Tissue Pathology Research Articles

Unexpected Encounters: Ossifying Fibromyxoid Tumor Unveiled During Evaluation for Inguinal Hernia

Abstract Introduction/Objective Soft tissue pathology often presents diagnostic surprises, elucidating the intricate nature of disease processes. In this introduction, we discuss the unexpected discoveries that can arise during clinical evaluations and emphasize the importance of thorough evaluation in soft tissue pathology. Methods/Case Report We present the case of a 40-year-old male who underwent evaluation for a right inguinal hernia, during which an ossifying fibromyxoid tumor (OFMT) was incidentally discovered. Imaging modalities intended for hernia assessment revealed a 4.5 cm mass abutting the hernia site. Surgical exploration, initiated for hernia repair, unveiled the unsuspected coexistence of a direct inguinal hernia and an OFMT. Histopathological analysis of the excised mass revealed a complex OFMT architecture, characterized by a plexiform growth pattern, fibrous to fibromyxoid matrix, and distinct cellular features. The neoplastic cells exhibited bland round to ovoid nuclei, occasional multinucleation, and scattered mitotic figures. Immunohistochemistry demonstrated variable positivity for desmin and focal positivity for S-100 protein, while CD34, keratin AE1/AE3, smooth muscle actin, and p63 were consistently negative. Notably, the tumor exhibited areas of hypercellularity and easily identifiable mitotic figures, consistent with morphologic features of malignancy in OFMT. Results (if a Case Study enter NA) N/A Conclusion This case highlights the intricate interplay between primary clinical concerns and incidental pathological findings, underscoring the necessity for comprehensive evaluation in soft tissue pathology. Understanding the nuanced histological and immunohistochemical characteristics of OFMT is pivotal for accurate diagnosis and optimal patient management. The unexpected discovery of OFMT during evaluation for inguinal hernia emphasizes the importance of thorough assessment and consideration of incidental findings in clinical practice.

High-Resolution Terahertz Spectroscopy for MedicalDiagnostics.

The metabolomics-based approach to diagnostics and therapy monitoring is a fast-emerging trend in modern medicine. Terahertz nonstationary spectroscopy based on the induction and disintegration of freely decaying polarization in the gas mixture during the interaction of radiation with molecules at resonance frequencies is a high-sensitivity method for studying multicomponent gas mixtures, which is promising for identifying metabolites in the thermal decomposition products of biological samples. The paper presents the results of the application of high-resolution terahertz spectroscopy to the study of biological samples taken from patients with certain diseases (pathologically changed tissues of ear-nose-throat organs and similar pathologic tissues formed in other life support systems) to search for characteristic sets of metabolites characterizing the pathology. The world's first measurements of the spectra of pathologic samples of cysts, formed in different life support systems, were carried out, which made it possible to identify similar substances in tissues having the same pathology.

A review of label-free photonics-based techniques for cancer detection in the digestive and urinary systems

Abstract For a long time, it has been known that optics can provide a broad range of tools for addressing clinical needs, particularly diagnostics. Optical techniques can help in identifying diseases and detecting pathological tissues with non/minimally invasive and label-free methods. Given the current limitations of standard clinical procedures, such an approach could provide a powerful tool in detecting gastrointestinal and bladder cancers. However, each technique has serious limitations regarding one or more of the following features: biomarker sensitivity, penetration depth, acquisition times, or adaptation to the clinical environment. Hence there is an increasing need for approaches and instruments based on the concept of multimodality; in this regard, we review the application of different imaging/spectroscopy tools and methods operating in the first two optical windows (SHG, SPEF, TPEF, THG, 3PEF, CARS, Raman and reflectance) for tumour detection in the digestive and urinary systems. This article also explores the possibility of exploiting the third bio-tissue transmission window (1600-1900 nm) by reviewing state of the art in ultrafast laser sources development. Finally, we summarise the most recent results in developing multiphoton endoscopes – a key element for clinical in vivo translation of photonics-based diagnostics.

Development of a nanometre scale X-ray speckle-based CT technique through the 3-D histological assessment of an acute respiratory distress syndrome model

The study of biological soft tissue structures at the micron scale details the function of healthy and pathological tissues, which is vital in the diagnosis and treatment of diseases. Speckle based X-ray phase contrast tomographic scans at a nanometer scale have the potential to thoroughly analyse such tissues in a quantitative and qualitative manner. Diamond light source, the UKs national synchrotron facility developed and refined a 1-D X-ray speckle-based imaging technique, referred to as Fly scan mode. This novel image acquisition technique was used to perform a rapid structural composition scan of rodent lung histology samples. The rodent samples were taken from healthy and Staphylococcus aureus induced acute respiratory distress syndrome models. The analysis and cross comparison of the fly scan method, absorption-based tomography and conventional histopathology H&E staining microscopy are discussed in this paper. This analysis and cross comparison outline the ways the speckle-based technique can be of benefit. These advantages include improved soft tissue contrast, 3-D volumetric rendering, segmentation of specific gross tissue structures, quantitative analysis of gross tissue volume. A further advantage is the analysis of cellular distribution throughout the volumetric rendering of the tissue sample. The study also details the current limitations of this technique and points to ways in which future work on this imaging modality may progress.

Dual spatial host-bacterial gene expression in Mycobacterium abscessus respiratory infections

Co-localization of spatial transcriptome information of host and pathogen can revolutionize our understanding of microbial pathogenesis. Here, we aimed to demonstrate that customized bacterial probes can be successfully used to identify host-pathogen interactions in formalin-fixed-paraffin-embedded (FFPE) tissues by probe-based spatial transcriptomics technology. We analyzed the spatial gene expression of bacterial transcripts with the host transcriptomic profile in murine lung tissue chronically infected with Mycobacterium abscessus embedded in agar beads. Customized mycobacterial probes were designed for the constitutively expressed rpoB gene (an RNA polymerase β subunit) and the virulence factor precursor lsr2, modulated by oxidative stress. We found a correlation between the rpoB expression, bacterial abundance in the airways, and an increased expression of lsr2 virulence factor in lung tissue with high oxidative stress. Overall, we demonstrate the potential of dual bacterial and host gene expression assay in FFPE tissues, paving the way for the simultaneous detection of host and bacterial transcriptomes in pathological tissues.

7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week Phase 1/2 Open Label Study

Abstract Disclosure: K. Gunter: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. R.A. Wermers: Research Investigator; Self; Inozyme Pharma. R. Fuhr: Employee; Self; Parexel GmbH. Research Investigator; Self; Inozyme Pharma. D. Schnabel: Research Investigator; Self; Inozyme Pharma. A. Besancon: Research Investigator; Self; Inozyme Pharma. M.A. Nour: Research Investigator; Self; Inozyme Pharma. D. Wenkert: Stock Owner; Self; Inozyme Pharma. Y. Sabbagh: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene that result in low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization. Subsequent pathologic soft tissue calcification results in severe vascular calcification and ∼50% infant mortality. By early adolescence the majority of survivors develop FGF-23 mediated hypophosphatemic rickets, characterized by bone deformities, short stature, joint/ligament calcification and musculoskeletal pain. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical outcomes) of INZ-701 in adults with ENPP1 Deficiency through the end of the phase 2 study period (week 48). Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three adults in each of three dose cohorts (0.2, 0.6 and 1.8 mg/kg, total N=9) with genetic variants in ENPP1 and PPi <1300 nM (NCT04686175). Participants were dosed subcutaneously on Day 1, then twice weekly from Day 8 to end of study. Data through wk 48 as of July 6, 2023 are included; topline wk 48 data will be presented. Per protocol, participants may continue to receive INZ-701 beyond wk 48. Results: Rapid increase in mean PPi from baseline of 426±407 nM was noted in all patients, reaching the healthy volunteer range within 6 hrs of the first dose with sustained elevation through wk 48. Mean PPi across the 0.2, 0.6 and 1.8 mg/kg dose cohorts from day 32 to wk 48 was 1299±131 nM, 1356±136 nM, and 1282±81 nM, respectively. There were improvements from baseline to wk 48 in mean pooled FGF-23 (-22 pg/mL) and serum phosphate (+0.18 mg/dL), with dose-dependent changes in bone specific alkaline phosphatase consistent with bone healing. DEXA revealed improvements in spine BMD and BMC. There were trends towards improvement in mean % predicted change in 6MWT from baseline to wk 48: cohort 1, 76.7% (SE 10.5) to 85.0% (SE 3.0); cohort 2, 52.2% (SE 10.9 ) to 79.0% (SE 2.9); cohort 3, wk 48 data not available. Improvements were also observed in physician and patient global impression of change score (with no patients deteriorating) and PROMIS pain intensity score. INZ-701 was well tolerated with no drug-related serious or severe (> grade 2) adverse events. Low titers of non-neutralizing anti-drug antibodies (≤160) were observed in 7/9 patients. Long half-life of approximately 126 hours suggests the potential for once-weekly dosing. Conclusions: In adults with ENPP1 Deficiency, INZ-701 was well tolerated with no related serious or severe adverse events. INZ-701 demonstrated a rapid and sustained increase in PPi levels from baseline to week 48 with corresponding improvements in bone mineral biomarkers, functional performance, and patient and physician-reported outcomes. Presentation: 6/3/2024

Sodium Hydrosulfide Protects Rats from Hypobaric-Hypoxia-Induced Acute Lung Injury

Hydrogen sulfide (H2S), as a key gas signaling molecule, plays an important role in regulating various diseases, with appropriate concentrations providing antioxidative, anti-inflammatory, and anti-apoptotic effects. The specific role of H2S in acute hypoxic injury remains to be clarified. This study focuses on the H2S donor sodium hydrosulfide (NaHS) and explores its protective effects and mechanisms against acute hypoxic lung injury. First, various mouse hypoxia models were established to evaluate H2S’s protection in hypoxia tolerance. Next, a rat model of acute lung injury (ALI) induced by hypoxia at 6500 m above sea level for 72 h was created to assess H2S’s protective effects and mechanisms. Evaluation metrics included blood gas analysis, blood routine indicators, lung water content, and lung tissue pathology. Additionally, LC-MS/MS and bioinformatic analyses were combined in performing quantitative proteomics on lung tissues from the normoxic control group, the hypoxia model group, and the hypoxia model group with NaHS treatment to preliminarily explore the protective mechanisms of H2S. Further, enzyme-linked immunosorbent assays (ELISA) were used to measure oxidative stress markers and inflammatory factors in rat lung tissues. Lastly, Western blot analysis was performed to detect Nrf2, HO-1, P-NF-κB, NF-κB, HIF-1α, Bcl-2, and Bax proteins in lung tissues. Results showed that H2S exhibited significant anti-hypoxic effects in various hypoxia models, effectively modulating blood gas and blood routine indicators in ALI rats, reducing pulmonary edema, improving lung tissue pathology, and alleviating oxidative stress, inflammatory responses, and apoptosis levels.

Transcriptomic and Metabolomic Analyses Reveal the Attenuating Role of Cordycepin and Cordyceps militaris Extract on Acute Liver Injury Induced by LPS in Piglets.

Cordyceps militaris extract (CME) contains many bioactive compounds, mainly cordycepin (CPN). This study aimed to investigate the possible mechanisms underlying the amelioration of LPS-induced acute liver injury in piglets by CME or CPN supplementation using multi-omics analysis. Twenty-four weaned piglets were randomly distributed into 4 groups (n = 6): the control and LPS groups were fed basal diets; the CPN + LPS (CPN-LPS) and CME + LPS (CME-LPS) groups were fed the basal diets supplemented with CME or CPN. The results showed that CPN or CME supplementation significantly decreased the C-reactive protein level (p < 0.05) and improved liver tissue pathology to prevent acute liver injury after LPS treatment. Compared with LPS, the transcriptomic analysis indicated that CPN supplementation significantly downregulated cell adhesion molecules, while CME supplementation significantly downregulated inflammatory mediator regulation of TRP channels, complement and coagulation cascades and cytokine-cytokine receptor interaction. The metabolomic results showed that CPN or CME supplementation significantly reduced disease biomarker of bicyclo-prostaglandin E2, and increased levels of deoxyinosine and 3-hydroxyanthranilic acid (p < 0.05). The combined transcriptome and metabolome helped identify two metabolites PC 34:2 and PC 36:0, which may be associated with the restoration of liver cell morphology. In conclusion, CPN and CME could attenuate LPS-induced acute liver injury by regulating immune-related genes and metabolites. This study elucidates the potential protective mechanism of CPN or CME supplementation against acute liver injury.

The importance of histopathological diagnosis in assessing the impact on the prognosis of White Spot Disease in cultures of Pacific white shrimp (Penaeus vannamei)

Aquaculture is a globally relevant sector in terms of production and income. When we think about shrimp farming, Penaeus vannamei, the Pacific white shrimp, has been instrumental in this growth due to its characteristics and advances in production. Despite achievements, it faces significant economic challenges due to the white spot syndrome virus (WSSV), causing considerable losses. This virus has led to significant economic losses, affecting economies such as Ecuador's. The clinical signs of WSSV require rigorous diagnostic procedures, combining histopathological examination and PCR assays. A retrospective study of 900 specimens of Penaeus vannamei in Ecuador highlights the correlation between tissue pathology and mortality rates, enhancing understanding of the direct impact of the disease. Histopathological analysis reveals distinctive intracellular viral inclusions, reflecting disease progression. Although PCR assays provide definitive diagnoses, histopathological evaluation enriches understanding of lesion severity, supporting a comprehensive approach to disease management strategies.

Diminished circadian and ultradian rhythms of human brain activity in pathological tissue in vivo

Chronobiological rhythms, such as the circadian rhythm, have long been linked to neurological disorders, but it is currently unknown how pathological processes affect the expression of biological rhythms in the brain. Here, we use the unique opportunity of long-term, continuous intracranially recorded EEG from 38 patients (totalling 6338 hours) to delineate circadian (daily) and ultradian (minute to hourly) rhythms in different brain regions. We show that functional circadian and ultradian rhythms are diminished in pathological tissue, independent of regional variations. We further demonstrate that these diminished rhythms are persistent in time, regardless of load or occurrence of pathological events. These findings provide evidence that brain pathology is functionally associated with persistently diminished chronobiological rhythms in vivo in humans, independent of regional variations or pathological events. Future work interacting with, and restoring, these modulatory chronobiological rhythms may allow for novel therapies.

Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration

In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

An approach to determine pathological breast tissue samples with free‐space measurement method at 24 GHz

AbstractPathology is an important branch of science in the diagnosis and treatment of several diseases. In cancer diseases, serious investigations have been made about the course of the diseases. A report that is essential for both the patient and the doctor is prepared by the pathologists as a result of a detailed cellular examination. These reports contain information about the disease. Access duration to these reports, which affects the form and duration of the treatment, is extremely important today. It is possible to shorten this period with systems using antenna technologies. The pathological breast tissue samples have been examined by using horn antenna structures with high gain in this study. Dual identical horn antennas have been placed opposite each other as receivers and transmitters in the measurement setup at 24 GHz. Measurements of normal and cancerous breast tissues have been made, and the normalization process has been applied to the measured scattering parameters. The different values between normal and cancerous breast tissues have been shown with this process. The normalized values are compared with other analyzed values. According to the results obtained, the percentage of normalized values for transmission is much more effective and meaningful than other results.

Gross pathology and liver mercury concentrations in harbour porpoises, harbour seals and grey seals in Denmark, Northern Europe

Here we report the first investigation of gross pathology and mercury (Hg) in liver tissue from harbour porpoises, harbour seals and grey seals from Denmark, Northern Europe. Mercury concentrations ranged between 0.2 and 248 μg/g wet weight (ww) with highest concentrations found in grey seals and subadult harbour seals from the Baltic Sea, with no relationship to body condition. Necropsy findings across all three species decreasing in the following order: pneumonia (n = 60) > respiratory parasitism (n = 56) > wounds (n = 18) > GI-parasites (stomach nematodes and/or parasitic colitis) (n = 16) > ectoparasites (skin lice) (n = 12) > hepatic parasites/lesions (n = 8) > focal alopecia (n = 5) > nephropathy (n = 4) > middle ear complex parasites (n = 3) > nasal parasites (n = 2). Heart and/or lung worms were significantly highest in subadult harbour porpoises, GI parasites and nephropathy significantly lowest in subadult harbour seals and focal alopecia significantly highest in subadult harbour seals. Most cases of pneumonia were associated with respiratory parasites (68 %), while nine cases of wounds led to signs of septicaemia. Significant positive relationships were observed between Hg and the presence of respiratory parasites in subadult harbour porpoises and between Hg and the presence of focal alopecia, nephropathy, and gastrointestinal parasites in subadult harbour seals. Levels of Hg were in the categories for low risk (16–64 μg/g ww) in 18 %, moderate risk (64–83 μg/g ww) in 3 %, high risk (83–123 μg/g ww) in 2 % and severe risk (>123 μg/g ww) in 3 % of all individuals for health effects in marine mammals. In conclusion, using marine mammals as integrative sentinel species for Danish North Sea, Inner Danish Waters and the Baltic Sea ecosystems provides monitoring of ocean health in terms of multiple stressors such as anthropogenic contaminants and infectious diseases all being important in the context of global change.

Biofluorescence imaging system (BIS) Guided surgery for MRONJ: A Case Series on the Preservation of Teeth and Implants: Biofluorescence imaging system guided MRONJ surgery

The decision of surgical margin for Medication-Related Osteonecrosis of the Jaw (MRONJ) surgery is challenging. Recently, a method involving biofluorescence imaging system (BIS) has been reported for its application in MRONJ surgery to live detection of pathologic bone tissue from vital bone, which cannot be distinguished during conventional surgery. This case series aimed to assess the outcomes of adjacent teeth and implants near the lesion site in MRONJ patients who underwent BIS-guided MRONJ surgery. This retrospective study was assessed the radiographic and clinical outcomes of seven patients who underwent MRONJ surgery with BIS guidance but chose not to remove adjacent teeth or implants near the lesion. A total of seven patients (1 male, 6 females, 77.2 ± 4.7 years) were included in the study. Four implants and four teeth adjacent to the lesion were preserved. Over an average duration of 8.7 months, all subjects exhibited normal soft tissue healing and function without any complications. In conclusion, the BIS guided MRONJ surgery can be considered a minimally invasive and effective approach.

Tumeurs mésenchymateuses utérines associées à translocation : du nouveau sans oublier l’ancien. Une approche diagnostique intégrée

This review focuses on uterine mesenchymal tumors that are defined on a molecular level by a single and unique genetic alteration, that is somehow necessary and sufficient to allow tumor growth and progression. Although diverse from a clinical, morphological and immunohistochemical point of view, the different entities we are going to talk about share both a simple genomic profile with a low number of chromosomal alterations observed by CGH Array (few deletions, gains or amplifications...) and a low mutational burden observed by sequencing technics. Some of these entities are already well known and described in the literature when found outside of the uterus and gynecological tract. It remains intriguing that uterine mesenchymal pathology has been lagging behind when compared to its extrauterine counterpart. How can we explain that when it comes to inflammatory myofibroblastic tumors, abundant numbers of articles have been published since the 70's, but it was only in the early 2000s that the first relevant descriptions of this tumor in the uterus emerged? Certainly, the increased accuracy, availability, and use of molecular biology technics and in particular RNA sequencing in the area of uterine pathology can partly explain the reduction of the gap between soft tissue and uterine pathology we currently observe. Other reasons explaining this gap may be the high prevalence of smooth muscle tumors in the uterus and the abounding diversity of their morphological aspects, which may have partly eclipsed the array of differential diagnoses. Last but not least, one can hypothesize that the relative "simplicity" of hysterectomy procedures, referring to their safety and accessibility, has cured most of the lesions and partly clouded our knowledge regarding the biological potential and natural history of these newly described entities. As a consequence of this situation, our reader will often encounter the wording "uncertain malignant potential", as for some of these rare entities, evidence to establish reliable prognostic variables is still insufficient. We hope this review to be a useful tool to guide pathologists through the diversity and complexity of uterine mesenchymal tumors. As a scientific and medical community, sharing this knowledge will help us to collectively raise our vigilance and awareness by expanding the array of our differential diagnoses. We hope this will lead to more cases being accurately diagnosed, and ultimately, to a deeper knowledge regarding the biological potential and clinical evolution of these tumors. From a therapeutical point of view, the consequences of an accurate diagnosis for the patient are already appreciable through the use of targeted therapy. Examples include: ALK inhibitors in inflammatory myofibroblastic tumor, tyrosine-kinase inhibitors in COL1A::PDGFB rearranged sarcomas or mTOR inhibitors in PEComa.

Correlation Between Tumor Budding and Survivin Expression in Colorectal Cancer.

Correlation of Survivin expression levels in tumor tissues and degree of tumor outgrowth with colorectal cancer characteristics. The pathological tissues of 90 cases of colorectal cancer were observed by HE staining, and the tumor budding was judged by Ueno standard, and the expression of Survivin was detected by immunohistochemistry (IHC) technique (EnVision method), so as to analyze the correlation between tumor budding, the expression level of Survivin and the degree of tumor budding, and the correlation between the tumor budding and the patients' clinical characteristics. The expression level of Survivin was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer; tumor outgrowth was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer (P < 0.05); the expression level of Survivin was significantly correlated with the degree of tumor budding in patients with colorectal cancer (P < 0.05). In this paper, we tested the relationship between Survivin and tumor budding in colon cancer, and analyzed its relationship with clinicopathological features, with a view to providing a reference for the mechanism related to colorectal cancer.

Fusion model of gray level co-occurrence matrix and convolutional neural network faced for histopathological images.

The image recognition of cancer cells plays an important role in diagnosing and treating cancer. Deep learning is suitable for classifying histopathological images and providing auxiliary technology for cancer diagnosis. The convolutional neural network is employed in the classification of histopathological images; however, the model's accuracy may decrease along with the increase in network layers. Extracting appropriate image features is helpful for image classification. In this paper, different features of histopathological images are represented by extracting features of the gray co-occurrence matrix. These features are recombined into a 16 × 16 × 3 matrix to form an artificial image. The original image and the artificial image are fused by summing the softmax output. The histopathological images are divided into the training set, validation set, and testing set. Each training dataset consists of 1500 images, while the validation dataset and test dataset each consist of 500 images. The results indicate that the effectiveness of our fusion model is demonstrated through significant improvements in accuracy, precision, recall, and F1-score, with an average accuracy reaching 99.31%. This approach not only enhances the classification performance of tissue pathology images but also holds promise for advancing computer-aided diagnosis in cancer pathology.

Single-cell profiling reveals a conserved role for hypoxia-inducible factor signaling during human craniotomy infection.

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The importance of HIF signaling was validated using a mouse model of Staphylococcus aureus craniotomy infection, where HIF inhibition increases chemokine production and leukocyte recruitment, exacerbating tissue pathology. These findings establish conserved metabolic and transcriptional signatures that may represent promising future therapeutic targets for human craniotomy infection in the face of increasing antimicrobial resistance.

Silicon Phthalocyanines Functionalized with Axial Substituents Targeting PSMA: Synthesis and Preliminary Assessment of Their Potential for PhotoDynamic Therapy of Prostate Cancer.

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitor are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si-O-C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si-O-Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ΦF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(-) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.

Inhibition of Colon Cancer Xenograft Growth by Celecoxib Analog OSU-03013 Through Wnt/β-Catenin Pathway Modulation

OSU-03013 is a Celecoxib analog that dose not inhibit COX-2 expression. OSU-03013 effectively mimics the anti-tumor effects of Celecoxib, however, its exact mechanism in colon cancer (CC) is unknown. SW480 cells were injected subcutaneously into the axilla of nude mice until the volume of the transplanted tumor reached 80 mm3. SW480 cells were inoculated into the tail vein of nude mice to establish a liver metastasis model of CC. OSU-03013 was administered by gavage. The pathology of the tumor tissues was assessed using HE staining and cell apoptosis was measured using TUNEL staining. EMT markers in the tumors were determined using Western Blot, and IL-1β and TNF-α were determined using ELISA. VEGF-A and VEGFR-2 in tumor tissues were measured to assess angiogenesis using immunofluorescence. HE staining was conducted to detect the effect of OSU-03013 on liver metastasis. Western Blot assay was performed to determine the expression of Wnt2, β-catenin and GSK-3β. OSU-03013 reduced inflammatory cell infiltration and inhibited IL-1β and TNF-α production by modulating the Wnt/β-catenin pathway. OSU-03013 induced apoptosis of cancer cells in tumor tissues and possessed anti-angiogenic activity. OSU-03013 treatment reduced the number and size of metastatic nodules of cancer cells in liver tissues. OSU-03013 may inhibit tumor growth and angiogenesis through the Wnt3a/β-catenin pathway in CC nude mice.