Search Results (4,058)

Splenic nodules in dogs that were historically classified under the broad term “fibrohistiocytic nodules” are now recognised as distinct entities within likely a biological continuum. These include lymphoid hyperplasia extending to indolent lymphoma and complex hyperplasia to stromal sarcoma. However, the molecular mechanisms underpinning these proposed progressions remain largely unexplored, particularly at the genomic and transcriptomic levels. This study aimed to delineate and compare the transcriptomic landscapes of four distinct canine splenic nodules through differential gene expression profiling. RNA sequencing was performed on twelve formalin-fixed, paraffin-embedded (FFPE) splenic tissue samples obtained from dogs diagnosed with lymphoid hyperplasia, complex hyperplasia, histiocytic sarcoma, and stromal sarcoma, with normal canine spleen serving as a control tissue. Comparative transcriptomic analysis identified 47 differentially expressed genes (DEGs) between splenic nodules and normal spleen, including CSRP1, SLC40A1, C1QA, C1QC, DLA-12, FTL, FXYD6, MPEG1, OAS3, CSF1, and JMJD6. Furthermore, 39 DEGs were significantly altered among the four splenic lesion types, such as MLC1, ERAS, MOV10L1, LOC102152143, COL4A1, COL4A2, COL12A1, NOTCH3, PLOD2, CPXM2, MRC1, GALNT5, TIMP1, and TFPI2. Many of these genes have previously been implicated in tumorigenesis and metastasis in other malignancies. These findings suggest that dysregulated gene expression may contribute to the activation of stromal cells and macrophages within the spleen, facilitating malignant transformation. Overall, these findings deliver novel transcriptomic insights into canine splenic tumorigenesis that may improve diagnostic precision, inform prognostic assessment, and support the development of targeted therapeutic strategies in veterinary oncology. Full article

This study examined the effects of applying silver nanoparticles (AgNPs; 0, 5 and 10 mg L⁻¹) in a hydroponic system for seven days on growth parameters and on nutrient and phytohormone concentrations in two tomato cultivars, Vengador and Rio Grande. The results indicated that AgNPs at concentrations of 5 and 10 mg L⁻¹ did not change leaf number, stem length, or fresh/dry biomass weight. In leaves of Vengador, P and K concentrations decreased, while Mg and S increased in response to AgNPs. In stems and roots, both P and K decreased. Zn concentrations increased in leaves, Mn in stems and roots. In leaves of Rio Grande, K, Mg, S, Cu and Mn concentrations increased, while P decreased in AgNP-treated plants, as compared to the control. In stems, N, S and Mn concentrations increased, but P, K, Ca, Mg and B decreased. In roots, P, K, Ca, Mg, Cu, Zn, Mn and B decreased, whereas S increased. Silver was only detected in roots of plants treated with AgNPs in both cultivars under study. In leaves of Rio Grande plants, kinetin concentrations decreased with AgNPs applications. In roots of Vengador, indole-acetic acid concentrations increased with 10 mg AgNP L⁻¹; in Rio Grande, roots exhibited an increased concentration of gibberellic acid and abscisic acid in plants exposed to 5 mg AgNP L⁻¹. The evidence retrieved from this work unveils the impact of metal-based NMs on the modulation of nutrient and phytohormone concentrations in a so important food crop such as tomato. Full article

Control of process-related impurities is of critical importance for developing an efficient and suitable synthetic process of an active pharmaceutical ingredient. In the study of a key intermediate of silodosin (KIS), two process-related impurities including the benzaldehyde impurity (BAI) and indole impurity (IDI) were prepared and fully characterized to determine their downstream fate. Under optimized conditions, BAI was formed in a yield of ~48% by treating KIS with 10% hydrogen peroxide at 60 °C. Interestingly, BAI would not be expected to be the major product under the apparent Baeyer–Villiger oxidative condition. Furthermore, by adding 20 mM FeCl₃ into the above 10% hydrogen peroxide solution, IDI became the major product in a yield of ~43% under this Fenton reaction-like condition. The probable formation mechanism of IDI was discussed and validated in the context of certain structurally similar substrates. Full article

Microbiota-derived indoles and short-chain fatty acids (SCFAs) modulate intestinal immunity via the aryl hydrocarbon receptor (AhR) and vitamin D receptor (VDR). This review proposes an operational AhR–VDR axis—three testable models (sequential, parallel, reciprocal)—to explain how indoles (AhR) and SCFAs/vitamin D (VDR) may cooperate to drive IL-22–mediated repair, antimicrobial peptide production, autophagy, and tight-junction restoration. We critically evaluate prebiotics, probiotics, and postbiotics: prebiotics shift fermentation toward SCFAs but show context-dependent effects; probiotics can supply indole-type AhR ligands yet are strain-specific; postbiotics offer standardized ligand delivery but face formulation challenges. We distinguish Salmonella-specific findings (e.g., SCFA suppression of SPI-1) from general colitis data and prioritize molecular validation, temporal mapping, multi-omics responder stratification, and standardized postbiotic development for clinical translation. Full article

Background/Objectives: The ratio of percentage of prostate cancer (PCa) biopsy-positive cores (BPC) to prostate volume as the index density factor (Id-BPC) was used to predict the risk of high tumour grades in the surgical specimens of European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. Methods: From January 2013 to December 2021, we evaluated 651 patients without any prior treatment for PCa. In the surgical specimen, tumour grades were classified as indolent (International Society of Urological Pathologists Classification (ISUP) 1), significant (ISUP 2/3), and lethal (ISUP 4/5). Associations with the risk of significant and lethal cancers were assessed by the multinomial logistic regression model. Results: Tumour grade was clinically significant (ISUP 2/3) in 522 (80.2%) cases and lethal (ISUP 4/5) in 99 (15.2%), while the results were not significant (ISUP 1) in 30 (4.6%) subjects. The association of Id-BPC was always stronger than BPC for ISUP 1 vs. 4/5 (OR = 0.284; 95% CI: 0.128–0.632; p = 0.002), ISUP 2/3 vs. 4/5 (OR = 0.744; 95% CI: 0.586–0.946; p = 0.016), and ISUP 1 vs. 2/3 (OR = 0.382; 95% CI: 0.176–0.828; p = 0.015), and this trend held after adjusting for clinical factors. Conclusions: Accordingly, Id-BPC was positively associated with lethal disease, as, when it increased or decreased, it was more or less likely, respectively, to find ISUP 4/5 in the surgical specimens of the operated subjects, who could have been stratified according to Id-BPC risk levels. Full article

Background: Follicular lymphoma (FL) is the second most common B-cell lymphoma in Western countries, typically presenting as an indolent disease with prolonged overall survival. Despite favorable initial responses to therapy, most patients experience relapse, and early progression is associated with poor outcomes. Methods: This guideline provides evidence-based recommendations from the Spanish GELTAMO group on the diagnosis, staging, treatment, and follow-up of FL. A systematic literature review was conducted, and recommendations were graded according to the GRADE system. Results: Histopathological diagnosis should be based on excisional biopsy. PET-CT is recommended for staging and response evaluation. For localized disease, involved-site radiotherapy (ISRT) remains the treatment of choice. In asymptomatic patients with advanced-stage disease and low tumor burden, a watch-and-wait approach is appropriate, although rituximab monotherapy is also acceptable. For advanced-stage disease with high tumor burden, immunochemotherapy with anti-CD20 antibodies (rituximab or obinutuzumab) combined with CHOP, CVP, or bendamustine is recommended, followed by maintenance therapy. Management of relapsed disease is tailored based on tumor burden, treatment history, and timing of relapse. Although novel immunotherapies (CAR-T therapy and bispecific antibodies) are emerging as promising options, autologous stem cell therapies may still be a valid option in young patients with early relapse who are sensitive to immunochemotherapy. Conclusions: FL is a heterogeneous disease requiring individualized management strategies. Recent advances in immunotherapy and molecular diagnostics are reshaping the therapeutic landscape. These updated GELTAMO recommendations aim to provide practical guidance for optimal FL management in clinical practice. Full article

Background and Clinical Significance: Acute promyelocytic leukemia (APL) is a rapidly progressive subtype of acute myeloid leukemia defined by PML::RARA fusion and characterized by life-threatening coagulopathy. Because the disease typically follows an aggressive course, immediate treatment is essential once APL is suspected. This case report describes an atypical de novo presentation marked by indolent progression rather than the expected aggressive trajectory. Case Presentation: A 37-year-old female exhibited gradually declining white blood cell and neutrophil counts over the course of a year, followed by unexplained pancytopenia with severe neutropenia (0.1 × 10⁹/L). Evaluation for nutritional deficiencies and autoimmune disease was unrevealing aside from a positive ANA without clinical features of autoimmunity. Bone-marrow biopsy demonstrated morphologic and flow cytometric findings suggestive of APL, low-level t(15;17), PML::RARA fusion, and concomitant TP53 loss and ETV6 mutation. Despite the indolent clinical presentation and low disease burden, the molecular and cytogenetic findings confirmed the diagnosis of classical APL with TP53 loss and ETV6 mutation. Induction therapy with all-trans-retinoic acid and arsenic trioxide resulted in hematologic remission. Conclusions: This case highlights an unusually indolent form of de novo APL not previously documented in the literature, expanding the recognized clinical spectrum of the disease. The findings emphasize the importance of still considering severe diagnoses, such as APL, when presentations deviate from classical patterns. Atypical clinical trajectories should prompt careful assessment of marrow morphology and immunophenotypic features. Continued characterization of such cases may refine diagnostic criteria and direct individualized approaches to therapy. Full article

Background/Objectives: First row transition metal ions have recently regained attention in coordination chemistry as alternatives to gadolinium-based paramagnetic contrast agents, motivated by emerging safety concerns associated with certain Gd³⁺-based contrast agents. In this study, we report the development of a novel homoleptic diketonate Fe³⁺ complex functionalized with biocompatible indole moieties. We investigate its potential as a paramagnetic relaxation agent by evaluating its ability to modulate the T₁ and T₂ relaxation times of water proton. Methods: Iron(III) tris-1,3-(1-methylindol-3-yl)propanedionate [Fe(BIP)₃] was synthesized via a thermal method from bis(1-methylindol-3-yl)-1,3-propanedione (HBIP) using Fe(ClO₄)₃∙6 H₂O as the metal source. The complex was characterized by UV-Vis, IR and NMR spectroscopy, differential scanning calorimetry–thermogravimetric analysis, and single-crystal X-ray diffraction. Fe(BIP)₃ aggregation behavior in aqueous environment, including size and morphology of aggregates, was investigated using dynamic light scattering and scanning electron microscopy. Incorporation of the aggregates into phospholipid vesicles was evaluated by fluorescence resonance energy transfer and fluorescence correlation spectroscopy. The paramagnetic properties of monomeric Fe(BIP)₃ were probed in solution by nuclear magnetic resonance recurring to the Evans bulk magnetization method. Results: The designed synthetic procedure successfully afforded Fe(BIP)₃, which was fully characterized by UV-Vis and IR spectroscopy, as well as single-crystal X-ray diffraction. Aqueous solutions of Fe(BIP)₃ spontaneously formed rice-grain-shaped nanoscale aggregates of hydrodynamic radius ≈ 30 nm. Incorporation of these aggregates into phospholipid vesicles enhanced their stability. The longitudinal r₁ and transverse r₂ relaxivities of Fe(BIP)₃ aggregates were assessed to be 1.92 and 52.3 mM⁻¹s⁻¹, respectively, revealing their potential as paramagnetic relaxation agents. Conclusions: Fe(BIP)₃ aggregates, stabilized through incorporation into phospholipid vesicles, demonstrate promising potential as novel paramagnetic relaxation agents in aqueous environments. Full article

Identifying plant-growth-promoting rhizobacteria tolerant to saline–alkali conditions is critical for developing effective microbial agents and multi-strategy approaches to remediate saline–alkali soil. Two salt–alkali-tolerant bacterial strains—phosphorus-solubilizing Bacillus pumilus JL-C and cellulose-decomposing B. halotolerans XW-3—were isolated from saline–alkali soil, with both exhibiting multiple plant-growth-promoting properties, including nitrogen fixation and the generation of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylate deaminase. Alfalfa pot experiments were conducted under four treatments: a control, the strain JL-C treatment, the strain XW-3 treatment, and a co-inoculation treatment (JL-C/XW-3), all mixed with corn straw and applied to the saline–alkali soil. The results demonstrated that the co-inoculation treatment yielded the most significant growth-promoting effects on alfalfa, showing enhanced antioxidant enzyme activities; increased contents of proline, soluble sugar, and protein; reduced malondialdehyde content; lowered pH and electrical conductivity; elevated activities of key enzymes; and increased levels of available nitrogen, phosphorus, potassium, and organic matter content in the soil. The pot experiments were confirmed by field experiments. The results of 16S rRNA high-throughput sequencing revealed changes in the bacterial community composition in the alfalfa rhizosphere, showing shifts in the relative abundance of several bacterial taxa often reported as plant-associated or potentially beneficial. This study establishes a combined remediation strategy for saline–alkali soil utilizing complex microbial agents and corn straw. Full article

Giardiasis, caused by the protozoan parasite Giardia lamblia, remains a prevalent intestinal infection worldwide and a growing concern due to increasing resistance to nitroimidazole drugs. This study proposes an alternative therapeutic strategy by targeting fructose-1,6-bisphosphate aldolase (FBPA), a key glycolytic enzyme of the parasite, through structure-based virtual screening. A curated library of microbiome-derived metabolites was computationally evaluated and compared with clinically used antigiardial drugs. Several indole-based compounds exhibited favorable binding affinities and stable interactions within the catalytic pocket of FBPA. These findings suggest that microbiome metabolites could serve as promising scaffolds for the rational design of new antiparasitic agents. Overall, the study highlights the potential of integrating metabolic and computational approaches to identify next-generation therapeutics against giardiasis. Full article

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles. Full article

The excessive use of chemical fertilizers raised concerns regarding environmental sustainability and soil degradation, prompting increasing interest in biofertilizers as eco-friendly alternatives. Among these, a compound that is effective in stimulating root and plant growth is indole-3-acetic acid (IAA). In our study, we evaluated IAA production by the halotolerant bacterium Vreelandella titanicae under different and varying nutritional conditions, such as tryptophan availability, temperature, pH, salinity, etc. The bacterium showed significant IAA production under a broad range of conditions and a dependence on the presence of tryptophan for IAA biosynthesis. High salinity (1.0 M NaCl), slightly alkaline pH (8.0–9.0), and temperatures of 34 °C increased IAA production, while optimal growth occurred in the absence of NaCl at a range of temperatures of 25–28 °C, suggesting a stress-responsive regulation of its biosynthesis. Easily metabolizable carbon sources, such as glucose and mannitol, enhanced IAA yield again, whereas additions of 1.0 g L⁻¹ NH₄NO₃ and KH₂PO₄ in the basal medium, poor in these salts, inhibited both the growth of the bacterium and IAA production. Notably, V. titanicae produced relevant amounts of IAA in seawater (24.57 ± 11.28 μg⋅mL⁻¹) when used as growth medium and dairy whey (15.68 ± 2.42 μg⋅mL⁻¹), highlighting its suitability for low-cost and circular bioprocessing strategies. In conclusion, V. titanicae is a promising Plant Growth-Promoting Rhizobacterium (PGPR) candidate for sustainable IAA production and potential application in saline or marginal agricultural soils. Its ability to synthesize IAA in different growth media could allow its exploitation in environmentally friendly bioprocesses. Full article

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies. Full article

Reproductive performance in livestock and poultry is a core determinant of economic efficiency in the animal industry. While traditional research has primarily focused on genetics, endocrinology, and immune regulation, emerging microbiome studies reveal that commensal microbiota within the gut and reproductive tracts play an underestimated yet pivotal role in host reproductive health. This review systematically synthesizes recent advances regarding the relationship between the microbiome and reproductive functions in major livestock species (cattle, pigs, sheep, and chickens). We first delineate the theoretical basis and mechanisms of the “gut-reproductive axis,” highlighting cross-system communication mediated by microbial metabolites, including short-chain fatty acids (SCFAs), indoles, and bile acids. Subsequently, we provide an in-depth comparative analysis of the microecological features of both female (vagina/uterus) and male (semen/epididymis) reproductive systems, examining their impacts on fertility, sperm quality, and pregnancy outcomes. Furthermore, we explore the molecular and systemic mechanisms governing microbial regulation of reproduction, encompassing the modulation of the hypothalamic-pituitary-gonadal (HPG) axis, the balance of local mucosal immunity and inflammation, and epigenetic regulation. Finally, we address current challenges—such as causal validation and the scarcity of multi-species databases—and propose future directions, including spatial multi-omics, AI-integrated analysis, and microbial intervention strategies. Ultimately, this review aims to offer a theoretical foundation and translational insights for elucidating reproductive regulatory networks and developing microbiome-driven precision strategies to enhance reproductive performance. Full article

Brachiaria decumbens is a high-yielding forage grass of major economic value in tropical regions. The root endophytic fungus Piriformospora indica is widely recognized for promoting plant growth and stress tolerance, yet its effects on B. decumbens remain poorly characterized. Here, we profiled root responses to P. indica colonization at 10 days after inoculation (dais; early stage) and 20 dais (late stage) during symbiosis establishment. Colonization was confirmed by phenotypic and physiological assessments, with inoculated plants showing enhanced root growth; colonized roots exhibited higher activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), along with increased indole-3-acetic acid (IAA) levels, whereas malondialdehyde (MDA), jasmonic acid (JA), and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) were reduced. Transcriptome and metabolomic profiling identified 1884 and 1077 differentially expressed genes (DEGs) and 2098 and 1509 differentially accumulated metabolites (DAMs) at 10 dais (Pi10d vs. CK10d) and 20 dais (Pi20d vs. CK20d), respectively, and 3355 DEGs and 2314 DAMs between stages (Pi20d vs. Pi10d). Functional enrichment highlighted key pathways related to secondary metabolism, carbohydrate metabolism, and lipid biosynthesis. Differentially expressed transcription factors spanned multiple families, including MYB, AP2/ERF, MADS-box, and bZIP, consistent with broad transcriptional reprogramming during symbiosis establishment. Integrative multi-omics analysis further highlighted phenylpropanoid biosynthesis and α-linolenic acid metabolism as consistently co-enriched pathways, suggesting coordinated shifts in gene expression and metabolite accumulation across colonization stages. Collectively, these results provide a multi-layered resource and a framework for mechanistic dissection of the P. indica–B. decumbens interaction. Full article