Search Results (3,089)

Background: Orthodontically driven osteogenesis (ODO) is a surgical tunnel modification of periodontally accelerated osteogenic orthodontics (PAOO), combining selective corticotomy with bone grafting in sequential and/or segmental fashion. This is a minimally invasive approach that enhances periodontal health and allows orthodontic tooth movement beyond the original alveolar envelope. Considering the lack of long-term three-dimensional data on orthodontically driven osteogenesis (ODO), this study aims to quantitatively assess the long-term stability of alveolar bone and buccal cortical thickness following ODO, using CBCT imaging. The null hypothesis is that ODO does not result in significant changes in alveolar bone volume or cortical thickness over a seven-year follow-up period. Methods: Twenty patients (13 females, 7 males; mean age 27.4 ± 5.3 years) who had undergone orthodontically driven osteogenesis (ODO) using a minimally invasive tunnel approach and segmental corticotomy protocol followed by clear aligner therapy were retrospectively evaluated. The mean follow-up period after treatment was 7 years (range: 5–15 years). Cone beam computed tomography (CBCT) scans were obtained at one year postoperatively (T1) and again at the long-term follow-up visit (T2). Buccal bone thickness measurements were taken at standardized levels (3 mm, 5 mm, and 7 mm apical to the cementoenamel junction) and compared between T1 and T2 to evaluate bone stability over time. In addition, histologic evaluation of the previously grafted area was performed in two patients: one sample was collected during an alveolar ridge augmentation procedure six months after ODO, and the other during orthognathic surgery eight months after ODO. The samples were analyzed to assess new bone formation and integration of graft material. Results: Radiographic analysis showed long term stability of the new bone support. Histologic examination showed newly formed lamellar and reticular bone. Bone marrow showed no inflammatory infiltration, and bone particles were still detectable but incorporated in the newly created bone. Conclusions: Based on these findings, ODO appears to be a promising technique that could induce stable bone osteogenesis. A larger cohort study can enhance the evidence of these promising results to popularize this technique. Full article

In the spring of 2023, a disease outbreak occurred in Lake Taihu in China, which caused a large number of deaths of H. nobilis. In order to investigate the cause of morbidity and mortality of the H. nobilis, the diseased fish were collected for histopathological and etiological studies. Histopathological observation revealed that substantial inflammatory cell infiltration was observed around skin lesion in diseased fish, extensive degeneration and necrosis were observed in the hepatic parenchymal cells, the spleen exhibited congestion, and the kidney showed hemorrhage. A bacterial strain, C1, isolated from diseased H. nobilis was identified as Iodobacter fluviatilis through 16S rRNA gene sequencing and biochemical phenotypic characterization. Experimental infection of the fish via intramuscular injection induced a subcutaneous abscess-like lesion in a subset of fish. Antimicrobial susceptibility testing revealed that the isolate was susceptible to aminoglycosides, tetracyclines, quinolones and amphenicols, but resistant to sulfonamides commonly used in aquaculture. Here, we describe an association between I. fluviatilis and skin lesions in H. nobilis. Furthermore, we report the biochemical characteristics and drug resistance profile of the isolated bacteria. These findings also facilitate further investigations into the role of I. fluviatilis associated with skin diseases of H. nobilis and other freshwater fish. Full article

Background/Objectives: Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory cardiomyopathy driven by eosinophil cytotoxicity and extracellular trap formation. Interleukin-5 (IL-5) inhibition may disrupt this pathogenic cascade. We reviewed contemporary evidence on IL-5 blockade in EM and contextualized it with an illustrative case. Methods: We searched PubMed through May 2025 for reports of EM treated with mepolizumab or benralizumab. Inclusion criteria were consistent with prior cohorts: acute cardiac symptoms with biomarker elevation plus abnormalities on transthoracic echocardiography and/or cardiac magnetic resonance imaging (CMR), along with documented IL-5-targeted therapy. We extracted clinical, imaging, biopsy, treatment-timing, and outcome data and included one institutional case. Results: Twenty-one episodes were analyzed (median age, 45 years; 10 men). Underlying conditions included eosinophilic granulomatosis with polyangiitis (10 cases; 48%), hypereosinophilic syndrome (5 cases; 24%), drug reaction with eosinophilia and systemic symptoms (DRESS, 3 cases; 14%), and eosinophilic asthma (3 cases; 14%). Treatments involved mepolizumab in 17 cases (81%) and benralizumab in 4 (19%); 4 patients received “early-start” therapy within 14 days of EM diagnosis. Among the 11 episodes with reported left ventricular ejection fraction (LVEF) at baseline and follow-up, the median baseline LVEF was 40% (range, 30–62), with 10 of 11 (91%) <50%. On follow-up, all 11 patients improved: 4 normalized (≥50%) and 7 improved to 40–49%. CMR (n = 18) demonstrated late gadolinium enhancement in 14 cases (78%), edema in 9 (50%), and intracardiac thrombus in 4 (22%). Endomyocardial biopsy confirmed eosinophilic infiltration in 13 of 15 cases (87%). Outcomes included one death (fulminant DRESS), one recovery following veno-arterial extracorporeal membrane oxygenation, and one successful heart transplantation. Illustrative case: A 24-year-old man on a steroid taper received mepolizumab 300 mg on Day 4. His LVEF improved from 47% to 59% by Day 15, accompanied by biomarker decline and successful steroid tapering. Conclusions: Across published cases and our institutional experience, IL-5–targeted therapy appears safe, steroid-sparing, and associated with rapid ventricular recovery, particularly when initiated early. Although limited, these findings support the need for prospective trials to define the optimal agent, dosing, timing, and integration with standard immunosuppression and anticoagulation. Full article

Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10–30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory failure, and death. Oral glucocorticoids remain the cornerstone of treatment for symptomatic patients with pulmonary infiltrates and abnormal pulmonary function tests, with typical starting doses ranging from 20 to 40 mg/day followed by a slow taper over 6–18 months based on clinical and radiographic response. However, prolonged glucocorticoid therapy is associated with significant toxicity, and many patients require additional immunosuppressive agents for disease control or steroid-sparing purposes. Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies—including RCI, rituximab, JAKi or investigational regimens—are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm. Full article

This study aimed to evaluate the effects of different dosimetric parameters of photobiomodulation therapy (PBMT) in an experimental model of chronic obstructive pulmonary disease (COPD). C57BL/6 mice were assigned to the following groups: Baseline, COPD, and COPD treated with PBMT at doses of 1 J, 3 J, 5 J, and 7.5 J. Treatment was performed using a diode laser (660 nm, 100 mW) applied for 10 s, 30 s, 50 s, and 120 s, respectively, over 15 consecutive days. COPD was induced by orotracheal instillation of cigarette smoke extract twice weekly for 45 days. Analyses included total cell count, immune cell profiling by flow cytometry, pulmonary infiltration of inflammatory markers, necrosis, apoptosis, and reactive oxygen species (ROS) production. Data were analyzed using one-way ANOVA followed by the Newman–Keuls post hoc test, with statistical significance set at p < 0.05. PBMT significantly reduced inflammatory cell infiltration, with the most pronounced anti-inflammatory effects observed at doses of 1 J and 3 J, highlighting the importance of appropriate dosimetry in optimizing the therapeutic outcomes of PBMT for COPD. Full article

Cutaneous metastases (CMs) represent an uncommon but clinically significant manifestation of advanced malignancies, originating from both solid and non-solid cancers. This review explores the clinical characteristics and prognostic implications of CMs. For solid cancers, CMs are most frequently associated with primary malignancies of the breast, lung, and gastrointestinal tract, presenting as nodules, plaques, or ulcerative lesions. In contrast, CMs from non-solid cancers, such as hematologic malignancies, often exhibit distinct patterns, including diffuse infiltrates or erythematous plaques, mimicking inflammatory dermatoses. Clinical features, as well as dermoscopy, may help, but diagnostic confirmation relies on histopathological evaluation and immunohistochemical studies, which are essential for determining the primary source of the malignancy. Clinically, CMs often signify a poor prognosis, necessitating prompt recognition and tailored management to improve patient outcomes. This comprehensive review aims to enhance clinical understanding and awareness of CMs to facilitate early diagnosis and optimized treatment strategies. Full article

Background: Dibutyl phthalate (DBP) is a prevalent environmental pollutant that can accumulate in organisms, becoming amplified after the food cycle and ultimately affecting human health. Recent studies have provided evidence suggesting a potential association between exposure to DBP and cardiovascular diseases (CVDs). Objectives: This study’s objective is to investigate the toxic cardiovascular effects of long-term exposure to DBP, particularly its impact on the heart and blood vessels. To be specific, we hypothesized and verified the potential mechanisms underlying DBP-induced cardiac and vascular injuries, focusing on oxidative stress, pyroptosis, inflammatory responses, and metabolic pathways. Methods: The rats were divided into 5 groups: Control group, DBP-Low group, DBP-Medium group, DBP-High group, and DBP-High + Vitamin E group. The entire experimental period lasted 12 weeks. We conducted examinations on echocardiography, histopathology, oxidative stress biomarkers, pyroptosis-related biomarkers, and inflammatory cytokine biomarkers. Additionally, we carried out serum metabolomics analysis. Result: Our research findings indicate that long-term exposure to DBP can cause significant toxic effects on the cardiovascular system. Specifically, DBP leads to changes in oxidative stress indicators (ROS and an increase in MDA levels, alongside a decrease in GSH levels) and protein levels related to pyroptosis (NLRP3, Caspase-1 and GSDMD levels increase) in cardiac and vascular tissues, triggering oxidative inflammatory responses (IL-1β and IL-18 levels increase), damaging the heart and blood vessels (organizational structure deformation and collagen fiber infiltration) and ultimately affecting their functions (abnormalities in cardiac function and hemodynamics). Additionally, the results of metabolomics studies suggest that metabolic pathways (Biotin metabolism, TCA cycle, Vitamin B6 metabolism, Pantothenate and CoA biosynthesis, and Riboflavin metabolism) and metabolites may also be of great significance. Conclusion: Long-term exposure to DBP can induce cardiovascular toxicity in rats, manifesting as cardiac and vascular damage, as well as alterations in organ function. This process is characterized by oxidative stress, activation of the pyroptosis pathway, inflammatory responses, and modifications to metabolic pathways. Full article

Immunoglobulin G4–related disease (IgG4-RD) is an uncommon fibro-inflammatory process characterized by the infiltration of tissues and organs and a typically dramatic response to glucocorticoids. Its relapsing–remitting course, multisystemic involvement, and variability in epidemiological and prognostic features pose a significant diagnostic challenge for clinicians. Despite their effectiveness in symptom relief, prolonged glucocorticoid use remains a challenge in IgG4-RD management, prompting the search for steroid-sparing alternatives. Although rituximab has recently demonstrated efficacy in the treatment of IgG4-RD, no consensus exists regarding the optimal maintenance regimen. The emergence of new B-cell–targeted therapies and other immunomodulators represents a promising step toward more personalized treatment approaches. In this review, we provide an updated and integrative overview of the emerging treatment strategies for IgG4-RD, highlighting future directions towards individualized management. Full article

Background/Objective: Oral lichen planus (OLP) is a chronic inflammatory, immune-mediated mucosal condition classified as a potentially malignant disorder due to its risk of progression to oral squamous cell carcinoma (OSCC). The molecular events linking chronic inflammation in OLP to epithelial dysplasia remain poorly defined. To evaluate the expression of six immunohistochemical markers: IL-17, Maspin, β-Catenin, TIMP-1, MMP-14 and Syndecan-4 in OLP specimens and to explore their association with clinicopathological features and early dysplastic changes. Methods: We conducted a retrospective, cross-sectional study including 63 cases of OLP and 20 healthy controls. Formalin-fixed, paraffin-embedded sections underwent immunohistochemical staining for the six markers. Semi-quantitative scoring of staining intensity and percentage of positive cells was performed independently by two blinded pathologists. Results: IL-17 was markedly upregulated in 82.5% of OLP lesions versus absence in controls, correlating strongly with inflammatory infiltrate intensity. β-Catenin exhibited cytoplasmic and nuclear accumulation in 88.9% of OLP samples, with nuclear localization significantly associated with moderate dysplasia. Syndecan-4 membrane expression was reduced in dysplastic lesions, while Maspin and TIMP-1 co-expression were more prevalent in non-dysplastic OLP. MMP-14 was weakly positive in 87.3% of OLP cases and correlated with neovascularization. Conclusions: Elevated IL-17 expression and nuclear localization of β-Catenin may contribute to the progression of OLP toward dysplastic transformation, with this pattern being most evident in the erosive subtype. These findings suggest that a combined immunohistochemical panel may support risk stratification in OLP, although validation in larger, prospective cohorts is warranted. Full article

Dermoscopy is an essential, non-invasive diagnostic tool that has transformed the evaluation of pigmented skin lesions and is nowadays also increasingly recognized for its utility in general dermatology. Originally developed for the early detection of melanoma, dermoscopy now aids in diagnosing a wide range of non-neoplastic skin disorders—including inflammatory, infectious, and infiltrative conditions—by revealing morphological features invisible to the naked eye. Among these, facial dermatoses represent a diagnostically challenging group of disorders with overlapping clinical presentations. This review provides a comprehensive overview of the latest literature on dermoscopy in general dermatology, with a specific focus on facial dermatoses. Relevant information for this article was obtained through a comprehensive PubMed search using disease names along with the terms ‘dermoscopy’ and ‘dermatoscopy’. Despite its growing relevance, this field remains underexplored, largely due to the lack of standardized dermoscopic criteria and inconsistent terminology, which pose challenges to broader clinical implementation. Nonetheless, current evidence highlights the promising role played by dermoscopy as an adjunctive diagnostic method, particularly when used by experienced clinicians in combination with detailed patient history and clinical examination. Dermoscopy of facial dermatoses has the potential to significantly improve diagnostic precision in everyday practice. With continued research, greater standardization, and wider clinician training, dermoscopy is well-positioned to become as integral to the diagnosis of inflammatory and infectious dermatoses as it is to skin cancer detection. Full article

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

Brazilian red propolis (BRP) has emerged as a promising source of multifunctional phytochemicals with potent anti-inflammatory activity. This review provides a comprehensive analysis of the anti-inflammatory effects of BRP’s bioactive compounds, their molecular targets, and their mechanisms of action. Isolated compounds from BRP (such as formononetin, biochanin A, daidzein, calycosin, medicarpin, vestitol, and neovestitol) have demonstrated the ability to modulate critical pro-inflammatory signaling pathways, including NF-κB, TLR4, JAK/STAT, and PI3K/AKT, while concurrently activating antioxidant and cytoprotective responses via the Nrf2/HO-1 axis. These effects are further supported by the suppression of pro-inflammatory cytokines, regulation of immune cell infiltration and activation, inhibition of inflammasome components such as NLRP3, induction of autophagy, and polarization of macrophages and microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype. Collectively, these findings reinforce the potential of BRP as a rich source of multifunctional phytochemicals with broad therapeutic relevance for chronic inflammation and related pathologies. Future research should address the identified knowledge gaps by employing rigorous in vitro and in vivo toxicity assessments, exploring structure–activity relationships, and leveraging advanced delivery systems to optimize bioavailability. Such methodological approaches will be essential for translating the promising biological activities of BRP compounds into clinically viable therapeutic agents. Full article

Background/Objectives: Microglia are the primary immune cells in the central nervous system (CNS) and are known as “resident” macrophages. The aim of this study was to determine the effect of acute ethanol (EtOH) on the microglia state and monocyte infiltration into the CNS, with particular attention to the role of peripheral and central dopamine (DA) D2 receptors (D2Rs) in mediating EtOH effects on peripheral and central substrates. We hypothesize that EtOH interacts with peripheral immune mediators via D2Rs including monocyte-derived macrophages (MDMs) to modulate midbrain neurons, DA transmission in the mesolimbic pathway from the ventral tegmental area (VTA) to nucleus accumbens (NAc), and the intoxicating effects of acute EtOH. Methods: Using the Macrophage FAS-Induced Apoptosis (MaFIA) mouse model (GFP+ on Csf1r promoter), we assessed the effects of three intraperitoneal (IP) doses of EtOH (1, 2, and 4 g/kg) at three time points (0.5, 1, and 2 h after injection) on D2R expression in blood leukocytes and microglia, as well as midbrain neuronal activity, DA release, and behavior. Results: Acute EtOH significantly enhanced lymphocyte and monocyte D2R expression at 1.0 g/kg by 2 h after injection in vivo but decreased D2R expression in vitro. Ethanol enhanced microglia D2R expression in the NAc, while not altering D2R expression in the VTA, but altered the microglia state in these areas, shifting them toward an inflammatory phenotype. Acute EtOH induced prolonged and progressive hypersensitivity of D2R activation of VTA GABA neurons. Intravenous injection of the macrophage depleter liposomal clodronate significantly reduced blood macrophages by 55.3% and blocked the typical inhibition of VTA GABA neurons by EtOH, as well as the enhancement of DA levels in the NAc, and the locomotor indices of intoxication produced by acute EtOH, but not choice place preference. Conclusions: These findings strongly suggest a neuroimmune peripheral connection for acute low-dose EtOH use and challenge the dogma that central actions of EtOH exclusively mediate its effect on DA neuronal activity and release. Full article

Background/Objectives: The dysregulation of NLRP3 inflammasome activation has been established as a key driver of inflammatory disease pathology, which marks NLRP3 as an attractive therapeutic target. However, the clinical development of NLRP3 inhibitors such as MCC950 has been hampered by their associated toxicity profiles, highlighting an unmet clinical need. Methods: Herein, we present LMT2368, a novel urea-based NLRP3 inhibitor identified through screening of urea-based derivatives from our in-house compound library. Results: Biolayer interferometry confirmed direct binding of LMT2368 to the NLRP3 NACHT domain with a (K_D = 27.4 ± 1.2 μM which was superior to MCC950. Molecular docking studies predicted enhanced binding interactions for LMT2368, consistent with its improved biological activity. In LPS-primed macrophages, LMT2368 dose-dependently suppressed IL-1β secretion (IC50 = 0.8 μM in J774A.1 cells) and caspase-1 activation without affecting NF-κB signaling. Importantly, LMT2368 inhibited ASC oligomerization and pyroptosis while maintaining excellent safety margins (CC50 > 50 μM). In a murine model of LPS-induced acute lung injury, LMT2368 (10 mg/kg) reduced bronchoalveolar lavage fluid immune cell infiltration by 68% (p < 0.001), suppressed pro-inflammatory cytokine release (IL-1β/IL-6/TNF-α), and preserved lung histoarchitecture. Notably, LMT2368 showed selectivity for NLRP3 inhibition without affecting TNF-α/IL-6 production during TLR4 priming in monocytic cell lines. Conclusions: Together, these findings establish LMT2368 as a promising lead compound for developing safer NLRP3 inhibitors with therapeutic potential for inflammasome-driven diseases. Full article

Polystyrene microplastic (PS-MP) particles disrupt aquatic biological systems due to their persistence and high bioaccumulation potential, causing structural damage and inflammatory responses. PS-MPs also act as metabolic disruptors, affecting glucose metabolism and insulin signaling, although the mechanisms underlying these effects remain unclear. In this study, grass carp were exposed to 100 μg/L and 400 μg/L of polystyrene MPs for 30 days. Histopathological analysis showed the shortening of intestinal villi, vacuolization, and inflammatory infiltration. Antioxidant enzyme activities (SOD and CAT) were reduced, while the presence of tissue damage markers (GPT and GOT) was elevated, suggesting a biphasic oxidative stress response. Transcriptomic analysis revealed downregulation of genes related to metabolism and insulin signaling, especially at 400 μg/L. Gene set enrichment analysis (GSEA) highlighted pathways related to insulin resistance and type 2 diabetes, indicating the disruption of glucose metabolism. Microbiome analysis showed reduced diversity, expansion of Proteobacteria (opportunistic pathogens), and a decrease in beneficial bacteria like Bacillus. These shifts correlated with changes in the expression of key insulin signaling genes, emphasizing the role of host–microbiota interactions in metabolic imbalances. This study revealed that PS-MPs disrupt glucose metabolism and insulin signaling in grass carp through a combination of histological damage, oxidative stress, and microbiota dysbiosis. Full article