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Acta Biochimica Et Biophysica Sinica Jun 2024N-glycans play important roles in a variety of biological processes. In recent years, analytical technologies with high resolution and sensitivity have advanced...
N-glycans play important roles in a variety of biological processes. In recent years, analytical technologies with high resolution and sensitivity have advanced exponentially, enabling analysts to investigate N-glycomic changes in different states. Specific glycan and glycosylation signatures have been identified in multiple diseases, including cancer, autoimmune diseases, nervous system disorders, and metabolic and cardiovascular diseases. These glycans demonstrate comparable or superior indicating capability in disease diagnosis and prognosis over routine biomarkers. Moreover, synchronous glycan alterations concurrent with disease initiation and progression provide novel insights into pathogenetic mechanisms and potential treatment targets. This review elucidates the biological significance of N-glycans, compares the existing glycomic technologies, and delineates the clinical performance of N-glycans across a range of diseases.
PubMed: 38910518
DOI: 10.3724/abbs.2024101 -
Journal of Nanobiotechnology Jun 2024Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples... (Review)
Review
Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level.
Topics: Humans; Microscopy, Fluorescence; Erythrocytes; Animals; Blood Platelets; Blood Cells; Hematology; Nanotechnology; Leukocytes
PubMed: 38910248
DOI: 10.1186/s12951-024-02605-2 -
EJNMMI Reports Jun 2024A physiological increase in the uptake of [Ga]Ga-labeled somatostatin analogues ([Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and...
Increased [Ga]Ga-SST uptake in the uncinate pancreatic process in new digital PET/CT machine and potential association with clinical and histologic factors in NET patients.
INTRODUCTION
A physiological increase in the uptake of [Ga]Ga-labeled somatostatin analogues ([Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and might be even higher in latest generation of PET/CT scanners and might be falsely interpreted as NET. We aimed to investigate the uptake of UP in a large population of NET patients who underwent [Ga]Ga-SST PET/CT with digital SiPM detectors. We also explored potential associations between UP uptake and various clinical, imaging, and pathological factors routinely assessed in NET patients.
METHODS
We analyzed all consecutive NET patients from July 2018 to June 2022 in this retrospective, single-center study. All patients underwent a [Ga]Ga-SST PET/CT scan on a digital SiPM PET/CT scanner. On visual analysis, we distinguished between normal linear and homogenous UP uptake or abnormal if otherwise. We compared SUV in patients with normal UP uptake to those with abnormal UP uptake with suspicious NET lesions on contrast-enhanced CT (ce-CT) and according to the site of the primary NET (pancreatic NET vs. other), patient gender (female vs. male) and tumor grade (grade 1-2 vs. 3) using a Mann-Whitney test. We also assessed the correlation between SUV values in UP with patients' age, primary NET Ki-67 counting, and its SUV, TLA and MTV values.
RESULTS
We included 131 NET patients with a total of 34 [Ga]Ga-DOTATATE PET/CT and 113 [Ga]Ga-DOTATOC PET/CT scans. An abnormal UP uptake was seen in 32 patients with 65.7% of suspicious NET lesion or extrinsic compression on morphological imaging. Normal UP uptake SUV were measured in 115 [Ga]Ga-SST scans (78.2%) with normal UP uptake and without suspicious lesion on morphological imaging. We found an average SUV of 12.3 ± 4.1 for [Ga]Ga-DOTATATE and 19.8 ± 9.8 g/ml for [Ga]Ga-DOTATOC, hence higher than those reported in the literature [SUVmax 5 ± 1.6 to 12.6 ± 2.2 g/ml] with significant difference with abnormal UP uptake and between both PET tracers (both p < 0.01). Significant results were a higher UP uptake on [Ga]Ga-DOTATOC in male patients (p = 0.02) and significant associations between UP uptake on [Ga]Ga-DOTATOC and SUV of the primary tumor (ρ [0.337-0.363]; p [0.01-0.02]).
CONCLUSION
We confirmed a higher and very frequent UP uptake in latest SiPM-detector [Ga]Ga-SST PET/CT with an even higher uptake in patients that had [Ga]Ga-DOTATOC PET/CT. SUV were significantly higher in abnormal UP uptake but there were overlaps with UP SUV values for both [Ga]Ga-SST and a correlation to morphological imaging is crucial. Besides, significant associations between UP uptake and SUV of the primary NET as well as patients' gender were seen in the larger cohort of [Ga]Ga-DOTATOC patients suggesting that both physiological and pathological parameters could affect UP uptake.
PubMed: 38910232
DOI: 10.1186/s41824-024-00203-x -
Scientific Reports Jun 2024Transjugular intrahepatic portosystemic shunt (TIPS) creation using the Viatorr stent remains relatively uncommon in underdeveloped and high-burden disease regions in... (Comparative Study)
Comparative Study
Transjugular intrahepatic portosystemic shunt (TIPS) creation using the Viatorr stent remains relatively uncommon in underdeveloped and high-burden disease regions in Asia-Pacific, and there is a lack of comparative studies regarding its prognostic effects compared with the generic stent-graft/bare stent combination. The purpose of this retrospective study is to compare the prognostic endpoints of these two treatments in patients who underwent TIPS creation. Clinical data from 145 patients were collected, including 82 in the combination group and 63 in the Viatorr group. Differences in prognostic endpoints (shunt dysfunction, death, overt hepatic encephalopathy [OHE], rebleeding) between the two groups were analyzed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify independent risk factors for post-TIPS shunt dysfunction. The TIPS procedure was successful in all patients. After TIPS creation, both groups showed a significant decrease in porto-caval pressure gradient compared to that before TIPS creation. The stent patency rates at 6, 12, and 18 months were high in both the combination and Viatorr groups (93.7%, 88.5%, and 88.5% vs. 96.7%, 93.4%, and 93.4%, respectively). The stent patency rates was higher in the combination group than in the Viatorr group, although not statistically significant (HR = 2.105, 95% CI 0.640-6.922, Log-rank P = 0.259). There were no significant differences in other prognostic endpoints (death, OHE, rebleeding) between the two groups. The Cox model identified portal vein diameter (HR = 0.807, 95% CI 0.658-0.990, P = 0.040) and portal vein thrombosis (HR = 13.617, 95% CI 1.475-125.678, P = 0.021) as independent risk factors for post-TIPS shunt dysfunction. The shunt patency rates between the Viatorr stent and the generic stent-graft/bare stent combination showed no significant difference and the generic stent-graft/bare stent combination may be a viable alternative in areas where the Viatorr stent is not yet available.
Topics: Humans; Portasystemic Shunt, Transjugular Intrahepatic; Male; Female; Middle Aged; Stents; Retrospective Studies; Aged; Adult; Treatment Outcome; Prognosis; Risk Factors; Hepatic Encephalopathy; Proportional Hazards Models; Kaplan-Meier Estimate
PubMed: 38910214
DOI: 10.1038/s41598-024-64358-0 -
Cellular Signalling Jun 2024In breast cancer, over one third of all patients harbor a somatic mutation in the PIK3CA gene, encoding the p110α catalytic subunit of the phosphatidylinositol 3-kinase...
BACKGROUND
In breast cancer, over one third of all patients harbor a somatic mutation in the PIK3CA gene, encoding the p110α catalytic subunit of the phosphatidylinositol 3-kinase (PI3K) in their tumor cells. Circulating tumor cells (CTCs) are cells shed from the primary tumor into the blood stream. Recently, the long-term stable breast cancer CTC-ITB-01 cell line with tumorigenic and metastatic capacity was established from liquid biopsy derived cells. The oncogenic hotspot PIK3CA mutation H1047R (kinase domain) was detected in the primary tumor, CTCs and metastasis of the same patient. Other PIK3CA mutations located within the C2 domain (E418K and E453K) were detected in the CTCs and the vaginal metastasis but not in the primary tumor. The goal of our study was to functionally characterize the impact of the rare E418K and E453K mutations within the C2 domain that were not detected in the primary tumor.
METHODS
PIK3CA mutations E418K, E453K, H1047R were generated by site-directed mutagenesis and stably overexpressed in breast cancer cells by lentiviral transduction. Subsequent signaling pathway activation was examined by western blot analysis. The impact of PIK3CA mutations on biological processes was studied by live cell imaging using the Incucyte Zoom system. Structural modeling was conducted in Pymol. The membrane localization of the mutants was evaluated by separating the cytosolic and membrane fraction using ultracentrifugation. Drug susceptibility of CTC-ITB-01 cells was analyzed by live cell imaging.
RESULTS
Western blot analysis of human MDA-MB-231, MCF-7 and T47D breast cancer cells stably overexpressing either the PIK3CA wildtype (WT) or one of the E418K, E453K or H1047R mutants revealed a significant increase in AKT phosphorylation in both C2 mutants (E418K and E453K) and the kinase domain mutant H1047R. Functional analysis showed a significantly increased proliferation of MDA-MB-231 cells overexpressing the E453K and H1047R mutants. Migration was increased in all cells overexpressing WT and each of the mutants. Interestingly, invasion and chemotaxis were only enhanced in the MDA-MB-231 cells overexpressing the C2 domain mutants, i.e. E418K and E453K. In addition, membrane localization of the two C2 domain mutants was increased. Structural modeling of the E453K mutation suggests a disruption of the interaction between the negative regulatory domain of the p85α subunit and the p110α catalytic subunit as a potential mechanism leading to the observed activation of PI3K/AKT/mTOR signaling. Dual targeting of AKT/mTOR pathway by MK2206 and RAD001 leads to very strong synergistic effects (IC MK2206: 148 nM, IC RAD001: 15 nM) with respect to proliferation in the CTC-ITB-01 line through apoptosis induction.
CONCLUSIONS
Our results demonstrate that PIK3CA C2 domain mutations activate PI3K downstream AKT signaling and can increase proliferation, migration and invasion after stable lentiviral transduction. Although both investigated mutations - E418K and E453K - are located within the C2 domain, a different molecular mechanism can be proposed. The PIK3CA mutated CTC-ITB-01 shows a high susceptibility against dual inhibition of AKT/mTOR. Further studies are required to fully elucidate the oncogenic potential of rare PIK3CA mutations.
PubMed: 38909932
DOI: 10.1016/j.cellsig.2024.111270 -
Journal of Advanced Research Jun 2024Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications. (Review)
Review
INTRODUCTION
Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications.
OBJECTIVES
This review aims to delve into the complex interactions among immune cells, cytokines, and the inflammatory cascade in atherosclerosis, shedding light on how these elements influence both the initiation and progression of the disease.
METHODS
This review draws on recent clinical research to elucidate the roles of key immune cells, macrophages, T cells, endothelial cells, and clonal hematopoiesis in atherosclerosis development. It focuses on how these cells and process contribute to disease initiation and progression, particularly through inflammation-driven processes that lead to plaque formation and stabilization. Macrophages ingest oxidized low-density lipoprotein (oxLDL), which partially converts to high-density lipoprotein (HDL) or accumulates as lipid droplets, forming foam cells crucial for plaque stability. Additionally, macrophages exhibit diverse phenotypes within plaques, with pro-inflammatory types predominating and others specializing in debris clearance at rupture sites. The involvement of CD4 T and CD8 T cells in these processes promotes inflammatory macrophage states, suppresses vascular smooth muscle cell proliferation, and enhances plaque instability.
RESULTS
The nuanced roles of macrophages, T cells, and the related immune cells within the atherosclerotic microenvironment are explored, revealing insights into the cellular and molecular pathways that fuel inflammation. This review also addresses recent advancements in imaging and biomarker technology that enhance our understanding of disease progression. Moreover, it points out the limitations of current treatment and highlights the potential of emerging anti-inflammatory strategies, including clinical trials for agents such as p38MAPK, tumor necrosis factor α (TNF-α), and IL-1β, their preliminary outcomes, and the promising effects of canakinumab, colchicine, and IL-6R antagonists.
CONCLUSION
This review explores cutting-edge anti-inflammatory interventions, their potential efficacy in preventing and alleviating atherosclerosis, and the role of nanotechnology in delivering drugs more effectively and safely.
PubMed: 38909884
DOI: 10.1016/j.jare.2024.06.016 -
Clinics in Dermatology Jun 2024Artificial Intelligence (AI) has evolved to become a significant force in various domains, including medicine. We explore the role of AI in pathology, with a specific...
Artificial Intelligence (AI) has evolved to become a significant force in various domains, including medicine. We explore the role of AI in pathology, with a specific focus on dermatopathology and neoplastic dermatopathology. AI, encompassing Machine Learning (ML) and Deep Learning (DL), has demonstrated its potential in tasks ranging from diagnostic applications on Whole Slide Imaging (WSI) to predictive and prognostic functions in skin pathology. In dermatopathology, studies have assessed AI's ability to identify skin lesions, classify melanomas, and improve diagnostic accuracy. Results indicate that AI, particularly Convolutional Neural Networks (CNNs), can outperform human pathologists in terms of sensitivity and specificity. Moreover, AI aids in predicting disease outcomes, identifying aggressive tumors, and differentiating between various skin conditions. Neoplastic dermatopathology showcases AI's prowess in classifying melanocytic lesions, discriminating between melanomas and nevi, and aiding dermatopathologists in making accurate diagnoses. Studies emphasize the reproducibility and diagnostic aid that AI provides, especially in challenging cases. In inflammatory and lymphoproliferative dermatopathology, limited research exists, but studies show attempts to use AI to differentiate conditions like Mycosis Fungoides and eczema. While some results are promising, further exploration is needed in these areas. We highlight the extraordinary interest AI has garnered in the scientific community and its potential to assist clinicians and pathologists. Despite the advancements, we have stress edthe importance of collaboration between medical professionals, computer scientists, bioinformaticians, and engineers to harness AI's benefits while acknowledging its limitations and risks. The integration of AI into dermatopathology holds great promise, positioning it as a valuable tool rather than as a replacement for human expertise.
PubMed: 38909860
DOI: 10.1016/j.clindermatol.2024.06.010 -
Journal of Gynecologic Oncology Jun 2024Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA)...
OBJECTIVE
Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients.
METHODS
EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel to identify somatic mutations.
RESULTS
Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2-5 months prior to clinical/radiologic/biomarker progression in 3.
CONCLUSION
ctDNA can reflect larger tumor volume/metastases, treatment response and recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.
PubMed: 38909641
DOI: 10.3802/jgo.2025.36.e5 -
Talanta Jun 2024The certification of cosmetic products has always been a prominent concern. Here, we have developed a pH sensor and applied it in the field of cosmetic safety....
The certification of cosmetic products has always been a prominent concern. Here, we have developed a pH sensor and applied it in the field of cosmetic safety. Initially, we designed two probes, CH with aggregation-induced emission (AIE) effect and the near-infrared fluorophore derivative CYTYR. By encapsulating them with DSPE-PEG2000-NH, we obtained the CHCY-lipo nano-micelles with fluorescence resonance energy transfer (FRET) response. By combining them into a sensor array called pC, we achieved sensitive detection of a wide pH range, ranging from 4.69 to 9.25. To validate the performance of the pC sensor array, we employed a multi-channel mode and applied it to differentiate commercial anti-aging creams. Through linear discriminant analysis and 3D fingerprint analysis, the pC sensor array successfully distinguished anti-aging creams from different countries, providing a rapid and accurate method for cosmetic safety identification. The results of this study demonstrate the potential of the pC sensor array for quick authentication of cosmetic products, offering significant support and application prospects in safeguarding consumer health.
PubMed: 38909596
DOI: 10.1016/j.talanta.2024.126447 -
NeuroImage. Clinical Jun 2024AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated...
INTRODUCTION
AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated by education and occupation, vascular risk factors, and a range of biomarkers associated with both CVD (including white matter hyperintensities [WMH], diffusion MRI abnormalities, infarctions, and microbleeds) and AD (comprising amyloid-PET and tau-PET) collectively influence cognitive function.
METHODS
In this cross-sectional population study, structural equation models were utilized to understand these associations in 449 participants (mean age (SD) = 74.5 (8.4) years; 56% male; 7.5% cognitively impaired).
RESULTS
(1) Higher SES had a protective effect on cognition with mediation through the vascular pathway. (2) The effect of amyloid directly on cognition and through tau was 11-fold larger than the indirect effect of amyloid on cognition through WMH. (3) There is a significant effect of vascular risk on tau deposition.
DISCUSSION
The utilized biomarkers captured the impact of CVD and AD on cognition. The overall effect of vascular risk and SES on these biomarkers are complex and need further investigation.
PubMed: 38909419
DOI: 10.1016/j.nicl.2024.103634