Search Results (66)

Background/Objectives: Radiolabeled fibroblast activation protein inhibitors (FAPIs) are emerging as promising imaging agents assessing fibrotic diseases. This study evaluates [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for imaging pulmonary fibrosis in two mouse models, bleomycin-induced (BLM) and a transgenic (fra-2^tg) model, both displaying characteristics of human pulmonary fibrotic diseases. Methods: In the BLM model, C57BL/6 mice were treated with bleomycin or isotonic sodium chloride (controls) for 4, 5, and 6 weeks, followed by [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans. Fra-2^tg mice and wildtype (WT) littermates underwent at 7, 11, and 18/19 weeks of age a PET/CT scan. The selected timepoints correspond to early, middle, and late disease stages for each model. Imaging was complemented by ex vivo quantification, histological, and immunohistochemical (IHC) analyses. Results: In BLM mice, pulmonary [⁶⁸Ga]Ga-DATA^5m.SA.FAPi uptake showed a trend toward increase as early as 5 weeks of treatment compared with the controls, which was confirmed by ex vivo analysis (BLM: 3.31 ± 0.29%ID/g, n = 5; control: 1.61 ± 0.29%ID/g, n = 4; p = 0.0035). In fra-2^tg mice, no significant differences could be detected. IHC revealed elevated pulmonary FAP expression specifically at early (BLM) and mild (fra-2^tg) disease stages, whereas for BLM, tracer uptake was more pronounced at later stages. Conclusions: Our findings complement and extend observations from previous studies and support the potential of FAPI tracers as molecular imaging agents for pulmonary fibrosis. Full article

Background/Objectives: Pulmonary fibrosis is a progressive and fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for the non-invasive assessment of fibrotic activity. This study aimed to evaluate the diagnostic feasibility of [⁶⁸Ga]Ga-FAP inhibitor (FAPI) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) for imaging pulmonary fibrosis in a mouse model. Methods: A pulmonary fibrosis model was established by intratracheal administration of polyhexamethylene guanidine-phosphate (PHMG-p) to C57BL/6 mice. Fibrosis severity was quantified by the Ashcroft scoring system using hematoxylin and eosin and Masson’s trichrome staining and evaluated by computed tomography (CT) imaging at 7, 14, and 21 days after PHMG-p exposure. PET imaging was performed, and ex vivo biodistribution was assessed after injection of [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG. Results: Histological analysis and Ashcroft scoring revealed greater fibrosis severity in the PHMG-p-treated group. Western blot analysis demonstrated upregulation of FAP expression after PHMG-p exposure. CT showed increased mean lung density, while [⁶⁸Ga]Ga-FAPI-04 PET revealed significantly elevated pulmonary uptake of [⁶⁸Ga]Ga-FAPI-04 in the PHMG-p-treated group compared with the controls. [¹⁸F]FDG PET imaging also showed higher uptake of [¹⁸F]FDG in the PHMG-p-treated group than in the controls. Ex vivo biodistribution confirmed greater [⁶⁸Ga]Ga-FAPI-04 accumulation in the lungs of PHMG-p-treated mice. Conclusions: [⁶⁸Ga]Ga-FAPI-04 PET serves as a sensitive imaging biomarker for evaluation of fibrotic activity in PHMG-p-induced pulmonary fibrosis and complements [¹⁸F]FDG PET for assessing disease progression and therapeutic response. Full article

Introduction: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign proliferation of the melanin-producing retinal pigment epithelium (RPE). Although often a benign and incidental finding, multifocal CHRPE may mimic lesions associated with familial adenomatous polyposis (FAP). Case Description: We describe an 8-year-old girl presenting with optic disc pallor and widespread multifocal bear track CHRPE observed bilaterally on dilated fundoscopy. Fundus autofluorescence (FAF) imaging showed uniform areas of hypoautofluorescence corresponding to the bear track lesions. Spectral domain optical coherence tomography (SD-OCT) demonstrated normal lamination without atrophy. The full-field electroretinogram (ffERG) was within normal limits. Whole-genome sequencing (WGS) revealed a likely pathogenic heterozygous variant in the STAG2 gene (c.3222dup, p.Ser1075IlefsTer12). Conclusions: We present a rare case of bilateral, panretinal bear track CHRPE in a child with a likely pathogenic variant in STAG2. Using multimodal imaging, we contrast bear track lesions of the retina with FAP-associated CHRPE. We also present possible ophthalmic manifestations in carriers of pathogenic STAG2 variants. Full article

In the production process of the heavy oil industry, efficiently demulsifying water-in-heavy oil (W/HO) emulsions can effectively prevent the negative effects of emulsion corrosion on equipment, increase costs, reduce oil quality, and pollute the environment. Herein, polyether demulsifier complexes (PDC) were obtained by compounding fatty alcohol nonionic polyether (FAP) with perfluoropolyether (PFPEA, [CF₃O(CF₂CF₂O)_nCF₃]) through a simple physical blending method. The experimental results demonstrate that PDC exhibited outstanding demulsification performance for W/HO emulsions across varying temperatures: At 60 °C and 400 ppm dosage, PDC achieved complete dehydration (100%) within just 2 min, showing significantly faster demulsification kinetics compared to FAP and PFPEA. Even at the reduced temperature of 40 °C, PDC maintained effective demulsification capability, achieving complete phase separation within 6 min. These findings collectively establish PDC’s superior demulsification efficiency for W/HO emulsions, with particularly remarkable performance under challenging low-temperature conditions. Research on the demulsification mechanism indicates that PDC achieves efficient demulsification performance due to the synergistic effect the synergistic effect of FAP and PFPEA to effectively destroy the non-covalent bonds (hydrogen and π–π stacking) of interfacially active asphaltenes (IAA) at the oil–water interface, thereby achieving demulsification of W/HO emulsion. PDC with outstanding demulsification ability exhibits significant potential for practical applications in heavy crude oil–water emulsion treatment, and this work can provide insights for developing new composite demulsifiers for petroleum production. Full article

Melanoma is the most common type of skin cancer. Melanomas are well known for their ability to metastasize to other organs, including the lungs, liver, brain, and bones. The ability of melanoma cells to switch among different phenotypes is a key mechanism that underscores their metastatic potential. The objective of this work is to report here on the effect of calcium sulfide (CaS) dispersions in melanoma cells. Melanomas with the epithelial- and mesenchymal-like phenotypes were observed during cell culture preparation. The dose-dependent viability was explored up to slightly less than 3% per volume of cell culture. The dispersion reduced the relative percentage of melanomas with the epithelial- and mesenchymal-like phenotypes to (57 ± 5) and (55 ± 5)%, respectively, at 24 h post treatment. In contrast, the viability of normal fibroblasts treated with the dispersion or melanoma cells treated with the reactants used to prepare the dispersion remained nearly constant, with a value range of (100.0 ± 0.2)% for the control and (97 ± 4)% and (93 ± 2)% for doses as high as 2 and 3% per volume of cell culture, respectively. Fluorescence imaging measurements were consistent with the release of cytochrome c from the mitochondria and its translocation to the cell nuclei. The average expression of caspases 3 and 9 was found to be 3 and 1.4 times higher than in the corresponding melanoma control, respectively, which was consistent with intrinsic apoptosis. The response of vinculin expression was slightly different in both cell phenotypes. Vinculin was found to delocalize in the cytoplasm of treated mesenchymal melanoma cells, with a slightly higher concentration at the end of the actin fibers. A statistically significant increase (p < 0.0001) in the number of focal adhesion points (FAP) at the edge of the cell membrane–external cellular matrix (ECM) interphase was observed in post-treated melanoma that exhibited the epithelial-like phenotype. The changes in vinculin expression and FAP and the reduced viability of the melanomas were consistent with regulation of proteins associated with programmed cell death. It is thus proposed that the sulfides produced from the reactions of the nanoclusters in the acidic environment facilitate the regulation of proteins required to initiate apoptosis, although other processes may also be involved. We conclude that CaS may be an adequate chemical to selectively reduce melanoma viability with little effect on benign fibroblasts. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential of near-infrared photoimmunotherapy (NIR-PIT) targeting CAFs in PDAC. Methods: PDAC cells (Capan-1 and SUIT-2) and CAFs (hPSC-5) were used. Anti-human fibroblast activation protein (FAP)/podoplanin (PDPN) antibodies were used to bind to CAFs and conjugates with the specific photosensitizer IRDye^®700DX (IR700) to investigate the effects of NIR-PIT. Thereafter, BALB/c Slc-nu/nu mice were transplanted with Capan-1 and/or CAFs and treated with gemcitabine (GEM) with or without NIR-PIT. Results: The binding rate of anti-FAP antibody-AlexaFluor^®488 conjugate to hPSC-5 cells was high, whereas that of the anti-PDPN antibody-conjugate was not. The incubation of anti-FAP antibody-IR700 conjugate (αFAP-IR700) with hPSC-5 cells for 3 h led to maximal fluorescence on the surface of hPSC-5 cells. When NIR-PIT with αFAP-IR700 was performed in the co-culture group of Capan-1 and hPSC-5 cells, the proliferative capacity of Capan-1 cells decreased to the same level as that when Capan-1 cells were cultured alone (p < 0.05). In vivo, compared with the GEM group, the NIR-PIT with the GEM group showed a significant reduction in the tumor volume (day 28: 79 vs. 382 mm³, p < 0.05). Tumor volumes in the NIR-PIT group were not reduced compared with those in the control group. Conclusions: Combining NIR-PIT with conventional chemotherapy to target CAFs may enhance the anticancer effects on PDAC. Full article

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [⁶⁸Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients. Full article

This study aimed to optimize the ultrasound-assisted extraction (UAE) of polysaccharides from fermented Astragalus membranaceus (FAPS) and to investigate the physicochemical properties and antioxidant activities of the extracted polysaccharides. Using a combination of single-factor experiments and response surface methodology based on a Box–Behnken design, we improved the extraction of crude FAPS without deproteinization. Under optimal conditions (50 °C, 60 min, 8 mL/g, 480 W), the yield of crude FAPS obtained by UAE (7.35% ± 0.08) exceeded the yield from convectional hot water extraction (6.95% ± 0.24). After protein removal, the FAPS was subjected to comprehensive chemical analyses, including HPLC, HPGPC, FT-IR, UV spectroscopy, and a Congo red assay. The results showed that FAPS had a significantly higher carbohydrate content compared to the non-fermented group (95.38% ± 6.20% vs. 90.938% ± 3.80%), while the protein content was significantly lower than that of the non-fermented Astragalus polysaccharides (APS) group (1.26% ± 0.34% vs. 6.76% ± 0.87%). In addition, FAPS had a higher average molecular weight and a lower Mw/Mn ratio compared to APS. The primary monosaccharides in FAPS were identified as Glc, Ara, Gal and GalA, with a molar ratio of 379.72:13.26:7.75:6.78, and FAPS lacked a triple helix structure. In vitro, antioxidant assays showed that FAPS possessed superior antioxidant properties compared to APS. These results emphasize the significant potential of FAPS as an antioxidant, possibly superior to that of APS. The results of this study suggest that fermentation and UAE offer promising applications for the development and utilization of Astragalus membranaceus for human and animal health. Full article

WNT3A is an intestinal ligand triggering the Wnt/β-catenin (Wnt) pathway, which can be enhanced by R-spondin 1 (RSPO1) through the RSPO1–LGR axis or antagonized by the adenomatous polyposis coli (APC) protein supporting β-catenin-degradation. Wnt interplays with several pathways including PI3K/mTOR (mTOR). In this study, we evaluated the influence of WNT3A-commercial and home-made culture media and RSPO1 protein on the Wnt and mTOR interplay in non-APC and APC-mutated intestinal patient-derived organoids (PDOs). Normal mucosa (NM) of sporadic CRC and FAP PDOs were cultured with: WNT3A-lacking/containing commercial (A/A+B) or home-made (BASAL/WNT3A-conditioned medium (CM)±RSPO1) media. In non-APC-mutated-PDOs (CRC-NM), WNT3A-CM, over commercial A+B, strongly activated Wnt-target-genes CCND1 and c-MYC. Most importantly, the addition of RSPO1 to home-made WNT3A-CM or A+B led to the downregulation of the mTOR-downstream-effector phospho-S6 ribosomal protein (p-S6R), highlighting the activation of the RSPO1–pS6R in both non-APC (CRC-NM) and APC-mutated (FAP-NM) PDOs, independently from LGR5 gene expression modulation. Our work demonstrates that home-made WNT3A-CM strongly impacts the crosstalk between Wnt and mTOR over commercial media, and proposes RSPO1 as a key regulator of the RSPO1–p-S6R axis in both non-APC and APC-mutated PDOs. Together, these findings represent an important methodological guide for scientists working in these fields to select the most appropriate intestinal PDO media. Full article

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC. Full article

The aim of this in vitro study was to evaluate the effectiveness of highly concentrated fluoride products and remineralizing products (F-APC) in preventing erosive dental lesions in competitive swimming patients. A total of 48 teeth were extracted, preserved in saline solution and divided into three groups. In G1 (control group), each tooth was half-immersed in chlorinated pool water; in G2 (fluoride-treated group), after being totally immersed in chlorinated water, each tooth had half of its surface treated with a highly concentrated fluoride product once a week; in G3 (remineralization product-treated group), each tooth was totally immersed in chlorinated water and half of its surface was treated with a remineralizing product after each immersion. The study was conducted over a 4-week period, immersing the teeth for 4 h per day. In G1, statistically significant differences were observed in submerged versus non-submerged tooth surfaces at week 3 (T3) (p = 0.019) and week 4 (T4) (p = 0.0007), with four and eight surfaces showing erosive tooth wear (ETW), respectively. In G2, a difference was observed between fluoride-treated and non-fluoride-treated surfaces at T4 (p = 0.039), with three surfaces with ETW among the non-treated ones. In G3, the difference was observed between portions treated with F-APC and those not treated at T4 (p = 0.019), with four surfaces with ETW among the untreated ones. Chlorinated pool water is a potential erosive agent for teeth if water pH values reach a critical value. Treating the teeth surface with highly concentrated fluoride products, once a week for 5 min, and F-APC are effective in protecting teeth against tooth erosion. Full article

Background: Alveolar bone augmentation is a complex process influenced by a multitude of factors. The materials applied in augmentation procedures must be confirmed as non-toxic, and their physicochemical properties should allow proper bone reconstruction. The specifics of oral surgical procedures require the use of regenerative biomaterials with antimicrobial properties. This study focuses on the physicochemical characteristics of chosen nanosized biomaterials, as well as their cytotoxicity and antimicrobial properties. Methods: nanosized hydroxyapatite and fluorapatite (abbreviated as nHAp and nFAp) pellets were manufactured using a microwave hydrothermal synthesis method. The impact on Candida albicans, Streptococcus mutans, and Lactobacillus rhamnosus strains activity and adherence to apatites was tested. Cytotoxic evaluation was performed based on the differentiation process of MC3T3 cells. The effectiveness of MC3T3 differentiation was confirmed by Alizarin Red staining. Results: Contact with both biomaterials caused a reduction in the mean microbial count of S. mutans and C. albicans strains, as observed. Studied biomaterials demonstrated enhanced proliferation of MC3T3 cells, with the exception of the 1:1 nFAp concentration. Conclusions: Both biomaterials enhance the proliferation of fibroblasts and limit the activity of specific oral pathogens in vitro. The research clearly demonstrates the advantage of nFAp over nHAp, with a notable reduction in microbial count of Candida albicans and Streptococcus mutans over time. The lowest microbial count reduction was observed in the case of L. rhamnosus. Further research is required in order to fully understand the specifics of nHAp and nFAp antimicrobial action. However, the results were found to be more favourable for nFAp biomaterial. Full article

Carbon-based novel low-dimensional XC/YC (with X, Y ≡ Si, Ge, and Sn) heterostructures have recently gained considerable scientific and technological interest in the design of electronic devices for energy transport use in extreme environments. Despite many efforts made to understand the structural, electronic, and vibrational properties of XC and X_xY_1−xC alloys, no measurements exist for identifying the phonon characteristics of superlattices (SLs) by employing either an infrared and/or Raman scattering spectroscopy. In this work, we report the results of a systematic study to investigate the lattice dynamics of the ideal ${\left(\mathrm{X}\mathrm{C}\right)}_{\mathrm{m}}$/${\left(\mathrm{Y}\mathrm{C}\right)}_{\mathrm{n}}$ as well as graded ${\left(\mathrm{X}\mathrm{C}\right)}_{10-∆}/{\left({\mathrm{X}}_{0.5}{\mathrm{Y}}_{0.5}\mathrm{C}\right)}_{∆}/{\left(\mathrm{Y}\mathrm{C}\right)}_{10-∆}/{\left({\mathrm{X}}_{0.5}{\mathrm{Y}}_{0.5}\mathrm{C}\right)}_{∆}$ SLs by meticulously including the interfacial layer thickness $∆$ (≡1–3 monolayers). While the folded acoustic phonons (FAPs) are calculated using a Rytov model, the confined optical modes (COMs) and FAPs are described by adopting a modified linear-chain model. Although the simulations of low-energy dispersions for the FAPs indicated no significant changes by increasing $∆$, the results revealed, however, considerable “downward” shifts of high frequency COMs and “upward” shifts for the low energy optical modes. In the framework of a bond polarizability model, the calculated results of Raman scattering spectra for graded SLs are presented as a function of $∆.$ Special attention is paid to those modes in the middle of the frequency region, which offer strong contributions for enhancing the Raman intensity profiles. These simulated changes are linked to the localization of atomic displacements constrained either by the XC/YC or YC/XC unabrupt interfaces. We strongly feel that this study will encourage spectroscopists to perform Raman scattering measurements to check our theoretical conjectures. Full article

The rotational alignment of the femoral component in total knee arthroplasty (TKA) is considered an important factor, but it is still difficult to assess intraoperatively. This study was conducted to identify anatomical parameters for femoral rotational alignment. A total of 204 patients who underwent primary TKA between 2015 and 2019 were enrolled. The femoral lateral (FLAP) and femoral medial anteroposterior (FMAP) lengths were measured as the widest lengths in the anteroposterior (AP) axis after distal femoral resection. The difference between FLAP and FMAP was defined as dFAP. The concordance correlation coefficient (CCC) was assessed for agreement between the cTEA-PCA and the value of femoral rotation using the linear regression analysis equation. HKA, FLAP, FMAP, and dFAP were significantly associated with femoral rotational alignment. The prediction equation combining the novel intraoperative anatomical references showed improved association with rotational alignment. If dFAP was 6.0 mm, the femoral rotation angle was calculated as 4.9° using this univariate regression equation. The CCC was 0.483, indicating moderate agreement. The dFAP showed an association with distal femoral rotational alignment. A 6 mm dFAP could be a reference for around 5° of femoral rotation. The equation developed in this study may be a reliable tool for intraoperative distal femoral rotational alignment. Full article

Purpose: This study aimed to evaluate the feasibility of using [⁶⁸Ga]-fibroblast-activating protein inhibitor (FAPI) positron emission tomography (PET) imaging for diagnosing pulmonary fibrosis in a mouse model. We also examined its value in monitoring treatment response and compared it with traditional [¹⁸F]-fluorodeoxyglucose (FDG) PET and computed tomography (CT) imaging. Methods: A model of idiopathic pulmonary fibrosis was established using intratracheal injection of bleomycin (BLM, 2 mg/kg) into C57BL/6 male mice. For the treatment of IPF, a daily oral dose of 400 mg/kg/day of pirfenidone was administered from 9 to 28 days after the establishment of the model. Disease progression and treatment efficacy were assessed at different stages of the disease every week for four weeks using CT, [¹⁸F]FDG PET, and [⁶⁸Ga]FAPI PET (baseline imaging performed at week 0). Mice were sacrificed and lung tissues were harvested for hematoxylin-eosin staining, picrosirius red staining, and immunohistochemical staining for glucose transporter 1 (GLUT1) and FAP. Expression levels of GLUT1 and FAP in pathological sections were quantified. Correlations between imaging parameters and pathological quantitative values were analyzed. Results: CT, [¹⁸F]FDG PET and [⁶⁸Ga]FAPI PET revealed anatomical and functional changes in the lung that reflected progression of pulmonary fibrosis. In untreated mice with pulmonary fibrosis, lung uptake of [¹⁸F]FDG peaked on day 14, while [⁶⁸Ga]FAPI uptake and mean lung density peaked on day 21. In mice treated with pirfenidone, mean lung density and lung uptake of both PET tracers decreased. Mean lung density, [¹⁸F]FDG uptake, and [⁶⁸Ga]FAPI uptake correlated well with quantitative values of picrosirius red staining, GLUT1 expression, and FAP expression, respectively. Conclusions: Although traditional CT and [¹⁸F]FDG PET reflect anatomical and metabolic status in fibrotic lung, [⁶⁸Ga]FAPI PET provides a means of evaluating fibrosis progression and monitoring treatment response. Full article