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Molecular Medicine (Cambridge, Mass.) May 2024Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular...
BACKGROUND
Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism.
METHODS
Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus.
RESULTS
Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion.
CONCLUSION
These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.
Topics: Female; Humans; Glutaminase; RNA, Long Noncoding; Endometriosis; RNA Stability; Glutamine; RNA-Binding Proteins; Cell Proliferation; Adult; RNA, Messenger; Gene Expression Regulation; Protein Binding
PubMed: 38760723
DOI: 10.1186/s10020-024-00834-7 -
Frontiers in Veterinary Science 2024Digital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the...
INTRODUCTION
Digital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the diagnostic yield of DT in identifying predefined anatomic structures in feline cadaver heads, comparing it with conventional intraoral dental radiography (DR).
METHODS
A total of 16 feline cadaver heads were utilized to evaluate 19 predefined clinically relevant anatomic structures using both DR and DT. A semi-quantitative scoring system was employed to characterize the ability of each imaging method to identify these structures.
RESULTS
DT demonstrated a significantly higher diagnostic yield compared to DR for all evaluated anatomic structures. Orthogonal DT imaging identified 13 additional anatomic landmarks compared to a standard 10-view feline set obtained via DR. Moreover, DT achieved statistically significant higher scores for each of these landmarks, indicating improved visualization over DR.
DISCUSSION
These findings validate the utility of DT technology in reliably identifying clinically relevant anatomic structures in the cat skull. This validation serves as a foundation for further exploration of DT imaging in detecting dentoalveolar and other maxillofacial bony lesions and pathologies in cats.
PubMed: 38756522
DOI: 10.3389/fvets.2024.1408807 -
Cureus Apr 2024Aims Spondylodiscitis (SpD), a debilitating infective condition of the spine, mandates early diagnosis and institution of appropriate therapy, for which accurate...
Aims Spondylodiscitis (SpD), a debilitating infective condition of the spine, mandates early diagnosis and institution of appropriate therapy, for which accurate microbiology and histological evaluation of the affected tissue is vital. The objectives of the study were to assess the correlation between clinical and magnetic resonance imaging (MRI) findings with histopathology (HPE) and microbiology (MB) in clinically diagnosed spondylodiscitis. Settings and design This was a prospective study of 34 consecutive patients reporting at the outpatient department of a tertiary hospital with clinical and imaging features of SpD, who underwent image-guided/surgical biopsy of lesions. Methods and material The provisional diagnosis of SpD in all patients was made on the combined basis of clinical profile and MRI Spine findings. Tissue samples in all patients, obtained by either open surgery or CT-guided biopsy, were subjected to HPE and MB analysis. Results SpD has a bimodal age distribution with the majority of patients being males in the fourth to fifth decades. Only raised erythrocyte sedimentation rate (ESR) was consistently seen amongst laboratory parameters, with leucocytosis being added pointer towards pyogenic etiology. MRI remained the imaging modality of choice for SpD but was not dependable for etiologic differentiation. On HPE and MB evaluations, 24 patients (71%) had findings consistent with infective SpD, while combined results augmented etiologic confirmation for 28 patients (82.4%). HPE was more sensitive than traditional MB methods to determine etiology in SpD, but the addition of the GeneXpert (Cepheid, Sunnyvale, California, United States) technique improved the MB positivity rate, especially in patients with tubercular SpD. Six patients (17.6%) with both negative HPE and MB results were categorized as 'Non-specific' SpD. Conclusions SpD poses a challenge to determine the etiology for the administration of specific antimicrobial therapy. A stratified standard institutional approach needs adoption to systematically evaluate SpD patients by having a high index of clinical suspicion, early imaging, followed by tissue biopsy for HPE and MB. Despite efforts to reach a diagnosis, a subset of patients without conclusive etiologic agent identification would remain as 'Non-specific', needing empiric antibiotic treatment based on clinico-radiologic profile.
PubMed: 38752024
DOI: 10.7759/cureus.58284 -
Frontiers in Oncology 2024Early detection of cancer is crucial to reducing fatalities and improving patient outcomes. Metastasis is the first stage of aggressive cancers, often occurring before... (Review)
Review
Early detection of cancer is crucial to reducing fatalities and improving patient outcomes. Metastasis is the first stage of aggressive cancers, often occurring before primary lesions can be seen. It occurs when cancerous cells disseminate to distant, non-malignant organs through the bloodstream, known as circulating tumor cells (CTCs). CTCs, or cancer tumor cells, are valuable indicators for predicting treatment response, metastasis progression, and disease progression. However, they are primarily used for research due to challenges like heterogeneity, separation from blood, and lack of clinical validation. Only a few methods have been approved for clinical use. One area of research is the isolation and identification of CTCs, which could significantly impact early cancer detection and prognosis. Current technologies using whole-blood samples use size, immunoaffinity, and density approaches, along with positive and negative enrichment techniques. Surface modification of nanomaterials is important for effective cancer therapies because it improves their ability to target and reduces interactions with healthy tissues. Consequently, researchers have created biomimetic nanoparticles covered with cell membranes using functional, targeted, and biocompatible coating technology. Nanoparticles with membranes can target specific cells, stay in circulation for longer, and avoid immune responses, which makes them much better at capturing CTCs. This study examines the current opportunities and difficulties associated with using cell membrane-coated nanoparticles as a capture technique for CTCs. In addition, we examine potential future developments in light of the current obstacles and investigate areas that require further research to fully understand its growing clinical possibilities.
PubMed: 38746681
DOI: 10.3389/fonc.2024.1389775 -
Journal of Biomedical Optics Jun 2024Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is... (Observational Study)
Observational Study
SIGNIFICANCE
Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is non-specific, frequently leading to misdiagnosis and delays in care. No current strategies yield an accurate, real-time diagnosis of an NSTI.
AIM
A first-in-kind, observational, clinical pilot study tested the hypothesis that measurable fluorescence signal voids occur in NSTI-affected tissues following intravenous administration and imaging of perfusion-based indocyanine green (ICG) fluorescence. This hypothesis is based on the established knowledge that NSTI is associated with local microvascular thrombosis.
APPROACH
Adult patients presenting to the Emergency Department of a tertiary care medical center at high risk for NSTI were prospectively enrolled and imaged with a commercial fluorescence imager. Single-frame fluorescence snapshot and first-pass perfusion kinetic parameters-ingress slope (IS), time-to-peak (TTP) intensity, and maximum fluorescence intensity (IMAX)-were quantified using a dynamic contrast-enhanced fluorescence imaging technique. Clinical variables (comorbidities, blood laboratory values), fluorescence parameters, and fluorescence signal-to-background ratios (SBRs) were compared to final infection diagnosis.
RESULTS
Fourteen patients were enrolled and imaged (six NSTI, six cellulitis, one diabetes mellitus-associated gangrene, and one osteomyelitis). Clinical variables demonstrated no statistically significant differences between NSTI and non-NSTI patient groups (). All NSTI cases exhibited prominent fluorescence signal voids in affected tissues, including tissue features not visible to the naked eye. All cellulitis cases exhibited a hyperemic response with increased fluorescence and no distinct signal voids. Median lesion-to-background tissue SBRs based on snapshot, IS, TTP, and IMAX parameter maps ranged from 3.2 to 9.1, 2.2 to 33.8, 1.0 to 7.5, and 1.5 to 12.7, respectively, for the NSTI patient group. All fluorescence parameters except TTP demonstrated statistically significant differences between NSTI and cellulitis patient groups ().
CONCLUSIONS
Real-time, accurate discrimination of NSTIs compared with non-necrotizing infections may be possible with perfusion-based ICG fluorescence imaging.
Topics: Humans; Indocyanine Green; Female; Male; Soft Tissue Infections; Middle Aged; Optical Imaging; Pilot Projects; Aged; Prospective Studies; Adult; Necrosis
PubMed: 38745983
DOI: 10.1117/1.JBO.29.6.066003 -
Alternative Therapies in Health and... May 2024Breast cancer is a prevalent malignancy globally, necessitating accurate diagnostic tools for early detection and intervention. Ultrasound imaging plays an important...
BACKGROUND
Breast cancer is a prevalent malignancy globally, necessitating accurate diagnostic tools for early detection and intervention. Ultrasound imaging plays an important role in breast lesion assessment, with various morphological features serving as key indicators of malignancy.
OBJECTIVE
This study aimed to employ logistic regression analysis to investigate ultrasound indices for effectively distinguishing between benign and malignant breast masses.
METHODS
A careful retrospective analysis was conducted on a dataset comprising 388 pathologically confirmed breast masses retrieved from 364 female patients, of which 142 were identified as malignant and 246 as benign. The primary outcome measures included the aspect ratio of breast masses, clarity of mass boundaries, and presence of spiculations and angularity, which were assessed through ultrasound imaging and analyzed using multifactorial logistic regression.
RESULTS
The analysis demonstrated that the aspect ratio, clarity of boundaries, and presence of spiculations and angularity were significant independent risk factors for identifying malignant breast masses (P < .001). Multifactorial logistic regression revealed age (OR=1.183, 95% CI 1.119-1.252, P < .001), mass size (OR=1.087, 95% CI 1.036-1.140, P = .001), marginal spiculation (OR=8.296, 95% CI 2.325-29.598, P = .001), defined borders (OR=5.500, 95% CI 1.765-14.140, P = .003), aspect ratio (OR=5.830, 95% CI 1.742-19.505, P = .004), margin angularity (OR=5.183, 95% CI 1.910-14.063, P = .001), and marginal microtubules (OR=9.180, 95% CI 2.307-36.523, P = .002) significantly influenced mass benignity.
CONCLUSIONS
The aspect ratio, boundary clarity, and presence of spiculation and angularity serve as crucial predictive indicators for distinguishing between benign and malignant breast lumps. Moreover, the utilization of a multifactorial logistic regression model significantly enhances the identification and differentiation of the benign and malignant nature of breast lumps. Continued research in this area is essential for further refining diagnostic approaches and enhancing overall breast cancer management.
PubMed: 38743902
DOI: No ID Found -
Journal of Investigative Medicine High... 2024Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is... (Review)
Review
Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.
Topics: Humans; Male; Biopsy; Diagnosis, Differential; Fatal Outcome; Lymphohistiocytosis, Hemophagocytic; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Panniculitis; Skin; Skin Neoplasms; Young Adult
PubMed: 38742532
DOI: 10.1177/23247096241253337 -
Surgical Case Reports May 2024Malignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant...
BACKGROUND
Malignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant perineuriomas; however, patients often develop recurrence after resection, and effective treatment for advanced or recurrent lesions needs to be established. This report describes a 51-year-old female with a rare malignant perineurioma in the retroperitoneum, which contributing valuable insights to the literature.
CASE PRESENTATION
The patient presented with abdominal distension and the imaging work-up revealed a huge hemorrhagic tumor in the retroperitoneum and obstruction of inferior vena cava by the tumor. The patient underwent surgery retrieving the tumor combined with left hemiliver and retrohepatic vena cava, which confirmed the diagnosis of a malignant perineurioma based on histopathological and immunohistochemical examination. Cancer gene panel testing identified mutations in NF2. Radiotherapy was administered for peritoneal dissemination 2 months after surgery, and the patient died from disease progression 6 months after surgery.
CONCLUSIONS
This rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.
PubMed: 38739347
DOI: 10.1186/s40792-024-01915-9 -
Cureus Apr 2024With rising cases of renal cell carcinoma (RCC), precise identification of tumor subtypes is essential, particularly for detecting small, heterogenous lesions often...
INTRODUCTION
With rising cases of renal cell carcinoma (RCC), precise identification of tumor subtypes is essential, particularly for detecting small, heterogenous lesions often overlooked in traditional histopathological examinations. This study demonstrates the non-invasive use of deep learning for Histopathological differentiation of renal tumors through quadriphasic multidetector computed tomography (MDCT).
PATIENTS AND METHODS
This prospective longitudinal study includes 50 subjects (32 males, 18 females) with suspected renal tumors. A deep neural network (DNN) is developed to predict RCC subtypes using peak attenuation values measured in Hounsfield Units (HUs) obtained from quadriphasic MDCT scans. The network then generates confidence scores for each of the four primary subtypes of renal tumors, effectively distinguishing between benign oncocytoma and various malignant subtypes.
RESULTS
Our neural network accurately distinguishes Renal tumor subtypes, including clear cell, papillary, chromophobe, and benign oncocytoma, with a confidence score of 68% with the network's diagnosis aligning with Histopathological examinations. Our network was also able to accurately classify RCC subtypes on a synthetically generated dataset with 20,000 samples.
CONCLUSION
We developed an artificial intelligence-based RCC subtype classification technique. Our approach is non-invasive and has the potential to transform the methodology in Renal oncology by providing accurate and timely diagnostic information and enhancing clinical decisions.
PubMed: 38738077
DOI: 10.7759/cureus.57959 -
Journal of Medicine and Life Jan 2024Colorectal cancer (CRC) is one of the most frequent types of cancer, with high incidence rates and mortality globally. The extended timeframe for developing CRC allows... (Review)
Review
Colorectal cancer (CRC) is one of the most frequent types of cancer, with high incidence rates and mortality globally. The extended timeframe for developing CRC allows for the potential screening and early identification of the disease. Furthermore, studies have shown that survival rates for patients with cancer are increased when diagnoses are made at earlier stages. Recent research suggests that the development of CRC, including its precancerous lesion, is influenced not only by genetic factors but also by epigenetic variables. Studies suggest epigenetics plays a significant role in cancer development, particularly CRC. While this approach is still in its early stages and faces challenges due to the variability of CRC, it shows promise as a potential method for understanding and addressing the disease. This review examined the current evidence supporting genetic and epigenetic biomarkers for screening and diagnosis. In addition, we also discussed the feasibility of translating these methodologies into clinical settings. Several markers show promising potential, including the methylation of vimentin (), syndecan-2 (), and septin 9 (). However, their application as screening and diagnostic tools, particularly for early-stage CRC, has not been fully optimized, and their effectiveness needs validation in large, multi-center patient populations. Extensive trials and further investigation are required to translate genetic and epigenetic biomarkers into practical clinical use. biomarkers, diagnostic biomarkers.
Topics: Humans; Colorectal Neoplasms; Biomarkers, Tumor; Epigenesis, Genetic; Early Detection of Cancer; Septins; DNA Methylation; Syndecan-2; Vimentin
PubMed: 38737656
DOI: 10.25122/jml-2023-0269