Myofibroblastic Cells Research Articles

THE EXPRESSION OF ALPHA-SMOOTH MUSCLE ACTIN IN CONTRACTED SOCKET

Purpose: A contracted socket is considered a common complication in anophthalmic patients, with the resulting poor fitting of an ocular prosthesis. In severe cases where patients have had multiple previous reconstructive attempts, further socket contraction may result from fibrosis, leading to eventual surgical failure. Alpha-smooth muscle actin (?-SMA) is often used to identify pathologic fibroblasts. It may serve as a reliable marker for myofibroblast cells. The aim of the study was to find ?-SMA protein expression in myofibroblasts derived from orbital socket contracture. Methods: In this study, we observed five patients with contracted sockets who underwent fornicoplasty and buccal graft surgery from October 2022 to February 2023. Tissue samples were taken from the conjunctival fornix area during the surgery and then examined for ?-SMA expression. Result: In this study, there were 2 out of 5 (40%) positive ?-SMA expressions with history of recurrent contraction, 2 (40%) negative expressions with no history of recurrent contraction, and 1 result that could not be assessed due to the limited number of samples containing fibroblasts. Conclusion: ?-SMA levels can be detected in patients with contracted sockets. Patients with a history of recurrently contracted sockets have a tendency to express positive ?-SMA. This may allow for the need for the administration of antimetabolites in patients with recurrent contracted sockets to avoid recurrence of this contracted socket.

P-85 Inflammatory myofibroblastic tumor: An extremely rare tumor of the thyroid gland poses challenges in diagnosis and management

Abstract Introduction Inflammatory myofibroblastic tumor (IMT) is an exceedingly rare mesenchymal tumor characterized by myofibroblastic spindle cells and an inflammatory cell infiltrate. The clinical presentation of IMT in the thyroid gland varies widely, ranging from an asymptomatic thyroid nodule to a diffuse, rigid, fixed, and painful mass. While IMT of the thyroid gland is generally considered a benign borderline tumor with very low metastatic potential, its diagnosis and management can be intricate. Surgery remains the preferred treatment, with recurrence being rare following successful removal. Nonetheless, the optimal management of residual tumors is contentious and may involve a second surgery or the use of immunosuppressants and chemotherapeutic agents. Clinical Case A 47-year-old female patient presented with painless discomfort and stiffness around the thyroid gland. A neck ultrasound revealed a hypoechoic nodule measuring 21×12 mm on the left lobe and a hypoisoechoic heterogeneous nodule 35×28 mm in size on the right lobe of the thyroid gland. These nodules displayed low vascularity, and no pathologic lymph nodes were detected. Fine needle aspiration biopsies (FNABs) were performed on the nodules in both lobes at different times, indicating thyroiditis in the right lobe and spindle-shaped cells with atypia of uncertain significance in the left lobe. Subsequent evaluation of FNAB materials at a referral center suggested a high suspicion of lymphoid malignancy. The patient underwent thyroidectomy; however, the surgeon chose to preserve the left thyroid lobe due to its extreme fibrotic and stone-like consistency, thereby preserving recurrent laryngeal nerve function. Histological analysis confirmed the presence of an inflammatory myofibroblastic tumor characterized by spindle cells accompanied by abundant histocytes, plasma cells, and lymphocytes. The tumor cells exhibited positivity for SMA. Postoperative ultrasound revealed a residual tumor approximately 2 cm in size located in the left isthmus and adjacent left lobe, which remained stable over a 6-month follow-up period. Conclusion Our case highlights the potential for misdiagnosing IMT of the thyroid gland as malignant thyroid tumors. Furthermore, the management of a residual tumor presents a complex clinical challenge. The surgical team is reluctant to pursue a second surgery due to potential risks to recurrent laryngeal nerve function. In this session, we aim to solicit expert opinions and engage in interactive discussions regarding the management of the residual tumor in this specific case.

A Rare Case of Inflammatory Myofibroblastic Tumor Mimicking Fibrous Adhesions Resulting in Bowel Obstruction

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumors of unknown etiology composed of myofibroblastic cells admixed with inflammatory cells. Presented is a 72‐year‐old male hospitalized for severe abdominal pain and hematochezia with onset of associated symptoms of fever and sweats a few hours prior to abdominal pain. A computed tomography (CT) demonstrated left colonic thickening interpreted as partial obstruction, gross adhesions, and ischemia. At surgery, marked bowel ischemia from the distal transverse to proximal sigmoid colon was seen with extensive gross adhesions. Histopathology revealed a mesenteric mass chiefly composed of stellate‐to‐spindled myofibroblastic cells and fibrous adhesions, intermixed with lymphocytes, histiocytes, and plasma cells. The tumor was positive for desmin, smooth muscle actin, and keratin; tumor staging, grade, and postsurgical follow‐up were not completed as the patient expired postoperatively. Illustrated is a rare pathologic mimic of ischemic colitis with fibrous adhesions, IMT. Thus, it should not be assumed that fibrous adhesions are always the etiology of obstruction when “adhesions” between sections of bowel are noted radiologically or surgically.

Lorlatinib for the Treatment of Inflammatory Myofibroblastic Tumor after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas composed of myofibroblastic and fibroblastic cells, accompanied by inflammatory cell infiltration. Many IMTs exhibit clonal rearrangement of anaplastic lymphoma kinase (ALK). We herein report a 56-year-old woman with uterine IMT harboring a thrombospondin-1::ALK fusion that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Laboratory data before systemic therapy indicated increased interleukin-6 and severe leukocytosis. The patient was treated with lorlatinib; however, the response duration was approximately two months. Similar case reports need to be compiled and evaluated to elucidate the efficacy of lorlatinib in post-allo-HSCT IMT with ALK rearrangement.

Sunrays epiretinal membrane

Aim: To report a unique aspect of an opalescent, symmetrical, sun rays like epiretinal membrane (ERM), assessed with swept source optical coherence tomography (SS‐OCT).Methods: Patient was assessed with multimodal imaging: colour photography and SS‐OCT with B‐scan and en face imaging.Results: A 65‐year‐old male with hypertension and diabetes history, followed in our consultation for pre‐proliferative diabetic retinopathy (DR), lost of sight for two years, presented with progressive visual decrease in his left eye (LE). Best corrected visual acuity (BCVA) of the right eye was 8/10 without any sign of DR activity on fundus examination. BCVA of the LE was limited to hand motion. Anterior segment examination was unremarkable. Fundus examination highlighted the presence of opaque dense ERM lining the posterior pole mimicking a symmetrical wheel spoke or sunrays, centred by a foveal pigmented lesion. En face SS‐OCT showed patterned retinal folds and B‐Scan SS‐OCT showed a thick hyperreflective layer above the internal limiting membrane (ILM) associated to underlying retinal surface wrinkling. We also noted thickened disorganized retinal layers, ectopic inner foveal layers (EIFL) and loss of the foveal depression. The central bouquet assessed the presence of subretinal hyperreflective vitelliform‐like deposit associated to intraretinal hyperreflective foci corresponding to pigment migration.Conclusion: This case corresponds to the final stage ERM of Govetto classification. It reveals a migration process of retinal pigment cells towards inner retinal layers. The advent of high‐resolution SS‐OCT offered a better detection of ERM stages and alterations of the central bouquet, in order to improve our pathophysiological understanding. In fact, many hypotheses on ERM development processes were suggested. Glial cells and retinal pigment epithelial cells would undergo trans‐differentiation to a myofibroblastic pre‐retinal cells through the retina, via microdefects above ILM. Accumulated myofibroblastic cells, along with extracellular matrix deposition are the main precursors of ERM.

A Skin Inflammatory Myofibroblastic Tumor Penetrates Through Skull To The Dura: A Case Report

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) is currently accepted to be a true neoplasm with a wide spectrum of biological behavior, varying from benign lesions to the rare tumors which are multifocal and prone to recurrence. IMT is characterized by a proliferation of myofibroblastic spindle cells with an inflammatory infiltrate. It was first described in the lung and later on reported in various sites such as stomach, intestine, spleen, bone. Here we report a rare IMT case in that the tumor penetrates through skull and extends to the dura. Methods/Case Report A 29-year-old female presented with a slowly progressive upper head scalp mass of one-year duration. Magnetic resonance imaging showed a soft tissue mass that extended through the skull and into the dura. Patient denies headache, syncopal episodes, neck pain, back pain, radicular symptoms, weakness, ataxia, nausea, vomiting, bladder or bowel incontinence, saddle anesthesia, or changes from baseline hearing, vision, or speech. Grossly, serial sectioning of the scalp skin specimen revealed a well-circumscribed mass lesion with white, firm, and homogeneous cut surface, with no hemorrhage or necrosis identified. The lesion measured 7.0 x 6.5 x 1.7 cm in greatest dimension. The lesion involved the deep margin and extended to the skull and dura. On histopathological examination, the lesion was composed of variable admixture of spindle cells with eosinophilic cytoplasm and inflammatory cells comprising of plasma cells and lymphocytes. The spindle cells were positive for smooth muscle actin, CD10 (partial), and negative for AE1/AE3, ALK–1, CD34, CD68, CD117, Desmin, Myogenin, p53, S-100, and SOX-10. The Ki-67 showed a spindle cell proliferation index at about 2%. The patient successfully went through surgery and was followed up without complications. Results (if a Case Study enter NA) NA Conclusion Our case showed a rare IMT case harboring histologically benign features like low cellularity, minimal nuclear atypia, and low proliferative index, but demonstrating locally very aggressive biological behaviors. Complete surgical resection and close follow up are suggested to avoid recurrence. Further studies are needed in this field to design in-depth investigation for accurate diagnosis and better clinical outcomes.

Furin Regulates the Alveolarization of Neonatal Lungs in a Mouse Model of Hyperoxic Lung Injury.

Despite advances in treatment options, such as corticosteroid administration and less invasive respiratory support, bronchopulmonary dysplasia (BPD) remains an important prognostic factor in preterm infants. We previously reported that furin regulates changes in lung smooth muscle cell phenotypes, suggesting that it plays a critical role in BPD pathogenesis. Therefore, in this study, we aimed to evaluate whether it regulates the alveolarization of immature lungs through activating alveolarization-driving proteins. We first examined furin expression levels, and its functions, using an established hyperoxia-induced BPD mouse model. Thereafter, we treated mice pups, as well as primary myofibroblast cell cultures, with furin inhibitors. Finally, we administered the hyperoxia-exposed mice pups with recombinant furin. Immunofluorescence revealed the co-expression of furin with alpha-smooth muscle actin. Hyperoxia exposure for 10 d decreased alveolar formation, as well as the expression of furin and its target, IGF-1R. Hexa-D-arginine administration also significantly inhibited alveolar formation. Another furin inhibitor, decanoyl-RVKR-chloromethylketone, accumulated pro-IGF-1R, and decreased IGF-1R phosphorylation in myofibroblast primary cultures. Finally, recombinant furin treatment significantly improved alveolarization in hyperoxia-exposed mice pups. Furin regulates alveolarization in immature lungs. Therefore, this study provides novel insights regarding the involvement of furin in BPD pathogenesis, and highlights a potential treatment target for ameliorating the impact of BPD.

Intermittent actuation attenuates fibrotic behaviour of myofibroblasts

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood. Here, we use analytical, computational, and in vitro models to understand the response of human myofibroblasts (WPMY-1 stromal cell line) to intermittent actuation using soft robotics and investigate how actuation can alter the secretion of collagen and pro/anti-inflammatory cytokines by these cells. Our findings suggest that there is a mechanical loading threshold that can modulate the fibrotic behaviour of myofibroblasts, by reducing the secretion of soluble collagen, transforming growth factor beta-1 and interleukin 1-beta, and upregulating the anti-inflammatory interleukin-10. By improving our understanding of how cells involved in the FBR respond to mechanical actuation, we can harness this technology to improve functional outcomes for a wide range of implanted medical device applications including drug delivery and cell encapsulation platforms. Statement of significanceA major barrier to the successful clinical translation of many implantable medical devices is the foreign body response (FBR) and resultant deposition of a hypo-permeable fibrotic capsule (FC) around the implant. Perturbation of the implant site using intermittent actuation (IA) of soft-robotic implants has previously been shown to modulate the FBR and reduce FC thickness. However, the mechanisms of action underlying this response were largely unknown. Here, we investigate how IA can alter the activity of myofibroblast cells, and ultimately suggest that there is a mechanical loading threshold within which their fibrotic behaviour can be modulated. These findings can be harnessed to improve functional outcomes for a wide range of medical implants, particularly drug delivery and cell encapsulation devices.

PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response invitro and dramatically improves fibrosis invivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.

Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis.

Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They are involved in the production of extracellular matrix, the formation of the fibrous cap, and the underlying lipidic core via modulation processes in response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells and healthy vascular smooth muscle cells, smooth muscle cells are still widely used as a cellular model in atherosclerotic research. Methods and Results Here, we present a conditioned outgrowth method to isolate and culture myofibroblast cells from plaques. We obtained these cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that they keep their proliferative capacity for 8 passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, and DCN) and smooth muscle cell markers (ACTA2, MYH11, and CNN1). Single-cell transcriptomics reveals that the cells in culture closely resemble the plaque myofibroblasts. Chromatin immunoprecipitation sequencing shows the presence of histone H3 lysine 4 dimethylation at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque myofibroblasts can be efficiently transduced (>97%) and are capable of taking up oxidized low-density lipoprotein and undergoing calcification. Conclusions In conclusion, we present a method to isolate and culture cells that retain plaque myofibroblast phenotypical and functional capabilities, making them a suitable in vitro model for studying selected mechanisms of atherosclerosis.

Role of integrins in the development of fibrosis in the trabecular meshwork.

Primary open angle glaucoma (POAG) is a progressive and chronic disease exhibiting many of the features of fibrosis. The extracellular matrix (ECM) in the trabecular meshwork (TM) undergoes extensive remodeling and enhanced rigidity, resembling fibrotic changes. In addition, there are changes associated with myofibroblast activation and cell contractility that further drives tissue fibrosis and stiffening. This review discusses what is known about the integrins in the TM and their involvement in fibrotic processes.

A multicentric case study of fibroblastic and myofibroblastic oral spindle cell lesions.

Spindle cell lesions comprise a vast plethora of benign and malignant lesions with similar clinical and radiographic features. Their overlapping histopathologic features ensure a diagnostic dilemma. The current multicentric study aims to delineate fibroblastic and myofibroblastic oral spindle cell lesions based on cytomorphology and comprehensive immunohistochemical analysis. The experimental study was conducted at MS Ramaiah University of Applied Sciences, Bangalore, and All India Institute of Applied Sciences, Delhi. A comprehensive histological scoring criteria and panel of immunohistochemical makers (STAT6, CD31, CD34, S100, SMA, vimentin, pan-CK, HHF-35, Ki67, ALK, desmin, HMB-45, SATB2, ERG, EMA and CD99) were employed concurrently for the first time for fibroblastic and myofibroblastic oral spindle cell lesions. The data obtained was tabulated and studied. NA. Results: Using cytological scoring criteria and panel of immunohistochemical makers, the cases analysed and characterized were desmoplastic fibroma, fibrosarcoma, leiomyosarcoma, nodular fasciitis, neurofibroma and epithelioid inflammatory myofibroblastic sarcoma (EIMS). The diagnostic strategies need to be upgraded for the diagnosis of spindle cell lesions. Emphasis must be placed on cytomorphology, an immunohistochemistry (IHC) panel of markers is imperative for the accurate diagnosis of fibroblastic and myofibroblastic oral spindle cell lesions.

Hepatic Inflammatory Pseudotumor-Focusing on Its Heterogeneity.

Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells, hetorogenous populations of inflammatory cells, particularly plasma cells, lymphocytes and macrophages, as well as locations of fibrosis and necrosis without cellular anaplasia or atypical mitoses. Despite subsequent reports in the references, hepatic IPT remains difficult to diagnose; while posing major issues specifically for its differential diagnosis compared with that of other various benign diseases and malignant hepatic tumors. Histopathological findings are always a requisite for confirming the diagnosis, particularly given that the pathogenesis of IPT remains ambiguous to date. Hepatic IPT is a heterogeneous entity in terms of its clinical features, pathological findings, and pathogenesis. Once the diagnosis is confirmed, however, needless surgery such as wedge resection and lobectomy should be avoided. Here, we discuss the heterogeneity of hepatic IPT, its clinical features, pathological findings, and pathogenesis, and describe its differential diagnosis.

Difficulties in diagnosing a myofibroblastic lung tumor in a child

Inflammatory myofibroblastic tumor (VMO) is a rare neoplasm, which is currently referred to as a mesenchymal neoplasm with intermediate biological potential. The tumor consists of differentiated myofibroblastic fusiform cells. The frequency of occurrence of VMO among primary lung neoplasms is up to 1%. This type of tumor is the most common type of primary lung tumors in children. VMO can occur both in childhood and in adulthood. VMO is found in the soft tissues of the abdominal cavity, in the pelvic organs, larynx, mammary gland, head and neck tissues. Extra-organ localization (retroperitoneal space, mediastinum) is also diagnosed. Lung VMO often has no clinical manifestations, and if present has nonspecific symptoms, such as cough, hemoptysis, shortness of breath, hyperthermia, chest pain. VMO was previously considered as a neoplasm with a benign course, but these tumors tend to local relapses and distant metastasis. The article presents data on the prevalence, clinical manifestations and treatment of VMO, as well as own clinical observation of the course of this disease in an 8-year-old child.

Novel insights into biomarkers of progression in Desmoid tumor.

Desmoid tumor (DT) is a rare neoplasm characterized by the proliferation of myofibroblastic cells that infiltrates and invades adjacent tissues. Due to its locally aggressive and recurrent nature, DT often causes local symptoms and can be challenging to manage clinically. Therefore, identifying biomarkers that can predict the progression of DT and guide treatment decisions is critical. This review summarizes several biomarkers that have been implicated in active surveillance (AS) and the prediction of postoperative recurrence and attempts to elucidate their underlying mechanisms. Some of these novel markers could provide prognostic value for clinicians, and ultimately help facilitate optimal and accurate therapeutic decisions for DT.

#4286 ACCUMULATION OF MALADAPTIVE TUBULAR EPITHELIAL CELLS (TECS) IS UBIQUITOUS IN CKD AND REPRESENTS A COMMON INITIATING MECHANISM OF DISEASE PROGRESSION

Abstract Background and Aims Interstitial fibrosis, tubular atrophy and inflammation are common final pathways to end-stage kidney disease (ESKD), contributing to progressive nephron loss and functional decline in most chronic kidney diseases (CKD), including those considered to be glomerular in origin. Disease-associated maladaptive TECs have been described in rodent models1 and are characterized by a failed repair phenotype that contributes to tubulointerstitial fibrosis and inflammation. The contribution of equivalent maladaptive cell states to human CKD progression remains poorly described. The aim of this study was to characterize maladaptive TECs in the NURTuRE CKD cohort to assess their abundance and potential role in initiating inflammation and fibrosis in a large and heterogeneous patient population. Method Human maladaptive TECs were identified in an scRNA-Seq dataset (GSE171314) from IgA nephropathy patients by scoring cells with a TNF activation and a mouse proximal tubule failed repair (FR) gene signature[1]. The results were validated in a scRNA-Seq dataset (GSE171458) from patients with membranous nephropathy. Marker genes for these human maladaptive TEC clusters were derived using the Seurat R package and the top 50 candidates were combined into cell state-specific signatures. Single-sample signature scores were calculated for 310 kidney biopsy transcriptomes from various CKD etiologies in the NURTuRE cohort. Signature scores were correlated with eGFR and used in a time-to-event analysis (40% decline in eGFR or occurrence of ESRD) to predict renal event-free survival. Results Analysis of independent human scRNA-Seq datasets and scoring with TNF activation and mouse proximal tubule FR gene signatures revealed two distinct maladaptive TEC states associated with different tubular segments. A cluster of cells (FR-PT) with increased TNF activation and mouse FR signature expression were identified that clustered adjacent to proximal TECs, suggesting a lineage relationship. A second cluster of cells (DT2) with increased TNF activation was clustered adjacent to thick ascending limb (TAL) cells, suggesting distal tubule lineage. Both maladaptive TEC clusters were detected at low levels in healthy controls but increased in CKD. FR-PT and DT2 cells are characterized by a pro-fibrotic and pro-inflammatory gene expression and likely represent a source of signalling molecules mediating stromal crosstalk in the kidney fibrotic microenvironment. To investigate their abundance in CKD, signature expression in NURTuRE kidney biopsy transcriptomes was summarized into a sample-level score. Signature scores for FR-PT and DT2 cells were generally elevated in all CKD etiologies with substantial variation within disease groups. Inverse correlation of eGFR with the scores suggested an accumulation of maladaptive TECs with kidney function decline, largely independent of primary diagnosis (Fig. 1). Pseudotime analysis revealed that this accumulation accompanied or preceded increases in myofibroblast and immune cell gene expression, suggesting a mechanism that may be driving disease initiation and progression. Importantly, high expression of the FR and DT2 signatures was associated with a decrease in renal event-free survival (Fig. 2), further supporting their relevance to human disease progression. Conclusion This study suggests an important role for an accumulation of maladaptive TECs in CKD progression. These cells are observed in every CKD etiology that was included in this study, suggesting that targeting these cells could be an effective strategy to preserve kidney function broadly in CKD. Identification of surrogate blood or urine biomarker would allow for the identification of patients with increased levels of these cells regardless of disease etiology.

Cell surface ATP synthase-released H+ and ATP play key roles in cocoa butter intake-mediated regulation of gut immunity through releases of cytokines in rat.

Proper food intake is important for maintaining good health in humans. Chocolate is known to exert anti-inflammatory effects; however, the mechanisms remain unclear. In this study, we aimed to investigate the effects of cocoa butter intake on gut immunity in rats and rabbits. Cocoa butter intake increased the lymph flow, cell density, and IL-1β, IL-6 and IL-10 levels in mesenteric lymph. Clodronate, a macrophage depletion compound, significantly enhanced the release of all cytokines. The immunoreactivities of macrophage markers CD68 and F4/80 in the jejunal villi were significantly decreased with clodronate. Piceatannol, a selective cell surface ATP synthase inhibitor significantly reduced the cocoa butter intake-mediated releases of IL-1β, IL-6 and IL-10. The immunoreactivities of cell surface ATP synthase were observed in rat jejunal villi. Shear stress stimulation on the myofibroblast cells isolated from rat jejunum released ATP and carbon dioxide depended with H+ release. In rabbit in vivo experiments, cocoa butter intake increased the concentrations of ATP and H+ in the portal vein. The in vitro experiments with isolated cells of rat jejunal lamina propria the pH of 3.0 and 5.0 in the medium released significantly IL-1β and IL-6. ATP selectively released IL-10. These findings suggest that cocoa butter intake regulates the gut immunity through the release and transport of IL-1β, IL-6, and IL-10 into mesenteric lymph vessels in a negative feedback system. In addition, the H+ and ATP released from cell surface ATP synthase in jejunal villi play key roles in the cocoa butter intake-mediated regulation of gut immunity.

Understanding of arthrofibrosis: New explorative insights into extracellular matrix remodeling of synovial fibroblasts.

Arthrofibrosis following total knee arthroplasty is a fibroproliferative joint disorder marked by dysregulated biosynthesis of extracellular matrix proteins, such as collagens and proteoglycans. The underlying cellular events remain incompletely understood. Myofibroblasts are highly contractile matrix-producing cells characterized by increased alpha-smooth muscle actin expression and xylosyltransferase-I (XT-I) secretion. Human XT-I has been identified as a key mediator of arthrofibrotic remodeling. Primary fibroblasts from patients with arthrofibrosis provide a useful in vitro model to identify and characterize disease regulators and potential therapeutic targets. This study aims at characterizing primary synovial fibroblasts from arthrofibrotic tissues (AFib) regarding their molecular and cellular phenotype by utilizing myofibroblast cell culture models. Compared to synovial control fibroblasts (CF), AFib are marked by enhanced cell contractility and a higher XT secretion rate, demonstrating an increased fibroblast-to-myofibroblast transition rate during arthrofibrosis. Histochemical assays and quantitative gene expression analysis confirmed higher collagen and proteoglycan expression and accumulation in AFib compared to CF. Furthermore, fibrosis-based gene expression profiling identified novel modifier genes in the context of arthrofibrosis remodeling. In summary, this study revealed a unique profibrotic phenotype in AFib that resembles some traits of other fibroproliferative diseases and can be used for the future development of therapeutic interventions.

Morphological variations of two cases of maxillary myofibromas

The aim of this case report is to depict the varied spectrum of clinical presentation of two cases of solitary myofibromas, one of which was intra-osseous whilst the other presented as a soft tissue lesion. This highlights the spectrum of the clinical presentation of the same pathology. In the most recent World Health Organisation (WHO) 2022 classification of soft tissue tumours, myofibroma is included under the category of myopericytomas. Myopericytoma is a distinctive perivascular myoid neoplasm that forms a morphological spectrum with myofibroma. Molecular evidence has revealed PDGFRB (platelet-derived growth factor receptor beta) mutations in myopericytoma and myofibroma as well as SRF-RELA gene fusions in both lesions confirming a common pathogenesis for both.1 Myofibromas are benign soft tissue neoplasms derived from myofibroblastic cells.2 The term myofibroma refers to a solitary lesion. Myofibromatosis refers to cases in which multiple lesions are present which may affect either one or multiple anatomical locations. Myofibromatosis is almost exclusively seen in young children under the age of 2-years. Myofibromas exhibit a wide age range of clinical presentation and may be present at birth or arise within the first two years of age, but may also present in adults with a significant male predominance. Solitary myofibromas have a predilection to occur in the oral cavity, skin or subcutis of the head, neck and trunk.

FAPI PET Signal in Hibernoma Reflects FAP Expression in Tumor Vasculature Cells.

A 43-year-old man with a growing mass in the right groin, concerned for liposarcoma, underwent MRI and 68Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT before surgery. Fibroblast activation protein inhibitor PET/CT demonstrated increased uptake (SUVmax, 3.2) predominantly in the solid portion, where MRI showed gadolinium enhancement. The patient subsequently underwent surgery and was diagnosed with hibernoma. The immunohistochemistry of the tumor revealed the fibroblast activation protein expression in the fibrovascular network and myofibroblastic cells of the tumor. This case suggests that the FAPI uptake can be affected by the vascular cells, and thus, a careful interpretation of the FAPI PET signal may be needed.