells (HSC) play a major role in the pathogenesis of liver fibrosis. Their activation via the transforming growth factor-β1 (TGF-β1) as a key mediator is considered the crucial event in the pathophysiology of hepatic fibrogenesis. It has been shown that Perilipin 5 (PLIN5), known as a lipid droplet structural protein that is highly expressed in oxidative tissue, can inhibit such activation through various mechanisms associated with lipid metabolism. This study aimed to investigate the possible influence of PLIN5 on TGF-β1 signaling. Our findings confirm the importance of PLIN5 in maintaining HSC quiescence in vivo and in vitro. PLIN5 overexpression suppresses the TGF-β1-SMAD2/3 and SNAIL signaling pathways as well as the activation of the signal transducers and activators of transcription 3 (STAT3). These findings derived from experiments in hepatic cell lines LX-2 and Col-GFP, in which overexpression of PLIN5 was able to downregulate the signaling pathways SMAD2/3 and SNAIL activated previously by TGF-β1 treatment. Furthermore, TGF-β1-mediatedinduction of extracellular matrix proteins, such as collagen type I (COL1), Fibronectin, and α-smooth muscle actin (α-SMA), was suppressed by PLIN5. Moreover, STAT3, which is interrelated with TGF-β1 was already basally activated in the cell lines and inhibited by PLIN5 overexpression, leading to a further reduction in HSC activity shown by lowered α-SMA expression. This extension of the intervening mechanisms presents PLIN5 as a potent and pleiotropic target in HSC activation.

Surgical outcomes in acute dacryocystitis patients undergoing endonasal endoscopic dacryocystorhinostomy with or without silicone tube intubation.

To establish the necessity of silicone tube intubation in acute dacryocystitis (AD) patients undergoing endonasal endoscopic dacryocystorhinostomy (En-DCR). Patients presenting with unilateral AD were randomly assigned to two treatment groups. En-DCR procedures were performed following lacrimal abscess formation, with the operation being performed with silicone intubation for patients in group B but not group A. Functional success was defined by an absence of additional AD episodes, no epiphora, and ostium patency as established via endoscopic evaluation or fluorescein irrigation. Operative success rates and demographic variables were compared between treatment groups. In total, 66 patients were analyzed in the present study (33 per group), with complete postoperative data having been successfully collected from 27 and 22 patients in group A and group B, respectively. All patients exhibited complete resolution of acute inflammation. Upon follow-up, granulation tissue was detected around the ostium at higher rates in group B (9/22, 40.9%) relative to group A (4/27, 14.8%). At the 12-month follow-up time point, patients in group A exhibited higher success rates (25/27, 92.6%) relative to patients in group B (20/22, 90.9%), but this difference was not significant. Cases of lacrimal passage reconstruction failure in both groups were attributed to excessive fibrous and/or granulation tissue formation proximal to the intranasal ostium. Given that these two operative approaches are associated with similar rates of operative success and in light of differences in granulation tissue formation, cost, and operative duration, these data do not support the routine silicone intubation of AD patients following En-DCR surgery.

Proteomic Biomarkers in the Cardiorenal Syndrome: Toward Deciphering Molecular Pathophysiology.

Cardiorenal syndrome (CRS) is defined by coexisting heart and renal dysfunctions. Malfunction of 1 organ may cause dysfunction of the other with variable causative disease that defines the type of CRS (1-5). Numerous studies showed that the prevalence of cardiovascular disease is increased in patients with chronic kidney disease (CKD). Similarly, CKD affects a large proportion of patients with heart failure. This overlap between primary heart or primary kidney disease blurs cause-effect inferences of the initiator/target organ. The classical subdivision of CRS in 5 categories does not provide pathophysiological suggestions for targeted intervention. It seems timely to revisit the value of CRS biomarkers in a pathophysiology-centered approach. We systematically reviewed the literature in CRS, which revealed 53 clinical studies describing the use of 44 biomarkers and 4 proteomic panels. All biomarkers are involved in at least one of the CRS comorbidities. Among the pathways affected, inflammation, aberrant glucose metabolism, neurohormonal activation, and oxidative stress are well described. There is growing evidence that fibrosis may be the "cornerstone" that unifies most of the pathways leading to CRS. Formation of excess fibrous connective tissue antedates CRS in many cases. This review highlights that biomarkers reflecting fibrosis may be of substantial clinical value in the early detection, prognostication, and guiding treatment of CRS. Biomarkers detecting changes in collagen turnover in the extracellular matrix of heart and kidney appear able to depict subclinical changes in the fibrotic remodeling of tissues and constitute a promising approach toward personalized intervention in CRS.

Hypoxia and transforming growth factor β1 regulation of long non-coding RNA transcriptomes in human pulmonary fibroblasts.

One of the key characteristics of idiopathic pulmonary fibrosis (IPF) is accumulation of excess fibrous tissue in the lung, which leads to hypoxic conditions. Transforming growth factor (TGF) β is a major mediator that promotes the differentiation of fibroblasts to myofibroblasts. However, how hypoxia and TGFβ together contribute the pathogenesis of IPF is poorly understood. Long non‐coding RNAs (lncRNAs) have regulatory effects on certain genes and are involved in many diseases. In this study, we determined the effects of hypoxia and/or TGFβ on mRNA and lncRNA transcriptomes in pulmonary fibroblasts. Hypoxia and TGFβ1 synergistically increased myofibroblast marker expression. RNA sequencing revealed that hypoxia and TGFβ1 treatment resulted in significant changes in 669 lncRNAs and 2,676 mRNAs compared to 150 lncRNAs and 858 mRNAs in TGFβ1 alone group and 222 lncRNAs and 785 mRNAs in hypoxia alone group. TGFβ1 induced the protein expression of HIF‐1α, but not HIF‐2α. On the other hand, hypoxia enhanced the TGFβ1‐induced phosphorylation of Smad3, suggesting a cross‐talk between these two signaling pathways. In all, 10 selected lncRNAs (five‐up and five‐down) in RNA sequencing data were validated using real‐time PCR. Two lncRNAs were primarily located in cytoplasm, three in nuclei and five in both nuclei and cytoplasm. The silencing of HIF‐1α and Smad3, but not Smad2 and HIF‐2α rescued the downregulation of FENDRR by hypoxia and TGFβ1. In conclusion, hypoxia and TGFβ1 synergistically regulate mRNAs and lncRNAs involved in several cellular processes, which may contribute to the pathogenesis of IPF.

RECURRENT AND MASSIVE HEMOPTYSIS: A CONSEQUENCE OF A RARE ETIOLOGY

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Fibrosing mediastinitis is an inflammatory reaction that results in excessive fibrous tissue formation in the mediastinum. It is usually attributed to histoplasmosis. It may affect the airways, great vessels, and other mediastinal structures secondary to robust inflammatory reaction to fungal antigens including granuloma formation and calcifications. The clinical presentation depends on which mediastinal structures being involved and the extent of the damage. Hemoptysis in fibrosing mediastinitis can be the result of bronchial invasion, necrotizing pneumonia, pulmonary or bronchial venous or arterial invasion. CASE PRESENTATION: 68-year-old Caucasian female with past medical history of chronic sinusitis, paroxysmal atrial fibrillation and fibrosing mediastinitis who presented to the emergency room (ER) complaining of three episodes of hemoptysis for 6 hours. The hemoptysis was estimated to be around 100 ml each time, bright red blood and associated with mild shortness of breath. Initial vitals were 104/54 mm Hg, heart rate of 110 bpm, respiratory rate of 22 cpm and Spo2 95% on 4L nasal cannula. The patient received one unit of PRBC for acute drop in hemoglobin from 14 gm/dl to 11 gm/dl. The patient was admitted to the intensive care unit (ICU) due to a concern of airway compromise and potential need for endotracheal intubation. The patient had episodes of massive hemoptysis over the last year and received corticosteroids intermittently without significant improvement. In the ICU, The clinical condition was relatively stable with normal vital signs yet continued to have hemoptysis. CT scan of the chest revealed mediastinal widening with diffuse calcified lymph nodes, broncholith extending into right main stem bronchus, superior vena cava stent and dilated main pulmonary arteries. Conventional angiography demonstrated dilatation of the two right sided intercostal bronchial trunks and multiple dilated intercostal arteries. Successful embolization of the above-mentioned arteries with microspheres was performed until achieving hemostasis. Subsequently, the patient did not experience further episodes of hemoptysis. The patient was discharged home in a stable clinical condition. DISCUSSION: Recurrent and massive hemoptysis is a consequence of numerous etiologies. We are reporting a rare case of fibrosing mediastinitis that presented as recurrent and massive hemoptysis. Diagnostic approach indicated the involvement of the bronchial and intercostal arteries. The involved vessels were treated successfully by embolization CONCLUSIONS: Recurrent massive hemoptysis is an uncommon clinical feature in these patients and associated with poor prognosis along with other local invasive process by the calcified mediastinal masses. Reference #1: Mediastinal fibrosis complicating histoplasmosis, Loyd JE1, Tillman BF, Atkinson JB, Des Prez RM. Reference #2: Chronic fibrous mediastinitis and superior vena caval obstruction due to histoplasmosis, Dis Chest. 1959 Apr;35(4):364-77. DISCLOSURES: No relevant relationships by Mukhtar Al-Saadi, source=Web Response No relevant relationships by Sai Katta, source=Web Response

Evaluation of Fibrolytic Effect of Bauhinia purpurea L.

Background: Mammary gland tissue (left half) revealed the presence of excess proliferation of fibrous tissue with disorganization of alveolar structures and the right half showed extensive fibrous tissue proliferation of mammary gland following intramammary inoculation of 2000 c.f.u. of Staphylococcus aureus. However, oral dosing of Bauhinia variegata L. bark powder at 6 gm/kg for 7 days and 3 gm/kg for another 7 days exhibited reduction of fibrous tissue in chronic mastitis. Objective: The fibrolytic effect of one week oral dosing of Bauhinia purpurea L. bark powder was studied in chronic mastitis with induced fibrosis as Bauhinia variegate L. is rarely available in plain land. Methods: Chronic mastitis with fibrosis was induced by intramammary inoculation of coagulase positive Staphylococcus aureus in group III and IV goats. Group I and III goats were injected with a single dose of ceftriaxone at 20 mg/kg intravenously, whereas group II and IV goats were orally administered Bauhinia purpurea L. bark powder at 6 g/kg for 7 days with a single dose of ceftriaxone at 20 mg/kg intravenously. Results: The t1/2β of ceftriaxone with Bauhinia purpurea L. stem bark powder in chronic mastitis increased significantly. Ceftizoxime was detected in plasma from 1 h to 48 h post dosing (pd) in group III and from 1 h to 96 h pd in group IV, respectively. Conclusion: Bark powder of Bauhinia purpurea L. at 6g/kg orally once daily increased the bioavailability of ceftriaxone and or ceftizoxime in milk due to its fibrolytic effect which was not reported earlier. Therefore, the Bauhinia purpurea L. bark powder having fibrolytic effect has the potential to reduce development of cancer.

Chemokine axis CXCL16/CXCR6 in the progression of fibrosis

Fibrosis is the common pathological basis of various lesions. It is mainly manifested as excess collagen deposition and fibrous connective tissue in tissues with destructed structures and impaired function. At present, the pathogenesis of fibrosis is still unclear, and no effective treatment or prevention for fibrosis is available. In recent years, numerous studies have shown that chemokine CXCL16 and its receptor CXCR6 play an important role in the development of fibrosis. This paper summarizes the biological characteristics of CXCL16/CXCR6 axis and its role in fibrosis. Key words: Fibrosis; CXCL16; CXCR6

Обоснование назначения и эффективность препарата Лонгидаза у больных хроническим простатитом

Chronic inflammation of the prostate leads to the formation of excess fibrous connective tissue, which hinders patients recovery and aggravates the symptoms. This study aimed to confirm the correlation between inflammation and prostatic fibrosis and the abnormalities of urodynamic and microcirculation in the prostate gland in humans, and the possibility of increasing the effectiveness of treatment of patients with chronic nonbacterial prostatitis using antisclerotic therapy. The study was carried out in two stages. At the first stage, pathomorphological findings, uroflowmetry data and degree of microcirculation disturbance were studied in 18 patients with chronic prostatitis who underwent prostate biopsy. At the second stage, an open prospective randomized comparative study was conducted. Two groups of patients with chronic nonbacterial prostatitis with signs of inflammation were formed. A control group (n=29) received standard treatment, rectal 0.5 methyluracil suppositories three times per week, 20 suppositories per course. In addition to the standard treatment, the patients of the study group (n=31) were administered Longidaza 3000 IU rectal suppositories also three times a week, 20 suppositories per course. Prostatic fibrosis worsens microcirculation by one and half times and statistically significantly negatively affects urodynamic. Using Longidaza resulted in neutralizing the negative consequences of the formation of excess fibrous connective tissue. Overall, an excellent and good effect was achieved in 21 (67.7%) and 9 (29.1%) patients of the study group, respectively; only in one case (3.2%) there was no effect. In the control group, an excellent and good effect was achieved in 14 (48.3%) and 11 (37.9%) patients, respectively; in 4 patients (13.8%) the treatment was considered of low effectiveness. Prevention of the fibrous connective tissue formation and regression of the fibrosis are pathogenetically valid. Anti-sclerotic enzyme therapy with Longidaza in the form of rectal suppositories results in a significant improvement in the symptoms of prostatitis, an increase in the maximum urinary flow rate and an improvement in the microcirculation of the prostate.

Evaluation of the developmental toxicity of perfluorooctanesulfonate in the Anuran, Silurana tropicalis.

A 150-day post-metamorphosis (dpm) partial lifecycle study exposing Silurana tropicalis to <0.03 (control), 0.06, 0.13 0.25, 0.5 and 1.0mg/L perfluorooctanesulfonate (PFOS) was conducted. A subset of specimens from the control and each treatment were evaluated at metamorphic completion. A significant increase in the median metamorphosis time was observed in the 1.0mg/L PFOS treatment relative to the control. A modest increase in the occurrence, but not severity, of mild follicular hypertrophy was found in thyroid glands from organisms exposed to the 0.62 and 1.1mg/L PFOS treatments. At 150dpm, a concentration-dependent increase in whole body PFOS residues was measured ranging from 29.6 to 163.5mg/kg in the 0.05 and 1.1mg/L PFOS treatments. Decreased body weight and snout-vent length were noted in specimens exposed to 1.1mg PFOS/L at the completion of metamorphosis. Body weight was reduced in the 1.1mg/L PFOS concentration; however, snout-vent length was not affected by PFOS exposure at 150dpm. An increased proportion of phenotypic males were noted in the 0.62 and 1.1mg/L PFOS treatments. Abnormal ovary development characterized by size asymmetry, necrosis and formation of excessive fibrous connective tissue was identified in females exposed to 0.29 and 1.1mg PFOS/L. Asymmetrically misshaped testes were found at 1.1mg/L PFOS. Results suggested that PFOS is capable of interfering with S. tropicalis growth before metamorphic completion and growth and gonad development during juvenile development.

Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts.

Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies.

BCL2 Regulates Differentiation of Intestinal Fibroblasts.

Fibrosis in patients with Crohn's disease (CD) results from an imbalance toward excessive fibrous tissue formation driven by fibroblasts. Activation of fibroblasts is linked to the B-cell lymphoma 2 (BCL2) family, which is involved in the induction of apoptosis. We investigated the impact of BCL2 repression on fibrogenesis. The model of dextran sodium sulfate (DSS)-induced chronic colitis and the heterotopic transplantation model of fibrosis were used. Following the administration of the BCL2 antagonist (ABT-737, 50 mg/kg/d), collagen layer thickness and hydroxyproline (HYP) content were determined. Fibroblasts were stimulated with the BCL2 antagonist (0.01-100 µM). BCL2, alpha smooth muscle actin (αSMA), and collagen I (COL1A1) were determined by quantitative polymerase chain reaction (qPCR), immunofluorescence microscopy (IF), and western blot (WB). mRNA expression pattern was determined by next-generation sequencing (NGS). Collagen layer thickness was significantly decreased in both DSS-induced chronic colitis and the transplantation model of fibrosis upon BCL2 antagonist administration compared with vehicle. Decreased HYP content confirmed the preventive effects of the BCL2 antagonist on fibrosis. In vitro, a significant increase in PI+/annexin V+ human colonic fibroblasts was determined by fluorescence-activated cell sorting upon treatment with high-dose BCL2 antagonist; at a lower dose, αSMA, COL1A1, and TGF were decreased. NGS, IF, and qPCR revealed decreased expression and nuclear translocation of GATA6 and SOX9, known for reprogramming fibroblasts. BCL2 antagonist administration partially prevented fibrogenesis in both fibrosis models. The BCL2 antagonist reduced the expression of TGFβ-induced factors involved in differentiation of myofibroblasts, and therefore might represent a potential treatment option against CD-associated fibrosis.