Proliferation Of Fibrous Tissue Research Articles

6615 Clinical features and genetic etiology of primary ovarian insufficiency in 46,XX children

Abstract Disclosure: F. Wang: None. X. Yin: None. X. Lan: None. P. Li: None. Purpose: The clinical features of primary ovarian insufficiency in 46,XX children were analyzed, the pathogenic genes of POI were screened, and the genetic etiology of primary ovarian insufficiency in children 46,XX was clarified. Method: The clinical data of 46,XX POI patients were collected, including uterine and ovarian ultrasound, serum follicle-stimulating hormone (FSH), estrogen, anti-mullerian hormone (AMH), chromosomal karyotype analysis, adrenal and thyroid function, and immune function. Whole exome sequencing (WES) and CNV were used to screen POI candidate genes. Novel mutations such as MCM8 gene were used to verify cell function. HE staining, immunohistochemistry, cell fluorescence, and Tunnel method were used to observe the changes in ovarian tissue structure. Construction overexpression plasmids of Mutant MCM8 gene in Hela cells. Result: 1. Clinical features of 46,XX POI: The age of onset of the children was 11.9∼16.1 years old. In addition to POI, the clinical phenotype showed height growth retardation. Among them, 4 cases were short stature, 3 cases were growth hormone deficiency, and 5 cases were backward in bone age. All of them showed elevated FSH (>25 IU/L), and 7 cases had low serum AMH (<0.5 ng/ml). 2.The Screening of POI candidate genes and pathogenicity analysis: 5 of the 10 children carried the mutations of the pathogenic genes with POI, that is, 2 cases (sisters of the same family) carried two novel heterozygous mutations of MCM8 gene, one infant carried two novel heterozygous mutations of CYP19A1 gene, and one case with delayed puberty carried one homozygous mutation of ZSW1M7 gene. 3.The MCM8 mutant were functionally validated: The sisters carried two novel mutations, namely p.C242R and p.S445*. The elder sister (the proband) showed POI, short stature and tumor susceptibility, while the younger sister showed a trend of gradual increase in FSH level and ovarian decline. The follicles of the proband disappeared and fibrous tissue proliferation, the MCM8 expression was lower, and the positive rate of cell apoptosis was higher than normal control. The downregulation of Bax and Capase3 expression in mutant MCM8 of Hela cell was delayed compared with wild type, indicating the persistence of apoptosis. Conclusion: 1. The clinical characteristics of 46,XX POI in children are ovarian hypoplasia, often combined with height growth retardation, biochemical manifestations of hypergonadotropic hypogonadism, decreased serum AMH, and karyotype 46,XX. 2.46,XX POI genetic etiology analysis found that five known POI-related pathogenic genes, namely CYP19A1, MCM8, and ZSW1M7, in which five novel mutations were identified.3.Mutant MCM8 promotes ovarian apoptosis by activating the Bcl-2/Bax/Caspase 3 pathway. Keywords: Primary ovarian insufficiency, short stature, apoptosis Presentation: 6/3/2024

A novel technique for skull base reconstruction in craniofacial fibrous dysplasia surgery using three-dimensional printing and a dental alginate mold: illustrative case.

Fibrous dysplasia is a rare and benign skeletal lesion characterized by fibrous tissue proliferation due to an abnormal osteogenesis replacing normal bone. An 18-year-old male with fibrous dysplasia of the left sphenoid, ethmoid, orbit, and frontal bones was managed with excision and skull base reconstruction. After complete removal of the tumor, skull base reconstruction was commenced by making a reverse temporalis flap and placing it over the opened paranasal sinuses for a robust vascularized graft, followed by an abdominal fat graft, and then a pedicled pericranal flap was added to complete the multilayer onlay graft. To recreate the skull base, a mirror image of the contralateral skull base was constructed using three-dimensional (3D) printing, and the 3D-printed model was sterilized prior to the surgery. Intraoperatively, the model was then pressed onto dental alginate gel to make a negative mold. This was used to make the definitive flap using polymethylmethacrylate. Temporoplasty was also performed using polymethylmethacrylate to fill the defect left by the temporalis graft. The patient recovered well following the procedure. Appropriate, personalized skull base reconstruction techniques can be successfully done with 3D printing using alternative low-cost materials and implements, especially following resection of cases like craniofacial fibrous dysplasia. https://thejns.org/doi/10.3171/CASE24262.

Multidepth quantitative analysis of liver cell viscoelastic properties: Fusion of nanoindentation and finite element modeling techniques.

Liver cells are the basic functional unit of the liver. However, repeated or sustained injury leads to structural disorders of liver lobules, proliferation of fibrous tissue and changes in structure, thus increasing scar tissue. Cellular fibrosis affects tissue stiffness, shear force, and other cellular mechanical forces. Mechanical force characteristics can serve as important indicators of cell damage and cirrhosis. Atomic force microscopy (AFM) has been widely used to study cell surface mechanics. However, characterization of the deep mechanical properties inside liver cells remains an underdeveloped field. In this work, cell nanoindentation was combined with finite element analysis to simulate and analyze the mechanical responses of liver cells at different depths in vitro and their internal responses and stress diffusion distributions after being subjected to normal stress. The sensitivities of the visco-hyperelastic parameters of the finite element model to the effects of the peak force and equilibrium force were compared. The force curves of alcohol-damaged liver cells at different depths were measured and compared with those of undamaged liver cells. The inverse analysis method was used to simulate the finite element model in vitro. Changes in the parameters of the cell model after injury were explored and analyzed, and their potential for characterizing hepatocellular injury and related treatments was evaluated. RESEARCH HIGHLIGHTS: This study aims to establish an in vitro hyperelastic model of liver cells and analyze the mechanical changes of cells in vitro. An analysis method combining finite element analysis model and nanoindentation was used to obtain the key parameters of the model. The multi-depth mechanical differences and internal structural changes of injured liver cells were analyzed.

The role of apoptosis, immunogenic cell death, and macrophage polarization in carbon ion radiotherapy for keloids: Targeting the TGF-β1/SMADs signaling pathway

Keloids, characterized by excessive extracellular matrix (ECM) deposition and aberrant fibrous tissue proliferation, present significant therapeutic challenges due to their recalcitrant and recurrent nature. This study explores the efficacy of Carbon Ion Radiotherapy (CIRT) as a novel therapeutic approach for keloids, focusing on its impact on fibroblast proliferation, apoptosis induction, immunogenic cell death (ICD), macrophage polarization, and the TGF-β/SMAD signaling pathway. Utilizing a murine model of keloid formed by subcutaneous injection of zeocin in C57BL/6 mice, we demonstrated that CIRT effectively reduces collagenous fiber synthesis and collagen production in keloid tissues. Further, CIRT was shown to inhibit keloid fibroblast proliferation and to induce apoptosis, as evidenced by increased expression of apoptosis-related proteins and confirmed through flow cytometry and TUNEL assay. Notably, CIRT induced mitochondrial stress, leading to enhanced immunogenicity of cell death, characterized by increased expression of ICD markers and secretion of interferon-γ. Additionally, CIRT promoted a shift from M2 to M1 macrophage polarization, potentially reducing TGF-β release and mitigating ECM deposition. Our findings suggest that CIRT mediates its therapeutic effects through the inhibition of the TGF-β/SMAD signaling pathway, thereby attenuating ECM formation and offering a promising avenue for keloid treatment. This study underscores the potential of CIRT as an innovative strategy for managing keloids, highlighting its multifaceted impact on key cellular processes involved in keloid pathogenesis.

Polymeric Dural Biomaterials in Spinal Surgery: A Review.

Laminectomy is a commonly performed surgical procedure by orthopedic and neurosurgeons, aimed at alleviating nerve compression and reducing pain. However, in some cases, excessive proliferation of fibrous scar tissue in the epidural space post-surgery can lead to persistent and intractable lower back pain, a condition known as Failed Back Surgery Syndrome (FBSS). The persistent fibrous tissue causes both physical and emotional distress for patients and also makes follow-up surgeries more challenging due to reduced visibility and greater technical difficulty. It has been established that the application of biomaterials to prevent epidural fibrosis post-lumbar surgery is more beneficial than revision surgeries to relieve dural fibrosis. Hydrogel-based biomaterials, with their excellent biocompatibility, degradability, and injectability and tunable mechanical properties, have been increasingly introduced by clinicians and researchers. This paper, building on the foundation of epidural fibrosis, primarily discusses the strategies for the preparation of natural and polymeric biomaterials to prevent epidural fibrosis, their physicochemical properties, and their ability to mitigate the excessive proliferation of fibroblasts. It also emphasizes the challenges that need to be addressed to translate laboratory research into clinical practice and the latest advancements in this field.

Perioperative Anesthetic Considerations for Catheter-Based Pulmonary Vein Interventions in Fibrosing Mediastinitis.

IntroductionFibrosing mediastinitis is a rare disease characterized by abnormal proliferation of fibrous tissue, causing compression, and narrowing of the airway, blood vessels and other mediastinal structures, including the pulmonary veins. Catheter based interventions are available palliative strategies. Due to the complex nature of the disease and the profound respiratory and hemodynamic sequela that may ensue, anesthetic management requires meticulous interdisciplinary planning. MethodsWe performed a retrospective descriptive study including patients with Fibrosing Mediastinitis undergoing catheter-based interventions for pulmonary vein stenosis from January 2020 to April 2024. A total of fourteen patients underwent chart review and we reported patient sex, preprocedural pulmonary artery pressures, comorbidities, lung isolation strategies, intra-procedural anesthestic complications, post procedural ICU admissions and length of stayResults: All patients underwent pulmonary vasculature angioplasty, with or without stent placement, under general anesthesia with lung isolation capabilities and echocardiogram guidance. 11 of 18 (61%) cases were uncomplicated. 4 of 18 (22%) required unanticipated postoperative ICU care, 2 (11%) in the setting of pulmonary hemorrhage, one due to hypoxic respiratory failure, and one due to difficult airway. One patient developed self-limiting postoperative hemoptysis in two different occasions and one patient developed a vascular access related complication. Mean hospital length of stay (LOS) was 2.6 days (0-13 days) and mean ICU LOS was 1.75 days (1-4 days). One patient presented 6-weeks postoperatively with massive hemoptysis likely secondary to PV rupture and passed away following a protracted ICU course. ConclusionPatients with FM can achieve successful intraprocedural outcomes by ensuring a comprehensive understanding of the disease, addressing significant anesthetic concerns and considerations, and engaging a multi-disciplinary team.

Clinical and Pathoanatomical Characteristics of Hypoplastic Left Heart Syndrome a Clinical Case

Hypoplastic left heart syndrome (HLHS) is a common congenital heart defect, accounting for 4 to 16% of cases, and is one of the most prognostically unfavorable, involving single-­ventricle hemodynamics. HLHS involves hypoplasia of the left ventricle, often in combination with atresia and/or stenosis of the aortic and/or mitral valves, as well as hypoplasia of various parts of the aorta. Intrauterine reduction in blood flow to the left heart structures at early stages of fetal development subsequently leads to severe changes in cardiac structures, often not amenable to surgical correction. Objective. To study the clinical and morphological features of HLHS using a clinical case as an example. Materials and Methods. The patient was a child from the first pregnancy, which was complicated by anemia and first-­trimester preeclampsia. The defect was diagnosed prenatally at 23/24 weeks. At 39 weeks, labor was induced, and the infant was hospitalized in the intensive care unit with symptoms of cardiac and respiratory failure. On the 6th day of life, surgical treatment was performed — a Norwood operation, which is a single-­ventricle hemodynamic surgical correction of the defect. Despite intensive care measures, multiple organ failure progressed, leading to the development of disseminated intravascular coagulation (DIC) and subsequent death on the 10th day of life. Results. Autopsy, including staining of the myocardium with Masson’s trichrome and hematoxylin and eosin, showed pronounced plethora of the microcirculatory vessels with formation of erythrocyte thrombi. Pronounced perivascular edema and fraying of muscle fibers were detected. Fibroelastosis of the endocardium of the left ventricle was observed, characterized by pronounced sclerotic thickening due to significant proliferation of fibrous tissue, with the spread of connective tissue strands into the myocardium. Endocardial fibroelastosis is a component of HLHS and one of the determining factors in the outcome of cardiac surgery. Conclusion. The results of this work indicate the complexity of HLHS as a developmental defect, the severity of its clinical manifestations, and the limited prospects of currently existing surgical treatment methods. These patients may require heart transplantation in the first days of life. A potential alternative to early postnatal heart transplantation may be the development of methods for intrauterine correction of the existing developmental defect.

Diagnostic challenge of the brown tumors in developing country: A case series

Introduction and importanceBrown tumors are non-neoplastic reactive tissue with osteoclasts multinucleated giant cells, and vascular and proliferative fibrous tissue. Hemorrhage results in significant bone resorption caused by hyperparathyroidism. This study provides information about the diagnosis challenge for brown tumor cases. Case descriptionWe report four cases that experience pathological fractures with moderate pain, multiple lytic lesions, severe hypercalcemia, increased ALP (Alkaline Phosphatase), and PTH (Parathyroid Hormone). Abnormal parathyroid mass was found in ultrasound. A bone scan described increasing radio uptake in various bones, a whole body scan, or parathyroid scintigraphy with 99mTc-MIBI. Eventually, in all cases, the diagnosis of the brown tumor was confirmed through histopathological examination, which showed multiple nucleated giant cells with a deposit of hemosiderin pathognomonic for the brown tumor, and the diagnosis of primary hyperparathyroidism (PHPT) was confirmed in all cases. Clinical discussionThese cases show that initial misdiagnosis of brown tumors as other bone tumors. A definitive diagnosis of brown tumors requires more than just histological confirmation. A comprehensive evaluation encompassing laboratory tests, imaging studies, clinical symptoms, and a multidisciplinary orthopedic-oncology board discussion is essential. Observations show that treating hyperparathyroidism alleviates the osteolytic lesions caused by brown tumors, despite the lack of clinical guidelines. ConclusionBased on a review of the literature and our clinical experience, we recommend screening serum calcium, phosphorus, and PTH levels in patients presenting with multiple lesions and widespread bone pain. This screening aims to rule out multiple bone lesions caused by PHPT.

Identification of pivotal genes and crucial pathways in liver fibrosis through WGCNA analysis.

Liver fibrosis is a progressive liver disease with increasing incidence, yet its underlying pathogenic mechanisms remain incompletely understood. : This study aims to explore potential therapeutic targets for liver fibrosis using weighted gene co-expression network analysis (WGCNA) and experimental validation. We retrieved the microarray data (GSE174099) from the GEO database and performed differential expression analysis and WGCNA to identify co-expression modules associated with liver fibrosis. A module with the highest correlation to liver fibrosis was selected for further analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions and signaling pathways of the identified genes. Protein-protein interaction (PPI) networks were constructed using the STRING database. The correlation between core genes and immune cells was analyzed with the CIBERSORT algorithm. Additionally, pathological and molecular biology experiments were performed to validate the expression levels of core genes in liver tissue, including HE and Masson staining, immunohistochemistry, RT-qPCR, and Western blotting. We identified a total of 86 intersecting genes from the differential expression analysis and WGCNA. GO enrichment analysis revealed that these genes were involved in processes such as cellular response to cAMP, collagen-containing extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis highlighted the involvement of these genes in pathways like Cell Adhesion Molecules and the PI3K-Akt signaling pathway. Using Cytoscape software, we identified four core genes: Cftr, Cldn4, Map2, and Spp1. Pathological examinations showed that the experimental group exhibited significant fibrous tissue proliferation compared to the control group. Immunohistochemistry, RT-qPCR, and Western blotting analyses confirmed that these core genes were significantly upregulated in the experimental group (P< 0.05). This study identified four key genes (Cftr, Cldn4, Map2, Spp1) that are significantly associated with liver fibrosis. These genes are upregulated in liver fibrosis and could potentially as biomarkers for diagnosis and targets for therapeutic interventions.

Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.

Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD). The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction. Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-β, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD. TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Identification of novel immune-related signatures for keloid diagnosis and treatment: insights from integrated bulk RNA-seq and scRNA-seq analysis

BackgroundKeloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids.MethodBulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids.ResultsIn the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion.ConclusionIn summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

Persistent Depression of the Lambda Site with Progressive Skull Deformity May Be a Sign of Suture Closure: Case Series and Pathologic Consideration

Back groundFlat head syndrome (FHS) sometimes occurs when a baby maintains the same head position during the first several months of life causing a skull deformity. FHS usually improves with time and natural growth, however, some shows aggravation against conservative treatment. We reviewed pathologically proved early closure of skull suture that may have seen secondary to FHS. MethodsThe clinical and radiological findings of the patients who showed progressive skull deformity resembling FHS were retrospectively reviewed. All the patients underwent surgical treatment and pathological specimens were obtained. ResultsThe detected patients included two 5-month-old infants and one 1-year-old infant. The formers were conservatively treated without any obvious premature suture closure on computed tomography (CT), and later developed progressive tower-like skull deformities. The infants were diagnosed with possible premature fusion of Lambda site and underwent removal around lambda depression (LD). The latter showed evident sagittal suture closure on CT with digital markings, and was diagnosed with increased intracranial pressure and underwent cranioplasty of posterior expansion. Histopathological specimens obtained from the patients’ resected sutures showed irregularly narrowed suture structure with ossification and fibrous tissue proliferation within them, supporting the diagnosis of premature closure of the sagittal sutures. Their postoperative courses were uneventful, and their skull deformities subsequently improved. ConclusionsConservative therapy-resistant progressive occipital skull deformity with LD may be a sign of early suture closure, even if CT does not show obvious suture closure. The findings are helpful for early diagnosis and might lead to minimal invasive surgery if needed.

Venous retrograde approach for endovascular angioplasty in chronic total pulmonary vein occlusion -a case report

IntroductionFibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc.Case presentationAn aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent.ConclusionsThis report may provide new management ideas for the interventional treatment of PV occlusion.

Magnetic Resonance Imaging of Cyclops Lesion in Patients With Non-reconstructed Anterior Cruciate Ligament.

Introduction The term cyclops lesion refers to localized anterior fibrosis, which is the abnormal proliferation of fibrous tissue in a joint that develops in the anterior aspect of the intercondylar notch. It is a known cause of extension loss of the knee after anterior cruciate ligament (ACL) reconstruction; however, it can be found in patients who have not undergone any surgical repair of the ACL. The term "cyclops lesion" was given based on the arthroscopic appearance of the fibrous nodule and vessels that resemble an eye. The purpose of this study is to highlight the existence of cyclops lesions in non-operated knees. Methods We conducted a study on 10 patients who were subjected to an MRI knee in a Siemens Magnetom Vida 3 Tesla (Erlangen, Germany) machine. We retrospectively analyzed all 10 cases in our institution from July 2021 to March 2022. These subjects had a previous history of trauma, and they presented with complaints of pain and difficulty in knee extension but no history of previous ligament repair. All patients underwent an MRI examination. When a cyclops lesion was revealed on MR imaging, the signal-intensity characteristics, location, and size were documented. Results There were a total of 10 patients included in the study, of whom eight were males and two were females. The most common clinical presentation in all our cases was difficulty in the extension of the knee, while there was associated instability and difficulty in walking in some patients. There was a demonstrable cyclops lesion near the tibial attachment of ACL in eight (80%) patients, whereas it was found to be located just lateral to the anterior intercondylar notch in the rest of the two (20%) patients. Conclusion MRI isaneffective tool to evaluate unexplained pain, functionallimitations,and limited range ofmotioninpatients with suspected arthrofibrosis.MRI also helpsdeterminethe extent offibrosisinvolvement andexcludes other complications that may have a similar clinicalpicture.

Case report: Ossifying fibroma

Ossifying fibroma is a benign fibro-osseous tumor, also known as central fibro-osteoma, cementoossifying fibroma, cementing fibroma. This neoplasm arises from the periodontal ligament and shows slow growth and proliferation of cellular fibrous tissue with varying amounts of osseous products such as bone, cementum or a mixture of both. Ossifying fibroma is a localized, asymptomatic swelling with cortical expansion in the mandible rather than the maxilla in mandible in the premolar and molar region in the third to fourth decade of life with female predilection. Radiologically, the lesion shows a welldefined, mixed radiolucent-radiopaque internal structure. Ossifying fibromas can grow to large sizes resulting in aesthetic and functional deformities. Hence, we present a classic case of an 18-year-old male patient with ossifying fibroma on the left body of the mandible, with all clinical, radiological and histopathological features, along with a brief discussion. Keywords: ossifying fibroma, benign fibro-osseous tumor, central fibro-osteoma, cemento-ossifying fibroma, cementifying fibroma.

Acute Toxicity and Hepatoprotective Influence of Hypericum perforatum Against Thioactamid-Induced Liver Fibrosis in Rats

Background: Hypericum perforatum (MEHP) is a broadly used therapeutic plant exhibiting numerous bioactivities. The present study evaluates acute toxicity and hepatoprotective effects of MEHP against thioacetamide (TAA)-induced liver injury in rats. Methods: The toxicity trial included a single oral administration of 2000 and 5000 mg/kg to rats. In the hepatoprotective experiment, 30 adult rats were arbitrarily clustered into 5 groups: Normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received 3 oral doses/week of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEHP, respectively. In addition, group B-E received 3 injections of 200 mg/kg TAA in a week for 60 days. Results: The results have shown a lack of any toxic signs in rats following oral administration of up to 5000 mg/kg. The hepatoprotective evaluations revealed a noticeably lower hepatic injury in MEHP-treated rats shown by reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&amp;E and Masson trichrome stains) showed a significant inhibitory potential of MEHP on the incidence rate of hepatic lesions represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEHP treatment meaningfully decreased proliferating cell nuclear antigen and α-SMA (myofibroblasts) in liver parenchymal tissues as well as improved redox (up-regulated SOD, CAT, GPx, and down-regulated MDA) and inflammatory state (decreased serum TNF-α and IL-6 cytokines) compared to fibrosis control rats. In addition, MEHP treatment caused significant restoration of serum liver biomarkers (enzymes and proteins) against TAA-induced hepatotoxicity. Conclusion: The present hepatoprotectives of MEHP could be attributed to its chemical contents (hypericin, hyperforin, quercitrin, and p-coumaric acid) that may validate it as a therapeutic additive for liver fibrosis after some pharmacological evaluations.

An insight into the epidemiology of foodborne zoonotic fascioliasis in small ruminants in northwestern region of Bangladesh.

Fascioliasis is one of the most common foodborne zoonotic infection of ruminants in Bangladesh. To estimate the prevalence and associated risk factors of fascioliasis and extent of liver damage, 825 livers of sheep and goats were randomly inspected during onsite slaughterhouse visiting in Naogaon, Natore, Rajshahi and Joypurhat districts. The overall prevalence of fascioliasis was 25.09% and significantly (P = 0.008) higher in goats (26.11%) than sheep (24.00%). During gross inspection, Fasciola infected livers were increased in size, fibrosed, fatty, multiple white or reddish necrotic foci on the parietal surface, hard to cut, calcified, and numerous mature and immature flukes were also observed. In histoarchitecture, inflammatory cell infiltration in the hepatic parenchyma and periportal area, fibrous connective tissue proliferation around necrotic area, hyperplastic bile duct, congestion, and primary biliary cirrhosis were seen in acute and chronic fascioliasis. Epidemiological investigations revealed that fascioliasis was higher in goats than sheep. Age, sex, BCS and season were found to have statistically significant associations with fascioliasis in goats. In case of sheep, age (OR = 5.8671; 95% CI: 2.9482-11.6757, P < 0.0001), sex (OR = 3.7317; 95% CI: 1.9052-7.3094, p < 0.0001), BCS (OR = 6.0346; 95% CI: 1.7986-20.2472, p < .0001), and season (OR = 8.2308; 95% CI: 3.9922-16.9693, p = < .0001) were also found to have statistically significant associations with fascioliasis. Results of the study can help for molecular epidemiology of fascioliasis in small ruminants to plan fluke control programs for safe food production.

A Rare Case of Congenital Corneal Keloids

Introduction : A corneal keloid is a uncommon ophthalmic condition that manifest as proliferation of fibrous tissue in the cornea and presents as an enlarging, white, elevated, well circumscribed corneal lesion. It is a relatively uncommon lesion that typically appears after surgery, injury, or corneal perforation. Pathological examination of the resected specimen leading to a diagnosis of corneal keloid.&#x0D; Case Illustration : A 6-year-old girl came with chief complaint was blurry vision in both eyes accompanied with a white opacity in her left eye that was gradually growing. The patient has been diagnosed with congenital glaucoma ever since birth. Nobody of her parents acknowledged having a history of inflammatory, infection, or ocular damage. At first glance, her visual acuity appeared to be light reflex in both eyes. Slit lamp biomicroscopy revealed a pearly white, enhanced opacity with sharp edges and smooth surface in the left eye (figure 1). New vessels were present in the lesion adjacent to the limbus. The patient is undergoing keloids excision, multilayer amnion membrane transplant and fine needle diathermy (figure2).&#x0D; Discussion : Corneal keloid can present at any age, present as a glistening white enlarging mass on the cornea and well demarcated from the adjacent normal tissue. Histopathologic examination demonstrates a thickened corneal epithelium overlying stroma and hyalinized collagen (figure 3).&#x0D; Conclusion : A corneal keloid should be suspected in cases of enlarging white glistening avascular corneal scars. Biopsy and histopathology confirmed the diagnosis.

Histological Assessment of the Effect Laser Irradiation on Full-Thickness Skin Wound Healing in Rabbits Models

Since there is currently no ideal treatment, wound healing impairment is a significant clinical challenge that is the subject of ongoing research into effective wound healing strategies. As a result, it has been demonstrated that low level laser therapy (LLLT), which is used for wound healing, can effectively control both the local and the systemic response. This study was conducted on 24 adult, clinically healthy male rabbits for this purpose. On each animal's back, full-thickness excisional wounds measuring 2 cm x 2 cm were created following sterile skin preparation. The animals were randomly split into two equal groups, each with twelve rabbits. In the group that acts as a control; 5 milliliters of phosphate-buffered saline was used to treat wounds. In the group treated; for the first seven days, the wounds were only treated with (LLLT) at a rate of 5/5 second at 8j/cm2. At the seventh, fourteenth, and 35th days of healing, histopathological biopsies were performed. The control group's histopathology revealed hemorrhage with inflammatory cell infiltration, primarily neutrophils, and congested blood vessels in the gap seven days after surgery. Necrotized neutrophils, hemolysis, and granulation tissue under the dermis were present in the gap at fourteen days. Between the muscle fibers, there was hemolysis. At 35 days, there was irregular proliferation of fibrous connective tissue, and congested blood vessels with mononuclear cell infiltration could be seen in the gap. At seven days, the treated group has completely sloughed the epidermis and a thin crust on the skin's surface with a small incision. In the dermis, there is a lot of infiltration of inflammatory cells, mostly lymphocytes and macrophages. There is also a lot of granulation tissue and a lot of adipose tissue with a lot of thick collagen network. At fourteen days, the epidermis' epithelial layers have healed completely and a keratinized layer is present. In the dermis, a proliferating and thick collagen network, scattered inflammatory cells, and regular fibrosis with hemorrhage and the development of a new B.V. At day 35, look for narrow scar tissue with complete epithelization, a keratinized layer above the epidermis, new vascularization with a lot of regular fibrosis and few regular collagen, new hair follicles, new blood vessels, and scattered macrophages. We concluded that full-thickness wound healing is positively influenced by the use of low level laser therapy (LLLT), which creates a microenvironment favorable to cell growth and differentiation.

Neutrophil extracellular traps (NETs) and Th-2 dominant immune responses in chronic granulomatous chromobalstomycosis.

Chromoblastomycosis (CBM), a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue, is caused by several dematiaceous fungi. The formation of granulomas, tissue proliferation, and fibrosis in response to these pathogenic fungi is believed to be intricately linked to host immunity. To understand this complex interaction, we conducted a comprehensive analysis of immune cell infiltrates, neutrophil extracellular traps (NETs) formation, and the fibrosis mechanism in 20 CBM lesion biopsies using immunohistochemical and immunofluorescence staining methods. The results revealed a significant infiltration of mixed inflammatory cells in CBM granulomas, prominently featuring a substantial presence of Th2 cells and M2 macrophages. These cells appeared to contribute to the production of collagen I and III in the late fibrosis mechanism, as well as NETs formation. The abundance of Th2 cytokines may act as a factor promoting the bias of macrophage differentiation toward M2, which hinders efficient fungal clearance while accelerates the proliferation of fibrous tissue. Furthermore, the expression of IL-17 was noted to recruit neutrophils, facilitating subsequent NETs formation within CBM granulomas to impede the spread of sclerotic cells. Understanding of these immune mechanisms holds promise for identifying therapeutic targets for managing chronic granulomatous CBM.