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In vitro models serve as valuable tools for understanding the complex cellular and molecular interactions involved in granuloma formation, providing a controlled environment to explore the underlying mechanisms of their development and function. Various models have been developed to replicate granulomatous diseases, even though they may lack the sophistication needed to fully capture the variability present in clinical spectra and environmental influences. Traditional cultures of PBMCs have been widely used to generate granuloma models, enabling the study of aggregation responses to various stimuli. However, growing cells on a two-dimensional (2D) plastic surface as a monolayer can lead to altered cellular responses and the modulation of signaling pathways, which may not accurately represent in vivo conditions. In response to these limitations, the past decade has seen significant advancements in the development of three-dimensional (3D) in vitro models, which more effectively mimic in vivo conditions and provide better insights into cell–cell and cell–microenvironment interactions. Meanwhile, the use of in vivo animal models in biomedical research must adhere to the principle of the three Rs (replacement, reduction, and refinement) while ensuring that the models faithfully replicate human-specific processes. This review summarizes and compares the main models developed to investigate granulomas, focusing on their contribution to advancing our understanding of granuloma biology. We also discuss the strengths and limitations of each model, offering insights into their biological relevance and practical applications. [ABSTRACT FROM AUTHOR]

Cherubism is a rare genetic disorder caused by SH3BP2 mutations. This sterile autoinflammatory disease is characterized by jaw osteolysis, in which bone tissue is replaced by multinucleated giant cells containing fibrous tissue. The cherubism mouse model (Sh3bp2 KI) is characterized by systemic bone loss as well as inflammatory phenotypes induced and maintained by TNFα. IL-1β, produced by the NRLP3 inflammasome through recruitment of Caspase-1, is involved in the development of sterile autoinflammatory disease. We previously reported a cherubism patient with elevated serum IL-1β, and cherubism mice also have elevated serum IL-1β levels. Thus, we wanted to disentangle the role of IL-1β in cherubism. To that end, we deleted Caspase-1 in Sh3bp2 KI mice to tamp down IL-1β production. However, deleting Caspase-1 did not rescue the systemic bone and inflammatory phenotypes. [ABSTRACT FROM AUTHOR]

AbstractPerivascular epithelioid cell tumors (PEComas) of the kidney are rare mesenchymal tumors that rarely occur in children. Individuals with tuberous sclerosis (TS) are at increased risk for these tumors. While classic PEComas are benign, the epithelioid variant could have malignant potential and metastasis capacity. We report a case of right kidney epithelioid PEComa with uncertain malignant potential in a 3-year-old girl who had no personal or family history of tuberous sclerosis. The tumor was found through ultrasound imaging. Sections from the radical nephrectomy specimen showed epithelioid and spindle cells with abundant granular eosinophilic or clear cytoplasm, mildly pleomorphic vesicular nuclei and distinctive perivascular arrangement. Abundant multinucleated giant cells were seen. No further therapy was suggested by the oncologist. The patient is doing well ten months post-surgery. We reviewed the literature and analyzed the features of pediatric renal PEComas reported so far. [ABSTRACT FROM AUTHOR]

The article discusses a rare case of an extramedullary surface-based chondroblastoma in a young adult with left knee pain. Chondroblastoma is a benign but locally aggressive cartilage-forming tumor typically found in the epiphysis of long bones in skeletally immature patients. The case presented in the article adds to the limited literature on this unique entity, emphasizing the importance of considering periosteal chondroblastoma in the differential diagnosis of surface tumors in young patients. Treatment involves thorough surgical excision or curettage, with a generally favorable prognosis after complete removal. [Extracted from the article]

Background: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Case Presentation: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. Discussion: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. Conclusion: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection. [ABSTRACT FROM AUTHOR]

Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B. pseudomallei strains, variants of hcp1 have recently been identified. This study aimed to examine the prevalence of hcp1 variants in clinical isolates of B. pseudomallei, assess the antigenicity of the Hcp1 variants, and the ability of strains expressing these variants to stimulate multinucleated giant cell (MNGC) formation in comparison to strains expressing wild-type Hcp1 (Hcp1wt). Sequence analysis of 1,283 primary clinical isolates of B. pseudomallei demonstrated the presence of 8 hcp1 alleles encoding three types of Hcp1 proteins, including Hcp1wt (98.05%), Hcp1variant A (1.87%) and Hcp1variant B (0.08%). Compared to strains expressing Hcp1wt, those expressing the dominant variant, Hcp1variant A, stimulated lower levels of Hcp1variant A-specific antibody responses in melioidosis patients. Interestingly, when Hcp1variant A was expressed in B. pseudomallei K96243, this strain retained the ability to stimulate MNGC formation in A549 cells. In contrast, however, similar experiments with the Hcp1variant B demonstrated a decreased ability of B. pseudomallei to stimulate MNGC formation. Collectively, these results show that B. pseudomallei strains expressing variants of Hcp1 elicit variable antibody responses in melioidosis patients and differ in their ability to promote MNGC formation in cell culture. Author summary: Hcp1 is a component of the virulence-associated Type VI Secretion System 1 (T6SS1) that plays a significant role in the MNGC formation of B. pseudomallei in hosts. In addition to its importance in bacterial pathogenesis, Hcp1 is recognized by the host immune system, resulting in strong antigen-specific humoral and cellular responses in melioidosis patients and protective immunity in animal models. Our analysis of hcp1 sequences from 1,283 clinical B. pseudomallei isolates revealed genetic diversity and identified 8 hcp1 alleles and 3 types of Hcp1. We demonstrated that Hcp1variant A, associated with several amino acid changes, could still function in cell-to-cell spread similar to Hcp1wt, but it exhibited decreased specific antibody levels in plasma of melioidosis patients compared to the levels stimulated by Hcp1wt. Understanding the impact of possible antigenic variation with respect to immune responses and bacterial pathogenesis will be necessary to determine if expression of different Hcp1 proteins may have implications for the development of effective treatments and vaccines. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 6-month-old infant presenting with acute respiratory failure due to CD40L deficiency, a rare inborn error of immunity. The patient's symptoms did not respond to typical treatments, leading to further investigations that revealed the underlying condition. CD40L deficiency can present with various clinical manifestations, including pulmonary, gastrointestinal, infectious, autoimmune, lymphoproliferation, and malignant etiologies. Early management with IVIG and antibiotic prophylaxis can help reduce life-threatening infections, and a hematopoietic stem cell transplant (HSCT) is curative. [Extracted from the article]

Abstract Cell–cell fusion is a vital biological process where the membranes of two or more cells merge to form a syncytium. This phenomenon is critical in various physiological and pathological contexts, including embryonic development, tissue repair, immune responses, and the progression of several diseases. Osteoclasts, which are cells from the monocyte/macrophage lineage responsible for bone resorption, have enhanced functionality due to cell fusion. Additionally, other multinucleated giant cells (MGCs) also arise from the fusion of monocytes and macrophages, typically during chronic inflammation and reactions to foreign materials such as prostheses or medical devices. Foreign body giant cells (FBGCs) and Langhans giant cells (LGCs) emerge only under pathological conditions and are involved in phagocytosis, antigen presentation, and the secretion of inflammatory mediators. This review provides a comprehensive overview of the mechanisms underlying the formation of multinucleated cells, with a particular emphasis on macrophages and osteoclasts. Elucidating the intracellular structures, signaling cascades, and fusion-mediating proteins involved in cell–cell fusion enhances our understanding of this fundamental biological process and helps identify potential therapeutic targets for disorders mediated by cell fusion.

Abstract Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.

Background: Dermal fillers such as hyaluronic acid (HA) have been widely used in recent years as a less surgically invasive cosmetic treatment. Although delayed foreign body granuloma may occur as a rare adverse reaction after the procedure, detailed histological reports are still limited. When occurring on the buccal mucosa of the oral cavity, the histopathology may resemble some lesions of minor salivary gland origin due to the material properties of HA. Here we report a delayed foreign body granuloma associated with HA showing eosinophilic infiltration of the buccal mucosa, with characteristic histological and immunohistological features. Case Presentation: A 61‐year‐old woman presented with swelling and a burning sensation in the right buccal mucosa. On initial examination, a 25 × 20‐mm mass was palpated on the anterior margin of the right masseter muscle. Examination of a biopsy specimen revealed multiple pseudoduct‐like structures containing mucoid substance within the mucosal lamina propria. The mucoid substance was positively stained with Alcian blue (AB) and surrounded by CD68‐positive epithelioid cells and multinucleated giant cells. Many histiocytes had infiltrated into the surrounding area, and numerous eosinophilic infiltrates were also evident. After a review of the patient's history, a diagnosis of delayed foreign body granuloma associated with HA injection was made. Conclusion: We have reported a case of delayed foreign body granuloma with eosinophilic and histiocytic infiltration following injection of HA. It was suggested that the marked eosinophilic infiltration around macrophages was due to not only an allergic reaction, but also in part to increased macrophage aggregation. [ABSTRACT FROM AUTHOR]

The article discusses keratin-positive giant cell tumors of bone and soft tissue in children under 10 with HMGA2::NCOR2 fusion, focusing on three cases. The tumors are classified based on molecular alterations, with HMGA2::NCOR2 fusions distinguishing them from other giant cell-rich tumors. The youngest patient, a neonate with metastatic disease, showed a remarkable response to imatinib therapy. The study expands the understanding of these tumors and their response to targeted therapy, highlighting the importance of molecular characterization in diagnosis and treatment. [Extracted from the article]

Objectives We sought to investigate the clinicopathologic features and differential diagnosis of plexiform fibrohistiocytic tumor (PFHT) and its pathogenesis. Methods Ten cases of PFHT were collected from Xi Jing Hospital, Fourth Military Medical University, from September 2008 to December 2022 for clinical data as well as microscopic and immunohistochemical observation. CCND1 gene amplification and break were assayed by fluorescence in situ hybridization (FISH). Results We report 10 cases of PFHT according to histologic classification. Seven cases were of histiocytoid type, and 3 had mucous degeneration in the nodules. One case was of fibroblastic type, which was mainly composed of fibroblast-like cells. Two cases were of mixed type. Immunohistochemically, the osteoclast-like multinucleated giant cells, histiocyte-like cells, and occasional spindle cells in the adjacent fascicles were reactive for CD68 (10/10), CD163 (5/8), CD10 (8/8), cyclin D1 (8/8), CDK4 (5/8), β-catenin (4/6), MITF (2/6), and PGP9.5 (4/5). Vimentin (9/9) was strongly positive in tumor cells and peripheral fibroblast-like cells. The positive index of Ki-67 was 5% to 40%, with an average of 20%. The FISH analysis showed neither amplification nor break of the CCND1 gene. All cases underwent surgical resection, and patients were followed up for 9 months to 11 years. Only 2 cases recurred. Conclusions Plexiform fibrohistiocytic tumor is a low-grade malignant soft tissue neoplasm. The diagnosis mainly depends on histopathologic and immunohistochemical markers. Cyclin D1 and CD10 expression has diagnostic value for the diagnosis and differential diagnosis of PFHT combined with its plexiform morphology. The overexpression of cyclin D1 suggests an involvement of cell cycle regulatory genes in the pathogenesis of PFHT. [ABSTRACT FROM AUTHOR]

Bone is a dynamic organ which continuously undergoes remodeling throughout one's lifetime. Cellular production of reactive oxygen species (ROS) is essential for regulating bone homeostasis. Osteoclasts, multinucleated giant cells differentiated from macrophage lineage, are responsible for osteolytic bone conditions which are closely linked to ROS signaling pathways. In this study, an anti‐ROS enzyme, peroxiredoxin 1 (Prdx1) was found to be expressed both in bone marrow macrophages and osteoclasts. Recombinant Prdx1 protein was found to dose‐dependently inhibit ROS production and osteoclast differentiation. Mechanistically, Prdx1 protein also attenuated NFATc1 activation as well as the expression of C‐Fos, V‐ATPase‐d2, Cathepsin K, and Integrin αV. Collectively, Prdx1 is a negative regulator on osteoclast formation via inhibiting RANKL‐mediated ROS activity, thus suggesting its potential application for treating osteoclast related disorders. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive soft tissue sarcoma with a poor prognosis. The patients are usually found to have metastasis when the primary tumor is diagnosed. Eccrine syringofibroadenoma (ESFA) is a rare cutaneous adnexal lesion of eccrine duct origin. There are five subtypes, one of which is reactive ESFA, known to occur in reaction to an inflammatory or neoplastic process. In this article, we report a case of the co-existence of both UPS and ESFA in a 70-year-old male patient, presenting with a painless, erythematous, irregular surface nodule with a peripherally extended brownish hyperkeratotic plaque on the right palm. The histologic findings revealed an ill-defined dermal tumor of atypical epithelioid and spindle-shaped cells with large pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm. Some of those cells were multinucleated giant cells in the stroma with vascular proliferation and mixed inflammatory cell infiltrate. The tumor cells, which were only positive for vimentin, supported the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Meanwhile, the overlying epidermis demonstrated hyperkeratosis, papillated epidermal hyperplasia, and proliferation of anastomosing slender cords and strands of cuboid cells within loose fibrovascular stroma. These findings are the characteristics of eccrine syringofibroadenoma (ESFA). We describe here a patient in whom reactive ESFA occurred on and surrounded the UPS tumor. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a leading infectious disease with varied manifestations. We report a rare presentation of gastric TB in a 50-year-old immunocompetent woman from the Middle East with no prior medical history. The patient presented with persistent epigastric pain, weight loss, nausea, and vomiting over a 2-month duration. Imaging studies and an infectious disease panel were inconclusive. However, upper endoscopy revealed a subepithelial lesion at the pylorus, with biopsies demonstrating caseating granuloma and multinucleated giant cells. A QuantiFERON test was subsequently positive for TB. The patient was successfully treated with standard TB quadruple therapy, resulting in significant improvement in symptoms during follow-up. This case underscores the importance of considering extrapulmonary TB in immunocompetent patients with atypical gastrointestinal symptoms and highlights the efficacy of prompt antitubercular therapy. [ABSTRACT FROM AUTHOR]

Osteoclasts are bone-resorbing multinucleated giant cells formed by the fusion of monocyte/macrophage lineages. Various small GTPases are involved in the multinucleation and differentiation of osteoclasts. However, the roles of small GTPases regulatory molecules in osteoclast differentiation remain unclear. In the present study, we examined the role of Dennd2c, a putative guanine nucleotide exchange factor for Rab GTPases, in osteoclast differentiation. Knockdown of Dennd2c promoted osteoclast differentiation, resorption, and expression of osteoclast markers. Morphologically, Dennd2c knockdown induced the formation of larger osteoclasts with several protrusions. In contrast, overexpression of Dennd2c inhibited the multinucleation and differentiation of osteoclasts, bone resorption, and the expression of osteoclast markers. Dennd2c-overexpressing macrophages exhibited spindle-shaped mononuclear cells and long thin protrusions. Treatment of Dennd2c-overexpressing cells with the Cdc42 inhibitor ML-141 or the Rac1 inhibitor 6-thio-GTP prevented protrusion formation. Moreover, treatment of Dennd2c-overexpressing cells with the actin polymerization inhibitor latrunculin B restored multinucleated and TRAP-positive osteoclast formation. These results indicate that Dennd2c negatively regulates osteoclast differentiation and multinucleation by modulating protrusion formation in macrophages. [ABSTRACT FROM AUTHOR]

Phthalates are a group of chemicals used to make plastics more durable, and they are often called plasticisers. Additionally, these chemicals are found in hundreds of products such as floor coverings, lubricating oils, and personal care products (soaps, shampoos, hair sprays). Consumer products containing phthalates can result in human exposure through direct contact and use, indirectly through leaching into the other products or general environmental contamination. In this study, the effects of Diisobutyl phthalate a commonly used phthalate, were investigated histopathologically and morphometrically to determine whether it is one of the causes of increased infertility in recent years. Two study groups of albino Wistar albino rats (total n: 40) were formed; the control group (untreated control group, solvent-corn oil the control group) and the experimental group. DiBP was administered by oral gavage to the experimental group in 3 different doses (0.25--0.5--1 mL/kg/day) mixed with corn oil every day for 28 days. At the end of the experiment, testicular tissue samples taken from all the experimental and control animals were evaluated histopathologically and morphometrically by light microscopy after routine preparation. Degeneration/atrophic tubules were quite prominent in the sections. Tubules containing degenerated germ cells and tubules devoid of germ cells were observed. It was determined that in most tubules, only tubules covered with Sertoli cells remained due to germ cell death. In addition, multinucleated giant cells were frequently encountered in such tubules. Dilatation and thickening in the basal lamina of the seminiferous tubule were accompanied by decreased PAS-positive reaction. The morphometric results supported the histopathological findings. Significant dose-related morphometrical changes (p<0.0001), including seminiferous tubule diameter, tubular lumen diameter, spermatogenic cell line height and basal lamina thickness were observed between the control and administration groups. According to the control, sham and G1, the number of these multinucleated cells (MGC) increased in G2 and G3 but these increases were statistically insignificant (p > 0.9999). In conclusion, it was observed that irreversible damage occurred in the testicular tissues of DiBP-exposed groups, and it was decided that this could be the cause of infertility. Therefore, we recommend the use of an alternative plasticiser with proven reliability. [ABSTRACT FROM AUTHOR]

Background/Objectives: Myocarditis is an inflammatory disease of the myocardium and remains to this day a challenging diagnosis. A promising novel imaging method uses the expression of somatostatin receptors (SSTRs) on inflammatory cells to visualize myocardial inflammation. However, little is known about the histopathological correlate of SSTR imaging in different forms of myocarditis. Methods: In the present retrospective histopathological study, we systematically analysed the expression of SSTR subtype 2 (SSTR2) on inflammatory cells of 33 patients with biopsy- or explant-proven myocarditis (lymphocytic myocarditis (n = 5), giant-cell myocarditis (n = 11), and cardiac sarcoidosis (n = 17)), and in eight controls (multi-organ donors) without signs of myocardial inflammation and/or scars. Results: In all patients, immunohistochemical staining for SSTR2 was positive in areas with CD68-positive macrophages and multinucleated giant cells. Staining for SSTR2 was most prominent in the presence of multinucleated giant cells. The colocalization of both SSTR2 and CD68 on the same cell could be confirmed using immunofluorescence microscopy. Western blotting confirmed the upregulated expression of SSTR2 in cases of granulomatous inflammation (sarcoidosis) of the skeletal and heart muscle, in comparison with controls. Conclusions: In conclusion, our findings demonstrate the expression of SSTR2 on the protein level on CD68-positive macrophages and multinucleated giant cells in various forms of myocarditis, which provides a clear rationale for the diagnostic use of SSTR imaging in this patient group. [ABSTRACT FROM AUTHOR]

Purpose: To study the morphological and histological characteristics of the fibrous capsule formed around a novel biodegradable glaucoma drainage device (GDD) implant made of oxidized regenerated cellulose (ORC) after 1 and 3 months of its implantation. Methods: It was a prospective, interventional, preclinical experimental study using New Zealand white rabbits. All animals underwent GDD implantation with a novel biodegradable device. The device's body was made of ORC and attached to a silicone tube, connecting the body to the anterior chamber. Histopathology (hematoxylin and eosin/Masson's trichrome staining) and immunohistochemistry (Alpha-Smooth Muscle Actin expression) characteristics of the bleb formed around the novel device were noted at 1 and 3 months. Results: One month post implantation, the biodegradable material produced a significant foreign body type of reaction evidenced by the exuberant infiltration by macrophages, lymphocytes, and multinucleated giant cells. The granulomatous response subsided by 3 months with disorganized collagen deposition on Masson's trichrome staining. The silicone tube was an internal control, and histopathology demonstrated well-organized collagen deposition around it at 3 months. Immunohistochemistry for α-smooth muscle actin also demonstrated more myofibroblast transformation at the site of the tube than the biodegradable implant. Conclusions: Our results indicate that the tissue response around a biodegradable GDD was different from the response to conventional devices. A diffuse, loose vascularized mesh was observed to develop, which may be more compatible with sustained IOP control over a longer period, in contrast to the usual thick and dense capsule formed around the non-biodegradable devices. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusion Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra‐alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear‐resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease.We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs.These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism. [ABSTRACT FROM AUTHOR]

The article "Unveiling the Mechanism: Injectable Poly-L-Lactic Acid's Evolving Role—Insights From Recent Studies" in the Journal of Cosmetic Dermatology delves into the use of Sculptra poly-L-lactic acid in aesthetic dermatology to address volume loss, skin laxity, and wrinkles. It examines how PLLA stimulates collagen production, triggers adipogenesis, and promotes new extracellular matrix formation, potentially increasing volume in treated areas. The research suggests a complex relationship between PLLA, fibroblasts, macrophages, and adipocytes in achieving desired aesthetic outcomes, with unanswered questions remaining about PLLA's cell recognition mechanism. Further studies are needed to comprehend PLLA's effects on adipogenesis, immunological responses, angiogenesis, and interactions with other cells. The study was funded by Galderma, and the data are publicly accessible on PubMed. [Extracted from the article]

ABSTRACT Objective Materials and Methods Results Conclusion To analyze the characteristics of a series of oral reactions to injectable soft tissue fillers.Cases diagnosed as oral reactions to injectable soft tissue fillers were selected from eight Pathology laboratories. Information was retrieved from the laboratory charts and from the review of the hematoxylin and eosin‐stained histological slides.The 151 patients showed a mean age of 54.9 years, and 136 (90.1%) were females. Mean time of onset was 20.4 months, and the lips were the most frequent location (72.8%). Most cases presented as asymptomatic isolated nodules, with a mean size of 17.4 mm. Silicone (38.5%), polymethylmetacrylate (33%), and hyaluronic acid (11.9%) were the three most common fillers. Granulomas, foamy macrophages, and multinucleated giant cells were observed in 44%, 51.5%, and 65.3% of the cases, respectively. Time of onset was shorter for males (p = 0.033), and symptoms were common in the upper lip, buccal mucosa, and lower vestibule (p = 0.010). Foamy macrophages were more common in association with silicone and collagen (p < 0.001), whereas multinucleated giant cells were more common in association with polymethylmetacrylate, hydroxiapatite, and polylactic acid (p = 0.012).Clinicians should consider reactions to injectable soft tissue fillers when evaluating asymptomatic submucosal nodules affecting the lips of adult/older females. [ABSTRACT FROM AUTHOR]

This article discusses two cases of severe hypercalcemia in lung transplant recipients, which were diagnosed as Pneumocystis jirovecii pneumonia (PJP). Both patients were successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) and showed improvement in symptoms and calcium levels. The article highlights the importance of considering PJP as a possible cause of hypercalcemia in immunocompromised patients and suggests further research on risk factors and prophylaxis strategies. [Extracted from the article]

Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility. [ABSTRACT FROM AUTHOR]

The article discusses a case of erythema nodosum (EN) induced by a tumor necrosis factor‐alpha (TNF‐α) inhibitor in a 60‐year‐old female patient with peripheral spondyloarthritis. The patient developed painful nodules on her legs after treatment with adalimumab and later etanercept. The article provides a comprehensive literature review of similar cases and highlights the importance of considering EN as a potential side effect of anti‐TNF therapy. The authors emphasize the need for a thorough diagnostic workup to rule out other causes of EN and suggest collaborative management with a dermatologist while maintaining anti‐TNF therapy if it effectively controls the underlying autoimmune condition. [Extracted from the article]

Primary breast osteosarcomas are rare. We report an unusual case of a 58-year-old female presenting with a right breast lump for 1 month. Mammography showed an ill-defined, heterogeneous, and coarse calcification measuring 4 cm over the upper inner quadrant of the right breast. She received an upfront partial mastectomy after core needle biopsy showed osteoid-like tissue with the presence of atypical cells and some multinucleated giant cells. The final pathology revealed Grade 3 extraosseous osteosarcoma, osteoblastic type. Four cycles of adjuvant doxorubicin and cisplatin followed by radiotherapy were given due to the close surgical margin. She has since been free of recurrence for 3 years. [ABSTRACT FROM AUTHOR]

HIV establishes long-term latent infection in memory CD4+ T cells and also establishes sustained long-term productive infection in macrophages, especially in the central nervous system (CNS). To better understand how HIV sustains infection in macrophages, we performed RNAseq analysis after infection of human monocytederived macrophages (MDMs) with the brain-derived HIV-1 strain YU2 and compared this with acute infection of CD4+ T cells. HIV infection in MDM and CD4+ T cells altered many gene transcripts, but with few overlaps between these different cell types. We found interferon pathways upregulated in both MDM and CD4+ T cells, but with different gene signatures. The interferon-stimulated gene RSAD2/Viperin was among the most upregulated genes following HIV infection in MDMs, but not in CD4+ T cells. RSAD2/Viperin was induced early after infection with various HIV strains, was sustained over time, and remained elevated in established MDM infection even if new rounds of infection were blocked by antiretroviral treatment. Immunofluorescence microscopy revealed that RSAD2/Viperin was induced in HIV-infected cells, as well as in some uninfected neighboring cells. Knockdown of RSAD2/Viperin following the establishment of infection in MDMs reduced the production of HIV transcripts and viral p24 antigen. This correlated with the reduction in the number of multinucleated giant cells, and changes in the HIV DNA and chromatin structure, including an increased DNA copy number and loss of nucleosomes and histone modifications at the long terminal repeat (LTR). RNAseq transcriptomic analysis of RSAD2/Viperin knockdown during HIV infection of MDMs revealed the activation of interferon alpha/beta and gamma pathways and the inactivation of Rho GTPase pathways. Taken together, these results suggest that RSAD2/Viperin supports the sustained infection in macrophages, potentially through mechanisms involving the alteration of the LTR chromatin structure and the interferon response. [ABSTRACT FROM AUTHOR]

A 4-year 9-month-old Amami spiny rat reared in a zoo died following a history of anorexia, weight loss, and respiratory distress. At necropsy, neoplastic tissues were found along the pleura and adhered to the thoracic wall, heart, and lungs. Histologically, the tumor was composed of diffuse, patternless sheets of large round to polygonal neoplastic cells with abundant eosinophilic cytoplasm, and multinucleated giant cells were often present. Metastatic lesions were observed in the abdominal lymph nodes. Neoplastic cells were immunopositive for vimentin, Iba-1, and CD204, and negative for E-cadherin and S100. Based on these findings, the tumor was diagnosed as histiocytic sarcoma. Compression of the lungs by the tumor may have caused respiratory failure and led to death. [ABSTRACT FROM AUTHOR]

A 56-year-old woman presented with evolving lesions on the dorsal hands, diagnosed as multinucleate angiohistiocytoma, a rare benign vascular proliferation. The condition predominantly affects women aged 45-65 and may be underrecognized due to subtle histological features. Treatment options are limited, with trials of corticosteroids, surgical excision, and laser therapy showing limited success. This case highlights the appearance of multinucleate angiohistiocytoma in a patient with Fitzpatrick type VI skin, with differential diagnoses including dermatofibroma, Kaposi sarcoma, and lichen planus. [Extracted from the article]

The article discusses a case study of an 89-year-old woman with erythematous plaques and cervical lymphadenopathy, ultimately diagnosed with cutaneous tuberculosis - scrofuloderma. The patient's clinical and histopathological findings, differential diagnoses, and treatment plan are detailed, emphasizing the challenges of achieving a definitive microbiological diagnosis. The article highlights the importance of recognizing various presentations of cutaneous TB and treating based on characteristic clinical and histological findings in a high-risk context. [Extracted from the article]

The article in the Oman Journal of Ophthalmology discusses the case of an 11-month-old infant girl with unusual iris lesions in her left eye. The child was diagnosed with juvenile xanthogranuloma (JXG) and treated with steroid eye drops, resulting in a significant improvement and complete resolution of the lesions. JXG is a rare non-Langerhans cell histiocytosis that typically presents with yellow skin papules and can involve the eyes, requiring careful monitoring and treatment to prevent vision impairment. The article emphasizes the importance of timely identification and appropriate management of ocular JXG to ensure optimal outcomes for affected children. [Extracted from the article]

The article discusses a case report of a 48-year-old businessman with an atypical presentation of adult-onset hydroa vacciniforme, a rare photo-dermatosis. The patient experienced recurrent itchy skin eruptions in sun-exposed areas, leading to hypertrophic scars. Diagnosis was confirmed through histopathological examination and direct immunofluorescence (DIF) positivity. Treatment involved sun protection, hydroxychloroquine, and beta-carotene supplementation. The case underscores the importance of considering hydroa vacciniforme in adults with vesiculobullous eruptions on sun-exposed skin for early diagnosis and management. [Extracted from the article]

The article discusses a case of a 27-year-old male with lepromatous leprosy and chronic type 2 lepra reaction who developed cryptococcosis involving the skin and bone. The patient had received multiple courses of systemic steroids and other medications for the lepra reaction. Treatment with antifungal medications led to the healing of the skin lesions. The case highlights the importance of considering cryptococcosis in leprosy patients on immunosuppressive therapy to prevent serious complications. [Extracted from the article]

A 53-year-old woman with a 16-year history of epilepsy underwent microsurgical tumor resection for a mass in her left temporal lobe. The tumor was identified as a Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters. This rare entity predominantly affects pediatric patients but can also occur in older individuals, with distinct radiological and histopathological characteristics. Patients with this tumor generally have a favorable prognosis following surgical resection, although larger studies are needed to further understand these rare tumors. [Extracted from the article]

The presence of fungi in tracheal wash (TW) of horses was recently linked to mild-moderate equine asthma, indicating a possible causal role; however, increased numbers of fungi may also stem from asthma-related alteration of tracheal mucus clearance or from environmental exposure. Our objective was to elucidate the association between the presence of fungi in TW and asthma status while controlling for relevant confounders. We conducted a retrospective case-control study involving 73 horses, including 34 controls and 39 asthmatic cases. Each asthmatic horse was matched with a control from the same barn to account for the influence of environmental exposure. All horses underwent respiratory clinical scoring, endoscopy, TW, and bronchoalveolar lavage (BAL). The association between asthma status and presence of TW fungi was tested with multivariable logistic regression modelling, accounting for selected management factors, tracheal mucus accumulation, and selected TW and BAL cytological characteristics, including multinucleated giant cells (MGCs) in the TW. Given the variability in MGC definitions in the literature, particularly concerning their morphology and number of nuclei, we constructed two distinct models for each outcome (asthma status or presence of fungi in TW): one considering MGCs as cells with ≥ 3 nuclei, and another using a criterion of ≥ 10 nuclei. Horses with a tracheal mucus score ≥ 2 exhibited 3.6 to 4.3 higher odds of being asthmatic, depending on the MGC definition. None of the other variables examined were associated with either asthma status or TW fungi detection. Notably, the presence of fungal elements in the TW was not associated with equine asthma. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by systemic fibro-inflammatory infiltrates and an unfavorable prognosis. The disease has gained increasing interest due to a rise in cases, and consensus guidelines for diagnosis and management have been developed. ECD is generally diagnosed in middle-aged adults, with a higher incidence in males. Diagnostic challenges arise due to the variety of clinical manifestations and the need for differential diagnosis with other conditions such as idiopathic retroperitoneal fibrosis and chronic recurrent multifocal osteomyelitis. Thorough assessment and biopsy of fibrous tissue are recommended for accurate diagnosis and targeted genetic therapies. [Extracted from the article]

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity. [ABSTRACT FROM AUTHOR]

Simple Summary: Aspergillosis is an important fungal disease occurring in avian fauna, especially in birds kept in captivity. In Psittaciformes, severe disease occurs in the lungs and air sacs, with the development of white-to-yellow caseous nodules and plaques in the organs, in addition to greenish-grey fungal growth in the air sacs. Herein, we report the presence of disseminated infection with Aspergillus fumigatus in a 3-year-old male scarlet macaw parrot (Ara macao) that was presented to the Exotic Animal Clinic at the Faculty of Veterinary Medicine, Iași University of Life Sciences (Iași, Romania) for its postmortem examination. The confirmation of the fungal infection was achieved using histopathological, microbiological, and molecular methods. Since birds suffering from Aspergillus spp. do not always show respiratory issues, or their clinical signs are non-specific, this may create diagnostic difficulty for clinicians unfamiliar with the parrots' pathology. Therefore, for a definitive diagnosis, the demonstration of fungal presence by cytology or histopathology and its identification using culturing and molecular techniques is required. A 3-year-old male scarlet macaw parrot (Ara macao) was presented to the Exotic Animal Clinic at the Faculty of Veterinary Medicine, Iași University of Life Sciences (Iași, Romania) for its postmortem examination. According to the owner, the parrot had been raised only in captivity and after 5 days of inappetence, lethargy, and mild respiratory clinical signs, the parrot died. The post mortem examination revealed various-sized granulomas and caseous plaques in the lungs, air sacs, spleen, intestinal serosa, and liver. Microscopically, the granulomas were characterized by a necrotic center and the infiltration of numerous multinucleated giant cells and epithelioid-like cells and by the presence of hyphae typical of Aspergillus spp. Moreover, in the liver tissue, a diffuse inflammation, with numerous fungal hyphae, was noted. The fungal culture and the PCR assay allowed for the isolation and identification of Aspergillus fumigatus from the lung and liver samples. The macroscopical lesions and the histopathological findings, with the fungal isolation and molecular confirmation of Aspergillus fumigatus by nested PCR, provided the basis for the diagnosis of disseminated aspergillosis. To the authors' best knowledge, this is the first report of disseminated infection caused by Aspergillus fumigatus in a scarlet macaw parrot (Ara macao). [ABSTRACT FROM AUTHOR]

Aims: Low‐grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin‐specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft‐tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6‐rearranged tumours resembling NF with atypical features have been reported. Methods and Results: One index case of LGMS of the deltoid in a 56‐year‐old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break‐apart probe identified two additional cases. These cases were investigated with RNA‐sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low‐quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast‐like multinucleated giant cells, and peripheral lymphoid aggregates. Conclusion: Our findings support the notion that among soft‐tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas. [ABSTRACT FROM AUTHOR]

Ovarian aging results in reduced fertility, disrupted endocrine signaling, and an increased burden of chronic diseases. The factors contributing to the natural decline of ovarian follicles throughout reproductive life are not fully understood. Nevertheless, local inflammation may play an important role in driving ovarian aging. Inflammation progressively rises in aged ovaries during the reproductive window, potentially affecting fertility. In addition to inflammatory markers, recent studies show an accumulation of specific immune cell populations in aging ovaries, particularly lymphocytes. Other hallmarks of the aging ovary include the formation and accumulation of multinucleated giant cells, increased collagen deposition, and increased markers of cellular senescence. Collectively, these changes significantly impact the quantity and quality of ovarian follicles and oocytes. This review explores recent literature on the alterations associated with inflammation, fibrosis, cell senescence, and the accumulation of immune cells in the aging ovary. [ABSTRACT FROM AUTHOR]

The objective of our study was to evaluate early and late macroscopic and histological changes associated with the use of polycaprolactone dermal filler (PCL) in the orofacial region. Forty-eight female Wistar rats were divided into the PCL group and the control group. The material was applied to the ventral tongue and submandibular region, and the animals were euthanized at three time points—24 h, and 30 and 90 days. In the PCL group, yellowish nodules were observed on the tongue at all experimental time points. At the 24 h mark, the histological analysis revealed the presence of the PCL and a predominance of lymphocytes, plasma cells, and neutrophils. At 30 and 90 days, macrophages and multinucleated giant cells predominated around the PCL spheres. Collagen density in the dermis was higher in the PCL group when compared to the control at 30 and 90 days. In the submandibular glands, an inflammatory process similar to that observed at other sites was noted, with no alterations in acinar or ductal morphology. The results of this study highlight the effectiveness of PCL as a collagen biostimulator. Nevertheless, the development of nodular lesions on the tongue signals the potential risk of complications in mobile anatomical structures. [ABSTRACT FROM AUTHOR]

Polyploid giant cancer cells (PGCCs) are characterized by the presence of either a single enlarged nucleus or multiple nuclei and are closely associated with tumor progression and treatment resistance. These cells contribute significantly to cellular heterogeneity and can arise from various stressors, including radiation, chemotherapy, hypoxia, and environmental factors. The formation of PGCCs can occur through mechanisms such as endoreplication, cell fusion, cytokinesis failure, mitotic slippage, or cell cannibalism. Notably, PGCCs exhibit traits similar to cancer stem cells (CSCs) and generate highly invasive progeny through asymmetric division. The presence of PGCCs and their progeny is pivotal in conferring resistance to chemotherapy and radiation, as well as facilitating tumor recurrence and metastasis. This review provides a comprehensive analysis of the origins, potential formation mechanisms, stressors, unique characteristics, and regulatory pathways of PGCCs, alongside therapeutic strategies targeting these cells. The objective is to enhance the understanding of PGCC initiation and progression, offering novel insights into tumor biology. [ABSTRACT FROM AUTHOR]

This article presents two case studies of zebra finches that exhibited unusual symptoms. The first bird had infertility and swelling around the eyes, with abnormalities found in the oviduct and periocular skin. The second bird had oviductal prolapse, periocular dermatitis, and osteomyelitis. The cause of the symptoms in both cases was not definitively determined, but mycobacterium was found in the second bird. These findings emphasize the need for further research on the causes and impacts of these symptoms in zebra finches. [Extracted from the article]