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15 pages, 4366 KB  
Article
Authors’ Protocol of Central Giant Cell Granuloma Effective Treatment in the Jawbone
by Dominik Szczeciński, Patrycja Ujma, Katarzyna Radwańska, Piotr Szymor and Marcin Kozakiewicz
Cancers 2025, 17(21), 3510; https://doi.org/10.3390/cancers17213510 - 31 Oct 2025
Viewed by 235
Abstract
Background: Central giant cell granuloma of the jaw is a benign but potentially aggressive lesion that can cause pain, facial deformity, tooth loss, and jaw destruction. Many treatment methods are described in the literature, but the less invasive ones are associated with a [...] Read more.
Background: Central giant cell granuloma of the jaw is a benign but potentially aggressive lesion that can cause pain, facial deformity, tooth loss, and jaw destruction. Many treatment methods are described in the literature, but the less invasive ones are associated with a higher recurrence rate. For several decades, extensive bone resection procedures have been the most effective treatment to date. This study aimed to evaluate a minimally invasive treatment protocol combining multiple weekly intralesional steroid injections with surgical removal of residual tumor tissue and chemical cauterization using Carnoy’s solution. Methods: Thirteen patients with histologically confirmed central giant cell granulomas of the jaws were treated according to the protocol, including weekly triamcinolone injections and, when necessary, fenestration of the cortical bone to access residual lesions. Patients were monitored clinically and radiologically over six years, with reconstruction of bone defects using autogenous grafts and platelet-rich fibrin. Results: The treatment effectively reduced tumor size, restored cortical bone, and allowed preservation of jaw structure. Only one recurrence was observed, and complications were minor and transient. The protocol was equally effective for both aggressive and non-aggressive lesions, regardless of patient age or comorbidities. Conclusions: These findings suggest that combining pharmacological and surgical approaches with chemical cauterization provides a safe, effective, and tissue-preserving strategy for managing central giant cell granulomas, minimizing recurrence while reducing surgical morbidity. Full article
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17 pages, 631 KB  
Systematic Review
Salivary Gland Sarcoidosis: Systematic Review of Case Reports and Case Series
by Nadin Abouseif, Mohamed Jaber and Reem B. Abdelsayed
J. Clin. Med. 2025, 14(21), 7539; https://doi.org/10.3390/jcm14217539 - 24 Oct 2025
Viewed by 358
Abstract
Background: Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis that poses a challenge in terms of its diagnosis due to its similarities to disorders such as Sjögren’s syndrome, other granulomatous diseases, and infections. Objective: To systematically review reported cases [...] Read more.
Background: Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis that poses a challenge in terms of its diagnosis due to its similarities to disorders such as Sjögren’s syndrome, other granulomatous diseases, and infections. Objective: To systematically review reported cases of salivary gland sarcoidosis and summarize clinical presentation, diagnostic methods, treatments, and outcomes. Methods: We conducted a systematic search of PubMed, Scopus, Embase, ScienceDirect, and Medline for case reports and case series published up to April 2025. This review was registered with PROSPERO (CRD42024629263) and was conducted following PRISMA guidelines. Variables assessed included age, sex, presenting symptoms, location, duration of symptoms, treatment approaches, and outcomes. Study quality assessment was assessed using The Joanna Briggs Institute (JBI) Critical Appraisal tools. Results: A total of 28 articles involving 39 participants met the inclusion criteria, with a mean age of 42.7 years. Salivary gland sarcoidosis predominantly affected female patients (66.7%). The parotid gland was the most frequently involved site (82.1%). Common presenting features included glandular swelling that is usually painless, xerostomia, and facial palsy. Sarcoidosis was newly diagnosed in 82.1% of cases, primarily through histopathological examination revealing non-caseating granulomas. Systemic corticosteroids were the most common treatment. Outcomes were favorable in nearly all cases, with complete resolution post treatment or spontaneous remission without treatment. Conclusions: Salivary gland sarcoidosis predominantly affects middle-aged women, typically presenting as a painless parotid swelling and often serving as the initial sign of systemic disease. Diagnosis requires histopathological confirmation via biopsy, as serum ACE levels are insufficient alone. The prognosis is excellent, with most patients responding favorably to corticosteroids or even experiencing spontaneous resolution. This condition must be considered in differential diagnoses for persistent salivary gland swellings to ensure accurate diagnosis and prevent unnecessary interventions. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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15 pages, 1034 KB  
Article
Beyond Morphology: Quantitative MR Relaxometry in Pulmonary Lesion Classification
by Markus Graf, Alexander W. Marka, Andreas Wachter, Tristan Lemke, Nicolas Lenhart, Teresa Schredl, Jonathan Stelter, Kilian Weiss, Marcus Makowski, Dimitrios C. Karampinos, Daniela Pfeiffer, Gregor S. Zimmermann, Seyer Safi, Hans Hoffmann, Keno Bressem, Lisa Adams and Sebastian Ziegelmayer
Cancers 2025, 17(20), 3370; https://doi.org/10.3390/cancers17203370 - 18 Oct 2025
Viewed by 408
Abstract
Background/Objectives: Lung nodules present a common diagnostic challenge, particularly when benign and malignant lesions exhibit similar imaging characteristics. Standard evaluation relies on computed tomography (CT), positron emission tomography (PET), or biopsy, all of which have limitations. Quantitative magnetic resonance (MR) relaxometry using [...] Read more.
Background/Objectives: Lung nodules present a common diagnostic challenge, particularly when benign and malignant lesions exhibit similar imaging characteristics. Standard evaluation relies on computed tomography (CT), positron emission tomography (PET), or biopsy, all of which have limitations. Quantitative magnetic resonance (MR) relaxometry using native longitudinal relaxation time (T1) and transverse relaxation time (T2) mapping offers a radiation-free alternative reflecting tissue-specific differences. Methods: This prospective, single-center study included 64 patients with 76 histologically or radiologically confirmed lung lesions (25 primary lung cancers, 28 metastases, 9 granulomas, and 14 pneumonic infiltrates). The patients underwent T1 and T2 mapping at 3T. Two independent readers quantified the mean values for each lesion. The pre-specified primary endpoints were (1) benign versus malignant and (2) primary lung cancer versus pulmonary metastases. Results: Significant differences in T1 and T2 values were observed across lesion types. Benign lesions exhibited high T2 values (mean 213.6 ms) and low T1 values (mean 836.6 ms), whereas malignant tumors exhibited lower T2 values (~77–78 ms) and higher T1 values (~1460–1504 ms, p < 0.001). Binary classification yielded 95.7% accuracy (sensitivity 93.8% for malignant, specificity 100% for benign) in an internal 70/30 hold-out validation (no external dataset), with consistent performance confirmed by patient-level and nested cross-validation (balanced accuracy ≈ 0.92–0.94). However, malignant subtypes could not be reliably distinguished (p > 0.05), and multiclass accuracy was 60.9%. Conclusions: Quantitative MR relaxometry allows accurate, radiation-free differentiation of benign and malignant lung lesions and may help reduce unnecessary invasive procedures. Full article
(This article belongs to the Special Issue The Development and Application of Imaging Biomarkers in Cancer)
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12 pages, 262 KB  
Article
Evaluation of the Performance of StypCelTM Absorbable Hemostat for Intraoperative Hemorrhage Control in Neurosurgery: A Multicenter, Single-Arm Study in Riga, Latvia
by Kaspars Auslands, Evelina Kocane, Evija Bergfelde, Egils Valeinis, Julija Dolgopolova, Jekabs Aksiks and Igors Aksiks
Medicina 2025, 61(10), 1862; https://doi.org/10.3390/medicina61101862 - 16 Oct 2025
Viewed by 497
Abstract
Background and Objectives: Intraoperative bleeding during neurosurgical procedures poses a significant risk by increasing morbidity and mortality, obscuring the surgical field and prolonging operative time and hospitalization. Effective hemostasis is therefore essential, frequently necessitating the use of topical hemostatic agents. This study aimed [...] Read more.
Background and Objectives: Intraoperative bleeding during neurosurgical procedures poses a significant risk by increasing morbidity and mortality, obscuring the surgical field and prolonging operative time and hospitalization. Effective hemostasis is therefore essential, frequently necessitating the use of topical hemostatic agents. This study aimed to evaluate the performance of a plant-derived oxidized regenerated cellulose (ORC) hemostatic agent StypCel™ Absorbable Hemostat (Medprin Regenerative Medical Technologies Co., Ltd.) in various neurosurgical interventions, including intracranial tumor resections, spinal surgeries, trigeminal neuralgia operations, cerebrospinal fluid fistula repair and ventriculoperitoneal shunt implantation. The study aimed to assess its performance in these procedures due to the high risk of intraoperative bleeding and the challenges of achieving hemostasis in delicate neural structures. Materials and Methods: This prospective, single-arm clinical study included 46 patients who underwent neurosurgical procedures at three neurosurgerical clinics in Riga, Latvia. The primary endpoint was the rate of effective bleeding control achieved within 5 min of StypCel™ application. Safety assessments included monitoring for central nervous system infections (CNSI), intracranial granuloma formation, new-onset neurological deficits, seizures, anaphylactic reactions or device malfunction. All adverse events (AEs) and serious adverse events (SAEs) were documented during the postoperative follow-up. Results: The cohort consisted of 46 patients (29 females and 17 males), including 20 with neoplastic intracranial lesions and 26 with other neurosurgical pathologies. Effective bleeding control within 5 min was achieved in 93.5% of cases (95% CI: 82.1–98.6%). In three patients, bleeding control exceeded 5 min due to unexpected arterial hemorrhage encountered during intracranial tumor resection. No device-related AEs, SAEs, CNSIs or granuloma formations were reported throughout the follow-up period. Conclusions: The findings demonstrate that StypCel™ Absorbable Hemostat is a safe and effective adjunct for achieving intraoperative hemostasis in neurosurgical procedures. Its favorable safety profile and high hemostatic success rate support its clinical utility, particularly for controlling low-pressure venous or capillary bleeding. Further comparative and long-term studies are warranted to validate these results in broader surgical settings. Full article
(This article belongs to the Section Neurology)
26 pages, 4517 KB  
Review
Recent Advances in the Histopathology, Molecular Biology, and Treatment of Kaposi Sarcoma: A Contemporary Review
by Tayarv Jayd Bagratee, Veron Ramsuran, Mpumelelo Msimang and Pratistadevi Kanaye Ramdial
Int. J. Mol. Sci. 2025, 26(20), 10058; https://doi.org/10.3390/ijms262010058 - 16 Oct 2025
Viewed by 825
Abstract
Kaposi sarcoma (KS) is an intermediate-grade vascular tumour that has undergone major treatment and diagnostic breakthroughs following the discovery of Human herpesvirus 8 (HHV8). Whilst classically described in Eastern European populations, the endemic and epidemic forms of KS have facilitated its association with [...] Read more.
Kaposi sarcoma (KS) is an intermediate-grade vascular tumour that has undergone major treatment and diagnostic breakthroughs following the discovery of Human herpesvirus 8 (HHV8). Whilst classically described in Eastern European populations, the endemic and epidemic forms of KS have facilitated its association with AIDS. This was led by the detection of HHV8 by PCR, and thereafter, immunohistochemically. This not only enabled the recognition and diagnosis of complex histopathological KS subtypes but also facilitated distinction from its mimickers, including acroangiodermatitis and pyogenic granuloma. Recent advances in the viral genomics of HHV8 have expanded the diagnostic landscape of KS clinically and molecularly. The latent phase of replication in the HHV8 lifecycle reveals numerous angiogenic and inflammatory factors. Novel therapies targeting these viral–human molecular interactions may prove useful. However, this is highly dependent on the clonal nature of KS. Conflicting research outcomes demonstrate varying viewpoints on the clonal (monoclonal/oligoclonal/polyclonal) nature of KS, heightening the tumoural versus inflammatory pseudoneoplastic controversy. Understanding the clinical context of KS is fundamental to understanding its clonality, and a dearth of this clinical information in recent studies appears to be the critical factor in determining the true clonal nature of KS. The current molecular landscape, histopathology, treatment options, and opinions on clonality are critically reviewed. Full article
(This article belongs to the Special Issue Viral Infections and Cancer: Recent Advances and Future Perspectives)
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15 pages, 1053 KB  
Review
Vernix Caseosa Peritonitis: A Scoping Review
by Goran Augustin, Mislav Herman, Zrinka Hrgović, Ante Krešo and Jure Krstulović
Medicina 2025, 61(10), 1786; https://doi.org/10.3390/medicina61101786 - 3 Oct 2025
Viewed by 1205
Abstract
Background and Objectives: Vernix caseosa peritonitis (VCP) is rare. Nonspecific symptoms of acute abdomen during early puerperium make preoperative diagnosis of VCP challenging. We aimed to identify risk factors, early diagnosis and treatment options, and the association between the timing and severity [...] Read more.
Background and Objectives: Vernix caseosa peritonitis (VCP) is rare. Nonspecific symptoms of acute abdomen during early puerperium make preoperative diagnosis of VCP challenging. We aimed to identify risk factors, early diagnosis and treatment options, and the association between the timing and severity of VCP diagnosis and maternal outcomes. Materials and Methods: We searched PubMed, PubMed Central, and Google Scholar. Articles were analyzed according to the PRISMA guidelines. The search items included: ‘vernix caseosa peritonitis, ‘vernix caseosa granuloma, ‘maternal meconium peritonitis’, ‘maternal meconium granuloma’, ‘vernix caseosa’, ‘peritonitis’, ‘pregnancy’, ‘puerperium’, ‘postpartum’, and ‘gravid’. Additional studies were extracted by reviewing the reference lists of retrieved studies. Demographic, clinical, obstetric, diagnostic, and treatment parameters, and outcomes were collected. Results: Out of 55 published VCP case reports, 46 were available. Most involved term pregnancies (84.8%) and were delivered by Cesarean section (CS) (87%), with no difference in parity distribution (χ2(2) = 1.1875, p = 0.5523) or fetal sex (m: f = 53.3%: 46.7%). Common symptoms included abdominal pain and fever over 38 °C, while dyspnea or tachypnea was unexpectedly frequent (23.9%/15.2%). The interval from delivery to surgery ranged from 4 to 13 days (average 8 days), with no difference between CS and vaginal deliveries. Preoperative VCP was diagnosed in only 4.3% of cases, and intraoperative diagnosis occurred in 60.9%. Intraoperative microbiology and histopathology (vernix components) were positive in 6.5% and 89.1%, respectively. The birth weight was normal (3656 ± 509 g), with no maternal or neonatal deaths. Conclusions: VCP primarily develops in term pregnancies delivered by CS, without other risk factors. Despite extremely low preoperative and unexpectedly low intraoperative diagnosis and treatment delay of several days, there is no maternal or fetal mortality. The time to symptom onset is similar between women who delivered vaginally and those who had a CS. All women with VCP after vaginal delivery had previous deliveries. Abdominal pain with a fever over 38 °C and dyspnea or tachypnea in the early puerperium suggests VCP. Surgical lavage is the primary treatment, while corticosteroids have been reported to be beneficial in several cases, and antibiotics seem to have a limited role. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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10 pages, 372 KB  
Article
Benign and Malignant Tumors of the Hand: Patterns, Pathology, and Surgical Outcomes in a Large Retrospective Cohort
by Fabiana Battaglia, Roberta Giuffrida, Marco Pagano, Luigi Troisi and Gabriele Delia
Cancers 2025, 17(18), 3079; https://doi.org/10.3390/cancers17183079 - 21 Sep 2025
Viewed by 975
Abstract
Background: Hand tumors encompass a heterogeneous spectrum of benign, malignant, and tumor-like lesions with diverse clinical behavior. While international studies have reported epidemiological and clinicopathological features, large-scale data in Italian populations are scarce. This retrospective analysis represents one of the largest Italian surgical [...] Read more.
Background: Hand tumors encompass a heterogeneous spectrum of benign, malignant, and tumor-like lesions with diverse clinical behavior. While international studies have reported epidemiological and clinicopathological features, large-scale data in Italian populations are scarce. This retrospective analysis represents one of the largest Italian surgical series of histologically confirmed hand tumors. The objective was to evaluate clinicopathological characteristics, anatomical distribution, and surgical outcomes of these lesions over a 5-year period. Methods: A total of 250 patients who underwent surgery for hand tumors at the Department of Plastic and Reconstructive Surgery, University Hospital “G. Martino,” Messina, Italy, from January 2020 to December 2024, were retrospectively reviewed. Data from clinical records, imaging, and histopathology were categorized as tumor-like lesions, benign neoplasms, or malignant tumors. Demographic and clinical variables were compared across diagnostic groups. Results: The cohort included 127 males and 123 females (mean age 49.3 ± 18.6 years). Lesions were most frequently located in the digits (62%), followed by palm (21%), dorsum (11%), and wrist (6%). Tumor-like lesions represented 37.6% of cases, predominantly mucous cysts and foreign body granulomas. Benign tumors accounted for 49.2%, with giant cell tumors of the tendon sheath as the most common (31.7%). Malignant tumors were rare (10.4%), mainly squamous cell carcinoma, basal cell carcinoma, and melanoma. Patients with malignant lesions were significantly older (67.4 years) compared with those with benign or tumor-like lesions (p < 0.01). Conclusions: Benign and tumor-like lesions predominate among hand tumors, whereas malignancies are infrequent but clinically important. Surgical excision remains the treatment of choice, guided by preoperative imaging and confirmed histopathologically. Expanding this cohort and integrating molecular diagnostics with patient-reported outcomes may enhance future management strategies. Full article
(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)
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16 pages, 6289 KB  
Article
The Clinical Value of the Ferning Test in Monitoring Dry Eye Syndrome in Patients with Sarcoidosis
by Călina Anda Sandu, Cosmin Victor Ganea, Vlad Constantin Donica, Anisia Iuliana Alexa, Ioana Alexandra Sandu, Madalina Ioana Bilha and Camelia Margareta Bogdănici
Life 2025, 15(9), 1464; https://doi.org/10.3390/life15091464 - 18 Sep 2025
Viewed by 483
Abstract
Background: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, predominantly affecting the lungs and lymph nodes. However, the disease can affect any organ, including the eye, where it most commonly manifests as uveitis and dry eye disease (DED). [...] Read more.
Background: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, predominantly affecting the lungs and lymph nodes. However, the disease can affect any organ, including the eye, where it most commonly manifests as uveitis and dry eye disease (DED). The Ferning Test (FT), a non-invasive method for tear film analysis, offers insight into tear quality. Through this study, we aimed to evaluate the ability of the FT to diagnose and differentiate DED in patients with sarcoidosis. Methods: The study included a sample of 30 patients, divided into three groups, each consisting of 10 patients: one group of patients with sarcoidosis and dry eye disease (S-DED), one group of patients with DED without other systemic pathologies, and a control group of healthy individuals. Tear film samples were collected from the right eye of each participant, without stimulation, by microcapillarity. A drop of tear was spread on a microscope slide, allowed to dry, and then examined under a microscope to analyze the crystallization pattern. Results: Microscopic analysis revealed a significant difference in the structure and morphology of crystallization, as well as in the number of formed branchings, in sarcoidosis patients compared to patients in the other two groups. This finding suggests a distinct alteration in tear film composition in patients with sarcoidosis. Conclusions: Based on these results, the FT represents a valuable and promising tool for the diagnosis of DED associated with sarcoidosis. Being a non-invasive, easy-to-perform, and inexpensive test, it can be widely implemented in any ophthalmology department, opening perspectives for the test to become an important component among the diagnostic elements of dry eye syndrome in patients with sarcoidosis. Full article
(This article belongs to the Special Issue Prognosis and Management of Dry Eye Disease)
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20 pages, 1324 KB  
Review
Mycobacterium marinum Immune Evasion in Zebrafish
by Priyank Kumar, Joshua Cameron, Beatrice Saviola and Vishwanath Venketaraman
Pathogens 2025, 14(9), 908; https://doi.org/10.3390/pathogens14090908 - 10 Sep 2025
Cited by 1 | Viewed by 1160
Abstract
Fish mycobacteriosis, a chronic progressive disease caused by nontuberculous mycobacteria (NTM), affects marine, brackish, and freshwater fish. Mycobacterium marinum (M. marinum), the most important of the NTM, infects fresh and marine water fish causing necrotizing granulomas and associated morbidity and mortality. [...] Read more.
Fish mycobacteriosis, a chronic progressive disease caused by nontuberculous mycobacteria (NTM), affects marine, brackish, and freshwater fish. Mycobacterium marinum (M. marinum), the most important of the NTM, infects fresh and marine water fish causing necrotizing granulomas and associated morbidity and mortality. M. marinum causes disease in zebrafish in a dose-dependent fashion. The M. marinum-induced disease in the zebrafish is associated with the development of necrotizing granulomas with abundant bacteria in the necrotic areas. Acute infection with high infectious doses of M. marinum infection in zebrafish was characterized by uncontrolled replication of the pathogen and death of all fish within 16 days, while chronic infections were marked by the formation of granulomas in different organs and longer survival in the range of 4–8 weeks. This review therefore synthesizes recent advances in our understanding of M. marinum’s infection of zebrafish, molecular pathogenesis, virulence mechanisms, and immune evasion strategies in zebrafish, while also highlighting the host immune effector responses and the virulence mechanisms of M. marinum. Full article
(This article belongs to the Special Issue Infectious Diseases in Aquatic Animals)
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16 pages, 770 KB  
Review
Mast Cells in Tuberculosis: Immune Regulation, Allergic Environments, and Pathological Mechanisms
by Seung Hoon Lee, Gunhyuk Park, Hye-Sun Lim, Yoonseo Hong and Huiyun Seo
Allergies 2025, 5(3), 30; https://doi.org/10.3390/allergies5030030 - 4 Sep 2025
Viewed by 951
Abstract
Mast cells (MC) are key effector cells in allergic diseases and are increasingly recognized for their roles in the immunopathogenesis of tuberculosis (TB). In allergic conditions, MCs are hyperactivated, driving T-helper Type 2 (Th2)-skewed immune responses that may antagonize the T-helper Type 1 [...] Read more.
Mast cells (MC) are key effector cells in allergic diseases and are increasingly recognized for their roles in the immunopathogenesis of tuberculosis (TB). In allergic conditions, MCs are hyperactivated, driving T-helper Type 2 (Th2)-skewed immune responses that may antagonize the T-helper Type 1 (Th1)-mediated immunity essential for controlling Mycobacterium tuberculosis (Mtb) infection. This immunological imbalance may contribute to increased TB susceptibility, altered granuloma dynamics, and accelerated fibrotic remodeling. Histopathological and in vivo studies have revealed that MCs are recruited to TB lesions, where they release a spectrum of mediators, including histamine, IL-17A, TNF-α, TGF-β, tryptase, and chymase. These mediators can either support initial immune defense or promote chronic inflammation and tissue damage, depending on context and regulation. Moreover, individuals with chronic allergic diseases such as asthma and allergic rhinitis may experience worse TB outcomes due to their baseline immune dysregulation. Environmental exposures (e.g., air pollution, smoking), genetic polymorphisms (e.g., IL-4 −589C/T, IL-13 R130Q), and gut-lung axis disturbances further modulate MC activity and TB pathogenesis. This review synthesizes current findings on MC involvement in TB, particularly in allergic settings, and highlights the need for epidemiological studies and mechanistic research. It also explores the promise of host-directed therapies (HDTs) that target MCs or their mediators, such as antihistamines, MC stabilizers, leukotriene inhibitors, and cytokine modulators, as novel adjuncts to standard TB treatment. Personalized approaches that consider immune profiles, genetic risk, and comorbid allergies may improve TB outcomes and inform future clinical guidelines. Full article
(This article belongs to the Section Physiopathology)
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26 pages, 5439 KB  
Article
Methods for Evaluating the Effects of 2D and 3D Culture Environment on Macrophage Response to Mycobacterium Infection
by Danielle L. Stolley, Komal S. Rasaputra and Elebeoba E. May
Microorganisms 2025, 13(9), 2026; https://doi.org/10.3390/microorganisms13092026 - 29 Aug 2025
Viewed by 1027
Abstract
Macrophages are critical to the formation of infection- and non-infection-associated immune structures such as cancer spheroids, pathogen-, and non-pathogen-associated granulomas, contributing to the spatiotemporal and chemical immune response and eventual outcome of disease. While well established in cancer immunology, the prevalence of using [...] Read more.
Macrophages are critical to the formation of infection- and non-infection-associated immune structures such as cancer spheroids, pathogen-, and non-pathogen-associated granulomas, contributing to the spatiotemporal and chemical immune response and eventual outcome of disease. While well established in cancer immunology, the prevalence of using three-dimensional (3D) cultures to characterize later-stage structural immune response in pathogen-associated granulomas continues to increase, generating valuable insights for empirical and computational analysis. To enable integration of data from 3D in vitro studies with the vast bibliome of standard two-dimensional (2D) tissue culture data, methods that determine concordance between 2D and 3D immune response need to be established. Focusing on macrophage migration and oxidative species production, we develop experimental and computational methods to enable concurrent spatiotemporal and biochemical characterization of 2D versus 3D macrophage–mycobacterium interaction. We integrate standard biological sampling methods, time-lapse confocal imaging, and 4D quantitative image analysis to develop a 3D ex vivo model of Mycobacterium smegmatis infection using bone-marrow-derived macrophages (BMDMs) embedded in reconstituted basement membrane (RBM). Comparing features of 2D to 3D macrophage response that contribute to control and resolution of bacteria infection, we determined that macrophages in 3D environments increased production of reactive species, motility, and differed in cellular volume. Results demonstrate a viable and extensible approach for comparison of 2D and 3D datasets and concurrent biochemical plus spatiotemporal characterization of initial macrophage structural response during infection. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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9 pages, 4473 KB  
Case Report
Cholesterol Granuloma of the Frontal Sinus Complicated by Mycetoma: A Rare Case Report
by Chiara Rustichelli, Alessandro Serrone, Giovanni Cavallo, Antonino Maniaci and Gian Luca Fadda
Sinusitis 2025, 9(2), 15; https://doi.org/10.3390/sinusitis9020015 - 25 Aug 2025
Viewed by 720
Abstract
Cholesterol granuloma is an uncommon inflammatory lesion whose etiology is still unclear. It is thought to originate from blood accumulation in a pneumatized space, probably after bleeding. The most frequent site is the petrous apex of the temporal bone, whilst it is very [...] Read more.
Cholesterol granuloma is an uncommon inflammatory lesion whose etiology is still unclear. It is thought to originate from blood accumulation in a pneumatized space, probably after bleeding. The most frequent site is the petrous apex of the temporal bone, whilst it is very uncommon in the paranasal sinuses. We present a clinical case of an 80-year-old female patient with intense frontal headache and diplopia who underwent a neuro-navigated endoscopic sinus surgery. The histological diagnosis was a cholesterol granuloma of the frontal sinus, contaminated by Aspergillus Fumigatus hyphae. Cholesterol granuloma of the frontal sinus is a rare finding in clinical practice, but it should be taken into account in the diagnostic path in presence of rapidly increasing sight alterations and headache, even without rhinological symptoms. Full article
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16 pages, 1844 KB  
Article
Granulomatous Lesions in the Head and Neck Region: A Clinicopathological, Histochemical, and Molecular Diagnostic Study
by Amjad S. Ali and Bashar H. Abdullah
Diagnostics 2025, 15(16), 2055; https://doi.org/10.3390/diagnostics15162055 - 16 Aug 2025
Viewed by 1875
Abstract
Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed [...] Read more.
Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies—particularly Mycobacterium tuberculosis—in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh–Neelsen (ZN), Periodic acid–Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at p ≤ 0.05. Results: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (p = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (p = 0.004). Conclusions: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 1041 KB  
Article
Anti-Inflammatory Effects of Helianthus Tuberosus L. Polysaccharide and Its Limited Gene Expression Profile
by Evgenii Generalov, Leonid Yakovenko, Arkady Sinitsyn, Alexander Alekseev, Olga Sinitsyna, Khurshed Abduvosidov, Vladislav Minaichev and Liubov Generalova
Int. J. Mol. Sci. 2025, 26(16), 7885; https://doi.org/10.3390/ijms26167885 - 15 Aug 2025
Viewed by 731
Abstract
Previous studies have demonstrated that Helianthus tuberosus L. polysaccharide (HTLP) exhibits potent immunomodulating activity. The aim of this study was to investigate the molecular mechanisms underlying this activity and explore its potential applications in various anti-inflammatory models. We examined the anti-inflammatory potential of [...] Read more.
Previous studies have demonstrated that Helianthus tuberosus L. polysaccharide (HTLP) exhibits potent immunomodulating activity. The aim of this study was to investigate the molecular mechanisms underlying this activity and explore its potential applications in various anti-inflammatory models. We examined the anti-inflammatory potential of HTLP using in vitro and in vivo models. In vitro, we assessed the impact of HTLP on the expression of key inflammatory genes (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, CSF1, and NAMPT) in lipopolysaccharide (LPS)-stimulated THP-1 cells. In vivo, we employed rat pocket granuloma and formalin- and carrageenan-induced oedema models. HTLP significantly reduced oedema volume in the in vivo models. In the carrageenan-induced oedema model, HTLP exhibited efficacy significantly higher than that of ibuprofen, reducing oedema by 76% at 8 h (p < 0.01). In the air pouch granuloma model, HTLP showed comparable anti-inflammatory activity to ibuprofen. In the formalin-induced oedema model, HTLP reduced oedema, demonstrating less efficacy than ibuprofen, with a reduction of 58% versus ibuprofen’s 65% (p < 0.001). The anti-inflammatory mechanism of HTLP involves not only the suppression of pro-inflammatory cytokine expression (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, and CSF1) but also the activation of cell survival and cellular defence mechanisms (NAMPT) and the upregulation of the anti-inflammatory cytokine (IL10). The observed biological activity of HTLP suggests its potential as a valuable therapeutic agent for inflammatory conditions. The combination of functional and molecular evidence demonstrates HTLP’s potent anti-inflammatory properties across multiple models, with efficacy approaching or exceeding that of ibuprofen in certain models. However, further studies are necessary to fully elucidate its mechanism of action and to evaluate its long-term efficacy and safety. Full article
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Interesting Images
The Occurrence of Mandible Brown Tumor Mimicking Central Giant Cell Granuloma in a Case Suspicious of Primary Hyperparathyroidism—Troublesome Diagnostic Dilemmas
by Kamil Nelke, Klaudiusz Łuczak, Maciej Janeczek, Marcelina Plichta, Agata Małyszek, Małgorzata Tarnowska, Piotr Kuropka and Maciej Dobrzyński
Diagnostics 2025, 15(16), 2038; https://doi.org/10.3390/diagnostics15162038 - 14 Aug 2025
Cited by 1 | Viewed by 737
Abstract
The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological [...] Read more.
The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological appearance lesions, they can sometimes extend between the displaced tooth roots or cause their resorption. The scope of cortical bone in radiographic studies might have a different status, and lesions can spread outside of the bone. If no odontogenic feature is present, an additional blood examination for bone markers and calcium–phosphate markers is useful to establish any endocrine-related pathologies. In the primary hyperparathyroidism (PHP), bone blood markers and bone scintigraphy are very useful to establish the possible occurrence of brown tumor. On the other hand, in central giant cell granuloma (CGCG), only a direct tumor lesion biopsy might confirm the diagnosis, where in microscopic evaluation, mostly fibroblasts and secondary cells have multinucleated giant cells along with some accessory cells like macrophages, dendrocytes, and other endothelial cells. Because both lesions can have similar clinical and radiological appearances and unclear borders, with different shapes, sizes, and symptoms, it is quite important to compare both clinical and radiological patient characteristics. The authors aim to present how radiological studies alone can easily lead to lesion misdiagnosis. They also aim to emphasize how local treatment methods without advanced microsurgical reconstruction can, in some cases, improve patient outcomes. Full article
(This article belongs to the Collection Interesting Images)
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