Fibrosis Disease Research Articles

High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches

Chronic kidney disease (CKD) ultimately causes renal fibrosis and end-stage renal disease, thus seriously threatens human health. However, current medications for CKD and fibrosis are inefficient, which is often due to poor targeting capability to renal tubule. In this study, we discover that biomimetic high-density lipoprotein (bHDL) lipid nanoparticles possess excellent targeting ability to injured tubular epithelial cells by kidney injury molecule-1(KIM-1) mediated internalization. Thus, we co-load anti-inflammatory drug triptolide (TP) and anti-fibrotic drug nintedanib (BIBF) on bHDL nanoparticles to treat CKD. Based on the targeted delivery and mutual enhancement of the efficacy of co-delivered drugs, the bHDL-based system effectively reduces kidney injury and alleviates renal fibrosis in different CKD mouse models. The mechanistic study shows that BIBF and TP synergistically remodel the fibrotic niches by decreasing inflammatory cytokines, limiting immune cell infiltration and inhibiting the activation of myofibroblasts. The bHDL vehicle also possesses high manufacturability, good safety and adequately reduces the toxicity of TP. Thus, this system is promising for the treatment of CKD and bHDL has good potential for delivering agents to damaged renal tubular epithelial cells.

Inhibition of Kv1.3 channel restrains macrophage M2 polarization and ameliorates renal fibrosis via regulating STAT6 phosphorylation.

Macrophages play crucial roles in regulating both homeostatic and inflammatory responses, with classical activated (M1) and alternatively activated (M2) subsets defined by the surrounding micro-environment. Renal fibrosis, developed from persistent inflammation, is worsened by M2 macrophages, yet the precise mechanisms underlying macrophage M2 polarization remain unclear. In this study, we investigated the role of Kv1.3, one of the primary potassium channels which is expressed in both innate and adaptive immunity, on macrophage M2 polarization and renal fibrosis. Our findings demonstrated that genetic or pharmacological inhibition of Kv1.3 significantly suppressed the expression of M2 markers and STAT6 phosphorylation. Furthermore, pharmacological inhibition of Kv1.3 by PAP-1 attenuated renal inflammation and fibrosis with decreased infiltration of macrophage infiltration and M2 polarization by employing the unilateral ureteral obstruction (UUO) renal fibrosis model. Mechanistically, we revealed that Kv1.3 was required for STAT6 phosphorylation in a mitochondria membrane potential dependent manner. Collectively, this study suggests that Kv1.3 is essential for macrophage M2 polarization and highlights the potential of Kv1.3 blockers as therapeutic agents for renal fibrosis and other M2 polarization-related diseases.

In silico development of a multi-epitope-based vaccine against Burkholderia cepacia complex using reverse vaccinology

BackgroundMultidrug-resistant Burkholderia cenocepacia and Burkholderia multivorans have emerged as significant pathogens, particularly in patients with cystic fibrosis (CF) and chronic granulomatous disease (CGD).ObjectiveGiven the absence of approved vaccines, this study aimed to identify potential vaccine candidates against these pathogens.MethodsThe complete genomes of B. cenocepacia and B. multivorans were retrieved from the GenBank. Surface-exposed proteins that were antigenic, non-allergenic, and non-homologous to human proteins were selected for further analysis. The conserved domains of the selected proteins were analyzed, and their presence was examined across 68 genomes. Subsequently, linear and conformational B-cell epitopes and human MHC II binding sites were identified. Highly conserved and immunogenic B-cell epitopes from outer membrane proteins (OMPs) were incorporated into a multi-epitope vaccine (MEV). Molecular docking analysis was performed to assess the interaction of the selected proteins. Finally, molecular dynamics (MD) simulations were conducted using GROMACS 2019 to evaluate the feasibility and dynamics of the interactions between the chimeric MEV and Toll-like receptor complexes, TLR2 and TLR4.ResultsOf 16,723 proteins identified in B. multivorans and B. cenocepacia strains, nine proteins (six OMPs and three extracellular) were selected as ideal candidates based on established criteria. These proteins had a molecular weight of 110 kDa and were present in ≥ 75% of the dataset of B. multivorans and B. cenocepacia genomes. In addition, molecular docking and MD indicated stable and feasible interactions between MEV and TLRs. The MEV-TLR4 system demonstrates the greatest stability and tightly bound interaction, with minimal fluctuations and high structural integrity. In contrast, the MEV-only system exhibits significant flexibility and dynamic behavior as a free ligand, while the MEV-TLR2 system balances stability and flexibility, showing a dynamic but stable interaction.ConclusionNine potential immunogenic proteins were identified as viable targets for vaccine development. An optimized MEV was explicitly designed for B. multivorans and B. cenocepacia. The novel MEV platform exhibited high binding affinity to immune receptors and favorable molecular docking characteristics. Although these findings are encouraging, additional in vitro and in vivo testing is necessary to validate the vaccine’s effects.

P0246 Predicting Operative Recurrence in Crohn's Disease Using a Nomogram Incorporating Histopathological Factors

Abstract Background Crohn's disease (CD) poses a substantial risk of disability and often necessitates recurrent surgical interventions. To date, no association between histologic activity and relapse in CD were found. Methods Data were retrieved from a prospective inflammatory bowel disease registry. Two blinded pathologists graded the inflammation and fibrosis of archived specimens from primary ileal or ileocolonic resections based on an established histopathological score. Factors associated with earlier operative recurrence were identified using a multivariate logistic regression model. A nomogram was constructed to predict reoperation, with model performance assessed using receiver-operating characteristic (ROC) curves and decision curve analysis (DCA). Results Among the 133 patients (68.4% male), the median time to reoperation was 31.9 months (IQR, 14.1-65.7 months). Fourteen reoperations were detected, 4 for abscess/fistula/perforation and 10 for stricture/stenosis. Fifty-four patients experienced endoscopic recurrence within a median time of 10.7 months (IQR, 4.53-18.9 months). Factors associated with reoperation included disease behavior (stricturing, OR 12.1, 95% CI 1.8-80.9; penetrating, OR 9.9, 95% CI 1.4-67.9) and the degree of intestinal fibrosis in the resected specimens (OR 12.1, 95%CI 1.2-126.6). A nomogram, incorporating fibrosis scores, smoking status, disease behavior, and perianal lesions, was established. Both ROC curve and DCA analysis indicated that the nomogram provided increased benefits for predicting reoperation. Conclusion The established nomogram, integrating fibrosis grading from resected specimens, serves as a practical tool for predicting reoperation in CD patients. This nomogram enables the identification of high-risk patients, facilitating proactive postoperative interventions to mitigate operative recurrence.

The fibronectin-targeting PEG-FUD imaging probe shows enhanced uptake during fibrogenesis in experimental lung fibrosis

Progressive forms of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), are deadly disorders lacking non-invasive biomarkers for assessment of early disease activity, which presents a major obstacle in disease management. Excessive extracellular matrix (ECM) deposition is a hallmark of these disorders, with fibronectin being an abundant ECM glycoprotein that is highly upregulated in early fibrosis and serves as a scaffold for the deposition of other matrix proteins. Due to its role in active fibrosis, we are targeting fibronectin as a biomarker of early lung fibrosis disease activity via the PEGylated fibronectin-binding polypeptide (PEG-FUD). In this work, we demonstrate the binding of PEG-FUD to the fibrotic lung throughout the course of bleomycin-induced murine model of pulmonary fibrosis. We first analyzed the binding of radiolabeled PEG-FUD following direct incubation to precision cut lung slices from mice at different stages of experimental lung fibrosis. Then, we administered fluorescently labeled PEG-FUD subcutaneously to mice over the course of bleomycin-induced pulmonary fibrosis and assessed peptide uptake 24 h later through ex vivo tissue imaging. Using both methods, we found that peptide targeting to the fibrotic lung is increased during the fibrogenic phase of the single dose bleomycin lung fibrosis model (days 7 and 14 post-bleomycin). At these timepoints we found a correlative relationship between peptide uptake and fibrotic burden. These data suggest that PEG-FUD targets fibronectin associated with active fibrogenesis in this model, making it a promising candidate for a clinically translatable molecular imaging probe to non-invasively determine pulmonary fibrosis disease activity, enabling accelerated therapeutic decision-making.

Alveolar nitric oxide concentration as a potential biomarker of fibrosis and active disease in pulmonary sarcoidosis: a pilot study.

Sarcoidosis is considered a T-helper (Th) 1 related disease, but a transition from Th1 to Th2 pathway activation has been postulated in sarcoidosis-associated pulmonary fibrosis (SAPF). Fraction of exhaled nitric oxide (FENO) is a marker of Th2 airway inflammation, but alveolar concentration of nitric oxide (CANO) can be measured to assess Th2 inflammation in the periphery of the lung. The aim of this study is to assess whether CANO can be considered a biomarker of SAPF or active pulmonary sarcoidosis. &#xD;Methods: In this single-center retrospective study, we compared exhaled NO levels of patients with pulmonary sarcoidosis without fibrosis (N=11) with those obtained from patients with SAPF (N=15). Clinical data, as well as respiratory function tests, were also analyzed. &#xD;Results: FENO (28.5 ± 16 ppb vs 30.9 ± 17.2 ppb, p=0.72) and CANO (4.4 ± 3.5 ppb vs 3.2 ± 1.7 ppb, p=0.73) levels did not differ significantly between patients with or without SAPF, even when dividing them according to treatment or disease activity. CANO appeared reduced in patients with active sarcoidosis (2.1 ± 0.8 ppb vs 4.1 ± 3 ppb, p<0.05).&#xD;Conclusion: CANO cannot be considered a biomarker of SAPF. Its lower level in patients with active disease confirms the prevalence of Th1 inflammation in granuloma formation and suggests its potential role as a biomarker of active pulmonary sarcoidosis, but further studies with larger samples are needed to confirm this hypothesis.&#xD.

Potential Protective or Pathogenic Roles of Parabacteroides distasonis in Diseases: A Narrative Review

Abstract Parabacteroides distasonis is a gram-negative, non-spore-forming, rod-shaped, anaerobic bacterium, and an important gut colonizer first isolated from human feces in 1933. Over more than 90 years of research, P. distasonis has been found to be associated with liver diseases such as liver fibrosis and non-alcoholic fatty liver disease, gastrointestinal diseases such as colitis and colorectal tumors and metabolic diseases such as obesity and diabetes, potentially playing a protective or pathogenic role in the occurrence and progression of these diseases. Herein, we elaborate on the biological characteristics, antibiotic resistance and potential roles of P. distasonis in these diseases, aiming to provide researchers with comprehensive information about P. distasonis and promote in-depth investigations into its safety and protective effects.

Ferroptosis in kidney disease: a bibliometric analysis from 2012 to 2024.

Ferroptosis, a novel concept of programmed cell death proposed in 2012, in kidney disease, has garnered significant attention based on evidence of abnormal iron deposition and lipid peroxidation damage in the kidney. Our study aim to examine the trends and future research directions in the field of ferroptosis in kidney disease, so as to further explore the target or treatment strategy for clinical treatment of kidney disease. A thorough survey using the Web of Science Core Collection, focusing on literature published between 2012 and 2024 examining the interaction between kidney disease and ferroptosis was conducted. VOSviewer, CiteSpace, and Biblioshiny were used for in-depth scientometric and visualized analyses. From 2012 to 2024, a total of 2,244 articles met the inclusion criteria for final analysis. The number of annual publications in this area of study showed a steady pattern at the beginning of the decade. The top 3 journals with the highest publication output were Renal Failure, Oxidative Medicine And Cellular Longevity, and Biomedicine & Pharmacotherapy. China and the United States had the highest number of publications. Central South University and Guangzhou Medical University as the most active and influential institutions. Documents and citation analysis suggested that Andreas Linkermann, Jolanta Malyszko, and Alberto Ortiz are active researchers, and the research by Scott J. Dixon and Jose Pedro Friedmann Angeli, as the most cited article, are more important drivers in the development of the field. Keywords associated with glutathione, lipid peroxidation, and nitric oxide had high frequency in the early studies. In recent years, however, there has been a shift towards biomarkers, inflammation and necrosis, which indicate current and future research directions in this area. The global landscape of the ferroptosis research in kidney disease from 2012 to 2024 was presented. Basic research and mechanism exploration for renal fibrosis and chronic kidney disease may be a hot spot in the future.

The advancement of targeted regulation of hepatic stellate cells using traditional Chinese medicine for the treatment of liver fibrosis.

Liver fibrosis, which is a precursor to cirrhosis in chronic liver diseases, is driven by various factors. The activation and proliferation of hepatic stellate cells (HSCs) are recognized as a crucial phase in the progression of liver fibrosis. Compared with western drug therapy, Traditional Chinese medicine (TCM) and herbal medicine not only have the advantages of multi-target and multi-pathways in the treatment of liver fibrosis, but also have high safety without toxic side effects. This paper aims to compile and analyze the active ingredients in TCM and their corresponding signaling pathways that target and modulate the phenotype of hepatic stellate cells, offering a potential treatment for hepatic fibrosis. The Literature information was obtained from the scientific databases PubMed, Web of Science and CNKI from January 2010 to June 2020 with the aim of elucidating the intrinsic mechanisms and roles of TCM and natural medicine in the treatment of LF. The search terms included "liver fibrosis" or "hepatic fibrosis", "traditional Chinese medicine" or "Chinese herbal medicine", "medicinal plant", "natural plant", and "herb". We described the antifibrosis activity of TCM and natural medicine in LF based on different signaling pathways. Plant medicine and herbal formulas regulated the related gene and protein expression via pathways such as TGF-β/Smad, PI3K/AKT/mTOR, MAPK and Wnt/β-catenin, which inhibit the proliferation, apoptosis, autophagy and activation of HSCs. By reviewing both domestic and international literature on TCM interventions in liver fibrosis, this study presents a thorough evaluation of recent research progress and the challenges faced in the clinical application of TCM for this condition. The goal is to lay a solid foundation for further in-depth studies and to strengthen the theoretical framework in this field. The inhibitory effect of TCM and natural medicine on fibrosis was reflected in multiple levels and multiple pathways, providing reasonable evidence for new drug development. To make TCM and natural medicine widely and flexibly used in clinical practice, the efficacy, safety and mechanism of action need more in-depth experimental research. It also seeks to provide a theoretical foundation for future research on targeted therapies for liver fibrosis and related diseases.

IGF1R Enhances Calcium Oxalate Monohydrate-Induced Epithelial-Mesenchymal Transition by Reprogramming Metabolism via the JAK2/STAT3 Signaling.

Background: Kidney stone disease is a major risk factor for impaired renal function, leading to renal fibrosis and end-stage renal disease. High global prevalence and recurrence rate pose a significant threat to human health and healthcare resources. Investigating the mechanisms of kidney stone-induced injury is crucial. Materials and Methods: We examined the relationship between insulin-like growth factor 1 receptor (IGF1R) and epithelial-mesenchymal transition (EMT) at three levels: in patients with kidney stones, in mice induced with glyoxalate crystals, and in HK2 cells stimulated with calcium oxalate monohydrate (COM). RNA sequencing (RNA-seq) and untargeted metabolomics were used to investigate IGF1R's biological mechanisms, followed by in vivo validation in mice. Results: IGF1R was elevated in the kidney stone model, which was significantly associated with EMT progression. RNA-seq analysis indicated that IGF1R enhances EMT through the JAK2/STAT3 pathway. Further experiments at mRNA and protein levels confirmed the activation of this pathway regulated by IGF1R, promoting EMT. Additionally, untargeted metabolomics revealed that IGF1R drives the activation of lactate dehydrogenase A (LDHA) in glycolysis, further facilitating EMT. In vivo experiments confirmed that IGF1R increases LDHA activity through the activation of the JAK2/STAT3 pathway, thereby enhancing the EMT. Conclusion: IGF1R promotes EMT in COM-induced kidney injury by activating LDHA via the JAK2/STAT3 signaling.

Emerging and Promising Keywords in Biomolecules and Therapeutics for 21st Century Diseases.

Recent technological advancements and environmental changes are leading to an increase in various diseases such as obesity, fibrosis, metabolic disorders, and degenerative diseases associated with aging. Additionally, micro- and nanoplastics are emerging as as potential contributors to many of these conditions, posing a serious threat to human health. This special issue aims to explore new directions and opportunities for future drug development through recent review articles published in the issue, focusing on these key medical topics.

Potential modifier genes for cystic fibrosis disease

Potential modifier genes for cystic fibrosis disease

New perspectives on markers implicated in signalling pathways that advance diabetic nephropathy and its therapeutic approaches

Diabetic nephropathy is the chronic loss of kidney function occurring due to diabetes mellitus. Due to increased sugar levels, there is disfunctioning of glomeruli, loss of protein in urine, and decrease in the levels of serum albumin that mainly leads to edema. The progression of renal disfunctioning starts when glomerular filtration rate is greater than 90ml/min. A large body of evidence indicates that oxidative stress is the main attributor involved in the progression of macro-vascular complications of diabetes. (ROS), NAD(P)H oxidase, advanced glycation end products (AGE), polyol pathway, uncoupled nitric oxide synthase (NOS), mitochondrial respiratory chain via oxidative phosphorylation, protein kinase C, mitogen-activated protein kinases, cytokines and transcription factors eventually cause increased expression of extracellular matrix (EC) genes with progression to fibrosis and end stage renal disease. Apart from these well-established pathways, major markers in the kidney disease which could work as potential targets has been explored like MCP-1, BMP-7, p38 MAPK, MiR-130b, HSP-27, AKT which further needs more research as they have shown promising results in their early level of studies. The present review aims to investigate the molecular targets involved in diabetic nephropathy, and to comprehend the intricate signalling pathways, such as JAK/STAT, BMP-7–Smad1/5/8 pathway, RhoA/ROCK, caspases, to which the aforementioned markers have either an independent or dependent relationship. If these signalling pathways are properly studied, these markers may aid in the treatment of the disease and its associated secondary effects such as nephropathy.

Association of neutrophil percentage to albumin ratio with gallstones: a cross-sectional study from the United States NHANES

Background and objectiveThe neutrophil percentage to albumin ratio (NPAR) is an emerging, costimulatory indicator of inflammation that is associated with a variety of diseases, such as non-alcoholic fatty liver disease, liver fibrosis, stroke, and cardiovascular disease. However, the relationship between NPAR and gallstones (GS) has not yet been explored. Therefore, this study aimed to evaluate the association of the NPAR with the odds of GS and the age of patients at the time of their first GS surgery.MethodsParticipants were selected from the National Health and Nutrition Examination Survey (NHANES) in the United States, a nationally representative survey. Logistic regression analysis and dose-response curve were performed to analyze the relationship between NPAR and the prevalence of GS. Multiple linear regression analysis and dose-response curve were used to analyze the association between NPAR and the age of patients at the time of their first GS surgery. Subgroup analyses further explored the relationships between NPAR and age, sex, race, body mass index, hypertension, and diabetes.ResultsIn total, 7805 adults aged > 20 years were included in this study, of whom 838 had a history of GS. After adjusting for all potential confounders, each 1-unit increase in NPAR was found to be associated with a 4% increase in the prevalence of GS (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02, 1.07) and an advancement in the age of the patient at the time of the first GS surgery by 0.35 years (β = − 0.35, 95% CI: − 0.68, − 0.02). Dose-response curves further confirmed that NPAR was positively associated with the prevalence of GS and negatively associated with the age of patients at the time of their first GS surgery. The results of the subgroup analyses suggested that after adjusting for all potential confounders, the positive association of NPAR with the prevalence of GS was more pronounced in the 40–59-year-old (OR: 1.07, 95% CI: 1.02, 1.12), male (OR: 1.07, 95% CI: 1.02, 1.12), non-Hispanic Black (OR: 1.06, 95% CI: 1.01, 1.12), non-hypertensive (OR: 1.06, 95% CI: 1.02, 1.10), and non-diabetic populations (OR=: 1.05, 95% CI: 1.02, 1.08).ConclusionsThe higher the NPAR, the higher the prevalence of GS, and the earlier the age of the patient at the time of the first GS surgery. Due to the nature of cross-sectional study, it is not possible to determine a causal relationship between them.

Circulating microRNA as promising biomarkers in hypertrophic cardiomyopathy: can advanced cardiac magnetic resonance unlock new insights in research?

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder associated with an increased risk of arrhythmias, heart failure, and sudden cardiac death. Current imaging and clinical markers are not fully sufficient in accurate diagnosis and patient risk stratification. Although known cardiac biomarkers in blood are used, they lack specificity for HCM and primarily stratify for death due to heart failure in overt cases. Non-coding RNAs, particularly microRNAs, have emerged as promising biomarkers due to their role in regulating gene expression in both healthy and pathological hearts. Circulating microRNA signatures may dynamically reflect the progression of HCM, offering potential utility in diagnosis and disease monitoring as well as inform biologic pathways for innovative therapeutic strategies. However, studying microRNAs in cardiovascular diseases is still in its early stages and poses many challenges. This review focuses on emerging research perspectives using advanced cardiac magnetic resonance techniques. We presume, that the search for circulating miR signatures associated with specific adverse myocardial features observed on cardiac magnetic resonance imaging - such as fibrosis, disarray, and microvascular disease - represents a promising direction in HCM research.

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.

Mucosa‐Interfacing Capsule for In Situ Sensing the Elasticity of Biological Tissues

AbstractMonitoring the elasticity of soft biological tissues in the gastrointestinal (GI) tract with minimal invasion holds promise for early diagnosis of intestinal fibrosis, colorectal cancer, and other diseases featuring abnormal elasticity. However, existing methods of sensing tissue elasticity have drawbacks such as insufficient resolution for elastography, and discomfort or the requirement of risky anesthesia for flexible endoscopes or implantable devices. Here a wirelessly actuated palpation mechanism is presented, integrated into a swallowable capsule device, offering in situ tissue elasticity measurement with minimal invasiveness. The approach employs a magnetic soft cantilever beam actuated by external magnetic fields to gently press against soft tissues. Mechanical stress and strain are monitored by an onboard magnetic sensor and a strain gauge, allowing for an accurate assessment of tissue elasticity. Additionally, wireless modules utilizing Bluetooth Low Energy (LE) and powered by a battery facilitate real‐time communication. The device operates under external magnetic field control, which can move freely over soft tissues during examinations and palpate suspicious areas. The elasticity sensing mechanism is validated and assessed on both phantom structures and ex vivo porcine colon tissues. The capsule device holds significant promise for assessing tissue physiological conditions and facilitating early disease diagnosis in hard‐to‐reach areas of the body.

Human placental stem cell-based therapies for prevention of abdominal adhesions: A prospective randomized preclinical trial.

Abdominal adhesions are networks of fibrotic tissues that form between organs postoperatively. Current prophylactic strategies do not reproducibly prevent adhesive small bowel obstruction across the entire abdomen. Human placental-derived stem cells produce an anti-inflammatory secretome that has been applied to multiple fibrosing diseases. The purpose of this project is to test human placental stem cell (hPSC)-based therapies for prevention of abdominal adhesions in a clinically relevant rat model. Fifty-four (n = 54, n = 6/group) male Sprague-Dawley rats (250-350 g) underwent model creation and treatment randomization under anesthesia. Experimental groups included human placental-derived stem cells (hPSC, 5 × 106 cells/10 mL Plasmalyte A), human placental-derived stem cells in a hyaluronic acid (HA-Mal-hPSC) hydrogel, the human placental-derived stem cell secretome from conditioned media in 10 mL Plasmalyte A, human placental-derived stem cells' conditioned media in a hyaluronic acid (HA-Mal-CM) hydrogel, Plasmalyte A (media alone, 10 mL), hyaluronic acid hydrogel alone (HA-Mal), Seprafilm (Baxter, Deerfield, IL), and the control groups, model with no treatment (MNT) and sham animals. Treatments were administered intraperitoneally, and the study period was 14 days postoperation. Adhesions were scored at necropsy and analyzed as the difference between means of an index statistic (Animal Index Score) versus MNT. Underlying molecular mechanisms were explored by functional genomic analysis and histology of peritoneal tissues. Hyaluronic acid hydrogel alone, HA-Mal-CM hydrogel, and Seprafilm significantly reduced the overall appearance of abdominal adhesions by mean Animal Index Score at 14 days versus MNT. Human placental stem cell, HA-Mal-hPSC hydrogel, HA-Mal-CM hydrogel, HA-Mal hydrogel alone, and Seprafilm significantly reduced the collagen content of injured peritoneal tissues. Human placental stem cell and HA-Mal-hPSC hydrogel suppressed expression of the most profibrotic genes. Conditioned media, HA-Mal hydrogel alone, and media alone significantly altered the expression of proteins associated with peritoneal fibrotic pathways. Human placental stem cell-based therapies reduce abdominal adhesions in a prospective randomized preclinical trial. This effect is supported by suppression of profibrotic genomic and proteomic pathways.

Clinical Profile and Non-invasive Predictors of Fibrosis in a Newly Diagnosed Non-Alcoholic Fatty Liver Disease Patient in a Tertiary Health Care Center of Nepal

Non-Alcoholic Fatty Liver Disease (NAFLD) represents a spectrum of histopathologic abnormalities ranging from simple steatosis to the more aggressive non-alcoholic steatohepatitis, characterized by steatosis, parenchymal inflammation, hepatocellular ballooning and other evidence of hepatic injury. The objective of this study is to evaluate the demographic and anthropometric profile of non-alcoholic fatty liver disease and non-invasive predictors of fibrosis. This is a hospital-based observational study. A total of 280 patients were included in this study from the Department of Gastroenterology, Tribhuvan University Teaching Hospital from January 2019 to August 2021 were included. Patients presenting with non-alcoholic fatty liver disease were mostly (29.64%) of 36-45 age group. Two-third of the patients (66.78%) were asymptomatic. The mean body mass index of patients was 28.10±4.10 kg/m2 and most of them (81.07%) had body mass index &gt;25 kg/m2. More than one third of the patients (40%) with non-alcoholic fatty liver disease had presence of metabolic syndrome. The mean (±SD) ultrasound attenuation parameter was 284.22±31.58 dB/m. Fatty liver index showed a positive and a medium strength correlation with fatty liver. On Spearman rank correlation, ultrasound attenuation parameter steatosis grading was correlated positively and strongly with the USG grading of fatty liver (p&lt;0.001). On Pearson correlation, APRI, NFS and FIB-4 were positive but weakly correlated with liver stiffness measurement by FibroTouch but still the correlation was statistically significant (p&lt;0.01). Fatty liver index has shown a good correlation with the presence of steatosis by a FibroTouch. Similarly, APRI showed the highest correlation in predicting liver stiffness in the population of Nepal. Other multicenter large scale prospective analytical studies would be required for further clarify of the results of such a kind of research. Bangladesh Med J. 2023 Sept; 52(3): 35-40

Interstitial lung disease: retrospective study of the prognostic impact of acute exacerbations.

Interstitial lung diseases have high mortality associated with hospitalization for decompensation. There are doubts about the factors involved in the progression of fibrosis, for example the role played by acute exacerbations. With this work, the authors intend to analyze whether there are predictive parameters of mortality related to exacerbations. A retrospective study was carried out of patients admitted to the Pulmonology department of Coimbra University Hospital Center for exacerbation of fibrosing lung disease between January 2019 and December 2020. These were classified as: idiopathic pulmonary fibrosis (IPF), fibrosing hypersensivity pneumonitis (FHP) and other fibrosing lung diseases. Statistical analysis was performed using SPSS 26.0 considering statistically significant p<0.05 values. The results show that IPF is associated with longer hospital stay in relation to fibrosing HP and other fibrosing lung diseases mean of 20.93 days (95% CI: 14.69-27.18) vs 11.8 days (95% CI: 1.05-17.22, p=0.023) vs 12.23 days (95% CI 2.06-15.34, p=0.007), respectively. Regarding mortality, there was no difference between IPF, PH and other fibrosing diseases (p=0.631). This study demonstrated that IPF, compared to PH and other fibrosing diseases, is associated with longer hospital stays, probably due to its progressive course despite the institution of corticosteroid therapy. As shown in previous studies, it was concluded that there is no difference in terms of mortality between IPF exacerbations and other forms of fibrosing lung disease.