Acute pancreatitis is an inflammatory condition characterized by an intense systemic inflammatory response and increased oxidative stress, which may compromise distant organs such as the lungs. In this context, natural compounds with antioxidant and anti-inflammatory properties have been investigated as potential therapeutic agents. Therefore, this study aimed to evaluate the effect of the fixed oil from Syagrus coronata in an experimental model of L-arginine-induced acute pancreatitis. Pancreatitis was induced in mice by two intraperitoneal injections of L-arginine (8%, 4 g/kg). Animals were orally treated with Syagrus coronata fixed oil (ScFO) at doses of 25, 50, or 100 mg/kg after disease induction. Serum biochemical parameters (amylase, lipase, and glucose), inflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress markers in lung tissue (MDA, SOD, and CAT), and histological alterations were evaluated. Pancreatitis induction significantly increased amylase, lipase, glucose, inflammatory cytokines, and lipid peroxidation, while reducing antioxidant enzyme activity in lung tissue. Treatment with ScFO at 50 mg/kg reduced amylase (35.12%), lipase (40.74%), and glucose levels (20.24%), whereas the 100 mg/kg dose produced reductions of 56.44%, 59.26%, and 30.95%, respectively. Decreases in IL-1β (32.05% and 52.56%), IL-6 (31.34% and 52.99%), and TNF-α (29.55% and 50%) were also observed at doses of 50 and 100 mg/kg. In lung tissue, the oil reduced MDA levels by 34.78% and 54.71% and increased SOD and CAT activity at higher doses. The 25 mg/kg dose showed no significant effect. These findings indicate that ScFO exerts a protective effect in experimental pancreatitis by reducing systemic inflammation and oxidative stress, particularly at doses of 50 and 100 mg/kg.
Prenatal alcohol exposure (PAE) is a major early-life stressor associated with long-lasting neurodevelopmental and neurocognitive alterations. Increasing evidence from human studies indicates that PAE leaves persistent molecular signatures that can be detected in the placenta and in clinically accessible biological fluids. This Mini Review summarizes recent advances in the identification of epigenetic, immune, endocrine, and RNA-based biomarkers measured in placental tissue, umbilical cord blood, and peripheral fluids, and their associations with neurodevelopmental outcomes. We highlight convergent findings across heterogeneous study designs, discuss current methodological challenges and research gaps, and consider future directions toward integrative and longitudinal biomarker approaches. Together, the reviewed evidence supports the potential of placental and circulating biomarkers to improve early risk stratification and to advance understanding of neurodevelopmental alterations following PAE.
Granulomatous enteritis in pigs is mostly associated with porcine circovirus 2 systemic disease (PCV2-SD) but less often caused by fungi, Salmonella spp., foreign bodies, Mycobacterium spp. or Lawsonia intracellularis. This unusual and rare presentation of Lawsonia intracellularis infection can only be diagnosed by histopathological and immunohistochemical confirmation. Postmortem examination was performed in three 9-10-week-old post-weaned growing pigs from an outdoor farm submitted with a clinical history of increased mortality and wasting over the last two batches. Gross findings in all animals included poor body condition, segmental fibrino-necrotizing enteritis and catarrhal colitis. Histopathological examination identified chronic segmental proliferative enteritis with concurrent granulomatous inflammation of the submucosa and Peyer's patches in one animal (pig A). Lawsonia intracellularis was demonstrated in the apical cytoplasm of proliferating crypt enterocytes and in multinucleated giant cells and macrophages of the lamina propria and submucosa by Warthin-Starry stain and immunohistochemistry. PCV2 antigen was not detected in the intestinal lesions or in other lymphoid tissues by immunohistochemistry. Mycobacteriosis was ruled out by means of Ziehl Neelsen stain. Selective culture of intestinal contents for Salmonella spp. was negative and Brachyspira pilosicoli was isolated and identified by PCR from two animals (pigs A and C). This spirochete could have contributed to the colitis and wasting in these animals. Porcine reproductive and respiratory syndrome virus involvement was discarded in the three pigs by spleen RT-PCR. This case report highlights Lawsonia intracellularis as a rare but significant differential diagnosis for granulomatous enteritis in pigs and emphasizes the importance of achieving a definitive diagnosis by excluding PCV2-SD and demonstrating co-localization of the bacterium with granulomatous inflammation by Warthin-Starry stain and immunohistochemistry.
Management of pain in the canine cervical spine is a challenge where regional anesthesia of the cervical dorsal branches via an interfascial plane approach can improve multimodal analgesia. This study aimed to describe the ultrasound-guided multifidus cervicis plane (US-MCP) approach in dogs and evaluate its distribution and nerve staining. An anatomical and sonoanatomical study was followed by an experimental phase using 15 ultrasound-guided injections performed at the C3 level (0.3 mL kg-1 of a methylene blue, iodinated contrast, and saline mixture) in canine cadavers. Contrast spread and nerve staining were evaluated using computed tomography (CT) and subsequent anatomical dissection. Sonoanatomical landmarks were consistently identified in all cases. CT contrast spread reached the C1-C2 levels cranially and C4-C5 caudally in most cases. Contrast distribution reached the dorsal midline in 12/15 injections. Epidural migration occurred in 4/15 cases, mainly at the C2-C3 level. Dissection confirmed accurate interfascial deposition in all specimens. Nerve staining was 100% effective (15/15) for the dorsal branches of C2 and C3 and 60% in the case of C4 (9/15). However, success rates decreased caudally and staining was observed in 13.3% (2/15) of C5 nerves, and was absent (0/15) at C6. The described US-guided MCP approach is a feasible and highly specific technique for the desensitization of the cranial dorsal cervical region. Consistent staining of the C2 and C3 dorsal branches, and potentially C4, supports its potential as a promising tool for integration into multimodal analgesia protocols. Clinical studies are required to evaluate its safety and analgesic efficacy.
Upper digestive tract neoplasms associated with ingestion of Pteridium spp. (bracken fern) have been documented in cattle but not in buffalo. Here, we describe upper digestive tract lesions associated with the ingestion of P. esculentum subsp. arachnoideum in 3 water buffalo (Bubalus bubalis) in Brazil. Gross inspection revealed proliferative and ulcerative lesions in the mucosa of the base of the tongue, oropharynx, and esophagus in all 3 cases. Proliferative lesions were well-demarcated, white-to-brown, exophytic nodules on the lingual and oropharyngeal mucosa (papillomas, cases 1-3); a well-demarcated, white nodular fibroma in the distal esophageal submucosa (case 1); and locally infiltrative areas of mucosal thickening with ulceration and dark red-to-brown areas of hemorrhage in the base of the tongue and oropharynx (squamous cell carcinomas [SCCs], cases 1-3). Histologically, non-neoplastic lesions were irregular (cases 2, 3) or pseudocarcinomatous (case 1) mucosal hyperplasia with parakeratosis (cases 1-3) and dysplasia (cases 1, 2) in the base of the tongue, oropharynx, and esophagus. Neoplastic lesions were papillomas affecting the base of the tongue, oropharynx, and esophagus (cases 1-3); a submucosal distal esophageal fibroma (case 1); and SCCs affecting the base of the tongue and oropharynx (cases 1-3). Mucosal ulceration was associated with the SCCs in all cases. Inflammation was lymphoplasmacytic. Esophageal vascular myxomatous degeneration or proliferation with fibrosis were present. The diagnoses of Pteridium-associated disease were based on the epidemiologic and pathologic findings, which were identical to those observed in cattle.
Glioblastoma (GBM) is the most aggressive tumor in the Central Nervous System for which the standard-of-care treatment is still limited to maximal surgical resection followed by chemotherapy and radiotherapy. Thus, innovative strategies have been investigated to improve GBM treatment and increase patient overall survival. In this work we investigated a putative role for Thiamet G (TMG), an O‑GlcNAcase (OGA) inhibitor, in modulating the angiogenic capacity of GBM secretome using label-free mass spectrometry followed by in vitro validations. In silico analysis showed that TMG treatment of U87-MG GBM cells led to an enrichment of Extracellular Matrix (ECM)-related pathways associated with angiogenic biological processes, or the AngioMatrix, in the GBM secretome coupled to significant fold change of Thrombospondin-2 (THBS2), C-C motif chemokine 2 (CCL2) and Interleukin-6 (IL-6). Among them, only THBS2 gene alteration and CCL2 gene expression were significantly related to overall survival in GBM patients. Further in vitro validation exposing endothelial cells to TMG-treated GBM secretome showed aberrant tubulogenesis and migration, indicating that TMG treatment of GBM cells functionally disrupted the tumor cell capacity of modulating angiogenesis-related processes in vitro. These pioneering results demonstrate the impact of TMG on the AngioMatrix signature of the GBM secretome bridging pharmacological inhibition of OGA activity with innovative approaches targeting anti-angiogenic therapy for GBM treatment.
Psoriatic arthritis (PsA) is a chronic inflammatory disease with a complex clinical spectrum. Sphingosine-1-phosphate (S1P) and its receptor (S1PR) are key lipid mediators involved in immunity and bone remodelling. This study evaluates the inter-relationship between serum levels of S1P and S1PR and clinical activity, radiological findings and different stages of PsA. A cross-sectional observational study was conducted including 64 subjects: 21 healthy controls and 43 patients with PsA: 16 with recent-onset PsA and 27 with established PsA (EPsA). Clinical variables such as disease activity in PsA (DAPSA), bone mineral density (BMD), Trabecular Bone Score, 3D-Shaper and inflammatory activity by Doppler ultrasound and MRI were assessed. S1P and S1PR levels were measured by ELISA. S1P levels were significantly higher in the PsA group compared with controls (p=0.013), with the highest values observed in the EPsA subgroup (p=0.009). Although no significant correlation was observed with the DAPSA Score, S1PR levels were significantly higher in patients with Achilles enthesitis detected by ultrasound (p=0.046) and in those with bone proliferation/structural damage (p=0.03). Patients with EPsA showed significantly higher cortical volumetric BMD compared with controls (p=0.027). The S1P/S1PR axis is dysregulated in PsA and is associated with disease progression. Its correlation with ultrasound findings of enthesitis and new bone formation suggests that S1P acts as a critical mediator in the osteoimmunology of the enthesis, positioning it as a potential biomarker of structural damage and a novel therapeutic target.
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The increasing social, ethical and regulatory pressure on the use of vertebrates in bioscience research has promoted the development of alternative models. The use of invertebrate models is very common in basic research, where insects are used in many studies. Cockroaches such as Gromphadorhina portentosa have emerged as a promising model organism due to their ease of maintenance, breeding in laboratory conditions, longevity, physiological resilience, size, and ability to be manipulated for sample collection. Similarly, prior to 2010, the Periplaneta americana was widely used as a bioscience model and shares many of the attributes of the Gromphadorhina portentosa. The objective of our study was to carry out a review in which we described the biological characteristics and analyzed the application of cockroaches, and specifically Gromphadorhina portentosa, as an alternative model in bioscience research. To do so, we established the period from 2010 to 2025 to carry out the bibliographic search in international scientific databases, PubMed and Scopus, using only peer-reviewed scientific publications on cockroach applications in bioscience research. This review outlines the principal biological characteristics of cockroaches and evaluates their suitability as experimental models. Additionally, potential humane euthanasia methods are discussed. The most common applications of cockroaches in laboratory experimentation are described, and a critical analysis of their advantages and limitations as model organisms is presented. The analysis reveals significant potential for the use of cockroaches in preliminary and educational studies, as well as an opportunity to expand the diversity of species in scientific research, applying the principle of replacement of the use of animals in experimentation. The document highlights the need for protocol standardization and regulatory recognition for this species, offering an updated perspective on the state of the art regarding its rational incorporation into bioscience research.
Background/Objectives: Chronic non-specific low back pain is a leading cause of disability. Although therapeutic exercise and manual therapy are commonly recommended, their relative effects are often interpreted using broad therapeutic categories. This network meta-analysis aimed to compare the relative effectiveness of specific therapeutic exercise and manual therapy techniques on post-treatment self-reported disability in adults with chronic non-specific low back pain. Methods: A systematic review and frequentist random-effects network meta-analysis were conducted according to Cochrane recommendations and PRISMA-NMA guidance. The protocol was registered in PROSPERO (CRD42022331411). Randomized controlled trials including adults aged 18-65 years with chronic non-specific low back pain were searched in CENTRAL, PubMed, PEDro, Google Scholar, and SciELO up to 31 March 2026. Disability was assessed using the Roland-Morris Disability Questionnaire or Oswestry Disability Index. Effects were synthesized as standardized mean differences. Risk of bias was assessed with RoB 2, and confidence in network estimates was evaluated using CINeMA. Results: Forty-five studies were included. Compared with control/placebo, the largest favorable estimates were observed for equipment-based Pilates, stabilization with motor control, stabilization exercise, soft tissue manipulation, and Pilates Mat. Equipment-based Pilates showed the largest favorable estimate with moderate-confidence evidence, and soft tissue manipulation also showed moderate-confidence evidence. However, heterogeneity was substantial, and confidence in most favorable exercise estimates was low. Conclusions: Specific exercise and manual therapy techniques may reduce post-treatment disability in adults with chronic non-specific low back pain. Equipment-based Pilates and soft tissue manipulation showed favorable signals supported by moderate-confidence evidence. However, the findings do not support a definitive hierarchy of efficacy or categorical superiority of therapeutic exercise over manual therapy.
Pregnancy-associated breast cancer (PABC) is an aggressive malignancy affecting young women during gestation, lactation, or the post-weaning period. Despite its clinical significance and poor prognosis, how these physiological stages shape tumor biology remains poorly understood. Here, we integrate reproductive context with molecular and immune profiling to define shared and stage-specific features of PABC and uncover potential therapeutic vulnerabilities. We conducted BC360 NanoString gene expression analysis and CIBERSORTx immune deconvolution in 106 breast cancer cases, including 57 PABC patients stratified by diagnosis stage (gestation, breastfeeding, or post-weaning) and 49 non-PABC controls. Our study identified a shared aggressive signature across all PABC cases, marked by increased proliferation and impaired DNA repair. Notably, breastfeeding patients (PABC-BF) emerged as a distinct subset, displaying an immune-inflamed tumor profile characterized by elevated inflammatory chemokines, enriched CD8⁺ T-cell and regulatory T-cell infiltration, and prominent TIGIT inhibitory checkpoint upregulation. These findings reveal lactation as a physiological framework that shapes tumor immunity, defining a distinct tumor-immune landscape which warrants further investigation for potential therapeutic approaches.
We describe a case of Sweet syndrome, an acute neutrophilic dermatosis that may occur as a paraneoplastic manifestation. A 25-year-old man presented with recurrent abdominal pain and painful erythematous plaques on the trunk and upper limbs, without symptoms of catecholamine excess. Imaging revealed a retroperitoneal mass and extensive hypermetabolic lymphadenopathy on positron emission tomography/computed tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) and gallium-68 DOTA-Tyr3-octreotate (68Ga-DOTATATE), raising concern for metastatic disease. Skin biopsy confirmed Sweet syndrome, while lymph node biopsies demonstrated reactive lymphoid hyperplasia. A computed tomography-guided biopsy of the retroperitoneal mass established the diagnosis of paraganglioma, but was complicated by hypertensive crisis. Subsequent biochemical evaluation revealed markedly elevated plasma normetanephrine levels despite normotension. The patient underwent preoperative alpha-adrenergic blockade followed by surgical resection. Cutaneous lesions resolved rapidly after tumor removal, and plasma normetanephrines normalized, confirming biochemical cure. This case highlights an association between Sweet syndrome and succinate dehydrogenase complex iron-sulfur subunit B (SDHB)-related paraganglioma and underscores the risk of false-positive metastatic findings on functional imaging and reinforces the importance of biochemical exclusion of paraganglioma before biopsy of vascularized retroperitoneal masses.
Mutations in the innate immune adapter MYD88 occur selectively in Lymphoplasmacytic lymphoma (LPL) of the IgM/WM subtype and ABC type DLBCL. We used MYD88L265P mutation detection based on AS-PCR using genomic DNA extracted from FFPE tissue and correlated with histopathological subtype, phenotype, Cell of origin classification based on IHC, tumor site and genetic features in a large cohort of 249 small B cell lymphoma and 204 DLBCL samples. In DLBCL MYD88 L265P mutation is found in 32% of cases and it is significantly more prevalent in cases with the non-GCB phenotype (OR 5.78 p value = 2.07 × 10⁻⁵) and in DLBCL of extranodal locations (OR = 5.44 p value p < 0.001), including, not only immuneprivileged sites but also the skin, breast, upper respiratory tract, adrenal gland and bone and soft tissues. MYD88L265P mutation is highly specific of the non-GCB type DLBCL, likely reflecting MCD/C5 genetic features in a subset of non-GCB/ABC DLBCL.
Acinic cell carcinoma (ACC) is a malignant epithelial neoplasm characterized by serous acinar differentiation and is most described in the salivary glands of humans and domestic animals. In animals, ACC is rare and its occurrence in the nasal cavity of cats is exceptionally uncommon. This case describes the clinical presentation, gross pathological findings, histological features and immunohistochemical profile of a nasal acinic cell carcinoma in a 14-year-old domestic shorthair cat. The animal showed chronic unilateral nasal discharge and epiphora. Bacteriological culture of nasal secretions yielded Pasteurella spp. and despite antimicrobial therapy the clinical condition worsened. Post-mortem examination revealed a whitish mass destroying the nasal turbinates extending to the frontal sinus. Histologically, the tumor exhibited solid, microcystic and follicular growth patterns, with moderate cellular atypia and cytoplasmic PAS-positive granules. Immunohistochemical analysis demonstrated diffuse positivity for pan-cytokeratin, with differential expressions of cytokeratin 8 and S-100 protein depending on the growth pattern, while α-smooth muscle actin was negative in neoplastic cells. These findings are consistent with biphasic acinic cell carcinoma showing mixed acinar and ductal differentiation. There are scant histological and immunohistochemistry complete descriptions of nasal acinic cell carcinoma in the feline species. This case states the importance of considering this rare entity in the differential diagnosis of chronic unilateral nasal disease, particularly, in older cats.
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Brain metabolic dysregulation and insulin-related signaling are increasingly recognized as contributing factors in Alzheimer's disease (AD) pathogenesis, disrupting amyloid-beta (Aβ) proteostasis and exacerbating neuroinflammation, and synaptic failure. However, current therapies yield inconsistent results due to a singular focus on specific targets, bioavailability and safety risks. D-chiro-inositol (DCI) is a natural compound with insulin-mimetic properties that has previously shown promising anti-inflammatory and neuroprotective results. This study investigated the neuroprotective efficacy of DCI using a tripartite approach: physiologically relevant primary neurons derived from AppNL-G-F knock-in mice, human hAPPswe SH-SY5Y cells, and the aggressive 5xFAD mouse model of AD. Toxicity, pharmacokinetic and pharmacodynamic profiling established DCI's safety and its ability to acutely improve systemic glucose handling. In vitro, DCI enhanced basal AKT and insulin receptor activation and modulated glycogen synthase kinase-3 beta (GSK-3β) activation, a kinase linked to amyloid precursor protein (APP) processing. This modulation was accompanied by reduced secretion of toxic Aβ42 species, preservation of neuronal integrity as determined by MAP2 immunostaining, and decreased overall APP protein levels. In vivo, chronic oral DCI administration significantly reduced hippocampal amyloid burden and promoted a shift in microglia from a reactive to a surveilling phenotype, with stronger effects in females. Notably, while DCI resolved microglial reactivity, astrogliosis remained largely unaffected, suggesting a cell-specific immunometabolic mechanism. These improvements translated into rescued recognition memory and normalized disinhibited risk-assessment behavior, indicative of restored hippocampal function. Collectively, DCI acts as a multi-modal agent by modulating insulin-related signaling, downregulating amyloid burden and attenuating neuroinflammation, making it an orally bioavailable candidate for AD therapy.
Objectives: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is characterized by aggressive behavior, limited therapeutic options, and poor clinical outcomes. Due to the absence of hormone receptors and HER2 expression, systemic treatment relies predominantly on chemotherapy, which is associated with high rates of early recurrence and mortality. Emerging evidence suggests that alterations in the microbiome can contribute to TNBC progression and influence therapeutic response, particularly affecting the efficacy of chemotherapy and immunotherapy through immune-mediated mechanisms; however, its role in TNBC remains incompletely understood. This systematic review aims to explore the role of the microbiome in TNBC. It specifically aims to understand if the microbiome influences complete pathological response in TNBC. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed in PubMed and Cochrane databases. Fourteen eligible studies were included, encompassing preclinical and clinical evidence. Results: The findings indicate that both gut and tumor-associated microbiota significantly influence therapeutic response in TNBC, especially in the context of neoadjuvant chemotherapy (NACT) and immune checkpoint blockade (ICB). Higher microbial diversity and the presence of specific commensal taxa were consistently associated with enhanced antitumor immune activation, increased immune cell infiltration, and improved treatment efficacy. Conversely, antibiotic-induced dysbiosis was linked to reduced pCR rates and poorer clinical outcomes. Microbiome-modulating interventions demonstrated potential in restoring eubiosis and enhancing therapeutic responsiveness. Conclusions: Overall, the available evidence supports the microbiome as a promising biomarker and therapeutic target for optimizing treatment strategies and improving outcomes in TNBC.
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Limited understanding of African swine fever (ASF) immunity remains a major barrier to the rational development of safe and effective vaccines. While antibody-mediated protection is still poorly defined, growing evidence highlights a central role for cellular immunity, particularly cytotoxic cells, as components associated with ASF virus (ASFV) infection control. However, the contribution of individual cytotoxic subsets across different virological and immunological contexts is not well characterised. Here, we investigated cytotoxic responses during BA71ΔCD2 live attenuated vaccine-induced protection and during late-stage lethal ASFV infection. Protective immunity was characterised by antigen-specific cytotoxic T-cell responses, whereas acute ASF was associated with broad cytotoxic activation. Early increases in perforin-positive CD4-CD8αβ⁺ T cells coincided with the onset of protection, and elevated recall responses correlated with survival following lethal challenge, supporting their association with protective immunity. Additional correlates of protection included CD4⁺CD8αβ⁺ cytotoxic T cells, IFNγ-producing cells, and specific antibodies, illustrating the multifactorial nature of protective immunity. In contrast, pigs with acute ASF showed broad cytotoxic expansion, perforin-positive natural killer and γδ T cells showing the strongest association with viremia. Together, these findings advance our understanding of cytotoxic responses to ASFV and identify perforin-positive T cells, alongside complementary immune components, as potential correlates of protection for future vaccine development.