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European Journal of Cardio-thoracic... Sep 2023
PubMed: 37738585
DOI: 10.1093/ejcts/ezad312 -
Frontiers in Oncology 2023Identifying biological markers of colorectal cancer (CRC) development and prognosis and exploring the intrinsic connection between these molecular markers and CRC...
Exploration and validation of the Ki67, Her-2, and mutant P53 protein-based risk model, nomogram and lymph node metastasis model for predicting colorectal cancer progression and prognosis.
INTRODUCTIONS
Identifying biological markers of colorectal cancer (CRC) development and prognosis and exploring the intrinsic connection between these molecular markers and CRC progression is underway. However, a single molecular tumor marker is often difficult to assess and predict the progression and prognosis of CRC. Consequently, a combination of tumor-related markers is much needed. Ki67, Her-2, and mutant P53 (MutP53) proteins play pivotal roles in CRC occurrence, progression and prognosis.
METHODS
Based on the expressions by immunochemistry, we developed a risk model, nomogram and lymph node metastasis model by R software and Pythons to explore the value of these proteins in predicting CRC progression, prognosis, and examined the relationship of these proteins with the CRC clinicopathological features from 755 (training set) and 211 CRC (validation set) patients collected from the hospital.
RESULTS
We found that Ki67 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular invasion, organization differentiation, and adenoma carcinogenesis. Moreover, Her-2 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, pMMR/dMMR, signet ring cell carcinoma, and organization differentiation. MutP53 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, adenoma carcinogenesis, signet ring cell carcinoma, organization differentiation, and pMMR/dMMR. Increased expression of each of the protein indicated a poor prognosis. The established risk model based on the three key proteins showed high predictive value for determining the pathological characteristics and prognosis of CRC and was an independent influencer for prognosis. The nomogram prediction model, which was based on the risk model, after sufficient evaluation, showed more premium clinical value for predicting prognosis. Independent cohort of 211 CRC patients screened from the hospital verified the strong predictive efficacy of these models. The utilization of the XGBoost algorithm in a lymph node metastasis model, which incorporates three crucial proteins, demonstrated a robust predictive capacity for lymph node metastasis.
DISCUSSION
The risk model, nomogram and lymph node metastasis model have all provided valuable insights into the involvement of these three key proteins in the progression and prognosis of CRC. Our study provides a theoretical basis for further screening of effective models that utilize biological markers of CRC.
PubMed: 38074671
DOI: 10.3389/fonc.2023.1236441 -
Fluid-structure interactions of peripheral arteries using a coupled in silico and in vitro approach.Computers in Biology and Medicine Oct 2023Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts....
Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction results as a numerical model and physical prototype. This numerical one-way and two-way fluid-structure interaction study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms via direct pressurisation and ring tensile testing. Phantoms within a compliance range of 1.4-68.0%/100 mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with moderately statistically significant differences in measured compliance ranging between 10 and 20% for the two methods. One-way fluid-structure interaction coupling underestimated arterial wall compliance by up to 14.7% compared with two-way coupled models. Overall, Solaris™ (Smooth-On) matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.
Topics: Humans; Models, Cardiovascular; Femoral Artery; Computer Simulation; Silicones; Stress, Mechanical
PubMed: 37703711
DOI: 10.1016/j.compbiomed.2023.107474 -
Diabetology & Metabolic Syndrome Dec 2023Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes...
BACKGROUND
Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke.
METHODS
Patients with ischemic stroke without a history of diabetes mellitus in the Third China National Stroke Registry were included. Adipose tissue specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 5 groups according to the quintiles. Outcomes included stroke recurrence (ischemic or hemorrhagic), combined vascular events, all-cause death, and poor outcome (modified Rankin Scale, 3-6) at 12 months after stroke onset. We assessed the association between Adipo-IR and risk of prognosis by multivariable Cox/logistic regression models adjusted for potential covariates.
RESULTS
Among 2,222 patients, 69.0% were men with a mean age of 62.5 years. At 12 months, 185 (8.3%) patients had recurrent stroke, 193 (8.7%) had combined vascular events, 58 (2.6%) died, and 250 (11.5%) had a poor outcome. Compared with patients with the lowest quintile, patients with the second, third, fourth, fifth quintiles of the Adipo-IR were associated with an increased risk of stroke recurrence (hazard ratio [HR], 1.77; 95% CI, 1.04-3.03; P = 0.04; HR, 2.19; 95% CI, 1.30-3.68; P = 0.003; HR, 1.84; 95% CI, 1.06-3.21; P = 0.03; HR, 2.11; 95% CI, 1.20-3.71; P = 0.01, respectively) and marginally associated with an increased risk of combined vascular events ( HR, 1.60; 95%CI, 0.97-2.64; P = 0.07; HR, 1.91; 95% CI, 1.17-3.13; P = 0.01; HR, 1.62; 95% CI, 0.96-2.75; P = 0.07; HR, 1.80; 95% CI, 1.05-3.09; P = 0.03, respectively) at 12 months after adjustment for potential covariates. Adipo-IR was not associated with mortality and poor outcome at 12 months.
CONCLUSIONS
These findings suggest that adipose tissue specific insulin resistance is independently associated with recurrent stroke and combined vascular events after acute ischemic stroke in nondiabetic patients.
PubMed: 38041145
DOI: 10.1186/s13098-023-01235-2 -
Archiv Der Pharmazie Apr 2024Cancer has become a major concern in healthcare globally, and over time, incidences and prevalence of cancer are increasing. To counter this, a lot of anticancer drugs... (Review)
Review
Cancer has become a major concern in healthcare globally, and over time, incidences and prevalence of cancer are increasing. To counter this, a lot of anticancer drugs are approved and are in clinical use, playing a pivotal role in its treatment. Due to drug resistance and adverse effects, a continuous demand for novel, potent, and safe candidates to treat cancer is always there. Over the last few decades, various heterocyclic ring-based derivatives have been explored and reported in the literature. In this regard, benzothiazole scaffold-based compound emerged as the versatile ring for developing novel and safe anticancer candidates. In this article, we have reported various benzothiazole heterocyclic ring-based derivatives demonstrating potent antiproliferative activity by induction of apoptosis via an intrinsic pathway in a dose-dependent manner. These compounds also displayed inhibition of different enzymes, for example, Aurora kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, phosphoinositide kinases, DNA topoisomerase, and tubulin polymerases. This study focused on a comprehensive overview of antiproliferative activity, structure-activity relationship, apoptosis induction activity, and enzyme inhibition by benzothiazole-based compounds.
Topics: Humans; Structure-Activity Relationship; Vascular Endothelial Growth Factor A; Cell Proliferation; Benzothiazoles; Neoplasms; Antineoplastic Agents; Apoptosis; Drug Screening Assays, Antitumor; Molecular Structure
PubMed: 38212254
DOI: 10.1002/ardp.202300493 -
JACC. Cardiovascular Imaging Apr 2024Although patients with high-risk plaque (HRP) on coronary computed tomography angiography (CTA) are reportedly at increased risk for future cardiovascular events,...
BACKGROUND
Although patients with high-risk plaque (HRP) on coronary computed tomography angiography (CTA) are reportedly at increased risk for future cardiovascular events, individual HRP features have not been systematically validated against high-resolution intravascular imaging.
OBJECTIVES
The aim of this study was to correlate HRP features on CTA with plaque characteristics on optical coherence tomography (OCT).
METHODS
Patients who underwent both CTA and OCT before coronary intervention were enrolled. Plaques in culprit vessels identified by CTA were evaluated with the use of OCT at the corresponding sites. HRP was defined as a plaque with at least 2 of the following 4 features: positive remodeling (PR), low-attenuation plaque (LAP), napkin-ring sign (NRS), and spotty calcification (SC). Patients were followed for up to 3 years.
RESULTS
The study included 448 patients, with a median age of 67 years and of whom 357 (79.7%) were male, and 203 (45.3%) presented with acute coronary syndromes. A total of 1,075 lesions were analyzed. All 4 HRP features were associated with thin-cap fibroatheroma. PR was associated with all OCT features of plaque vulnerability, LAP was associated with lipid-rich plaque, macrophage, and cholesterol crystals, NRS was associated with cholesterol crystals, and SC was associated with microvessels. The cumulative incidence of the composite endpoint (target vessel nontarget lesion revascularization and cardiac death) was significantly higher in patients with HRP than in those without HRP (4.7% vs 0.5%; P = 0.010).
CONCLUSIONS
All 4 HRP features on CTA were associated with features of vulnerability on OCT. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).
Topics: Humans; Male; Aged; Female; Plaque, Atherosclerotic; Computed Tomography Angiography; Coronary Artery Disease; Coronary Angiography; Tomography, Optical Coherence; Coronary Vessels; Predictive Value of Tests; Cholesterol
PubMed: 37715773
DOI: 10.1016/j.jcmg.2023.08.005 -
Plant Signaling & Behavior Dec 2023Plants require sunlight, carbon dioxide, water and mineral ions for their growth and development. Roots in vascular plants sequester water and ions from soil and...
Plants require sunlight, carbon dioxide, water and mineral ions for their growth and development. Roots in vascular plants sequester water and ions from soil and transport them to the aboveground parts of the plant. Due to heterogeneous nature of soil, roots have evolved several regulatory barriers from molecular to organismic level that selectively allows certain ions to enter the vascular tissues for transport according to the physiological and metabolic demands of plant cell. Current literature profusely elaborates about apoplastic barriers, but the possibility of the existence of a symplastic regulation through phosphorous-enriched cells has not been mentioned. Recent investigations on native ion distribution in seedling roots of several species ( and ) identified an ionomic structure termed as "P-ring". The P-ring is composed of a group of phosphorous-rich cells arranged in radial symmetry encircling the vascular tissues. Physiological investigations indicate that the structure is relatively inert to external temperature and ion fluctuations while anatomical studies indicates that they are less likely to be apoplastic in nature. Furthermore, their localization surrounding vascular tissues and in evolutionarily distinct plant lineages might indicate their conserved nature and involvement in ion regulation. Undoubtedly, this is an interesting and important observation that has significant merit for further investigations by the plant science community.
Topics: Seedlings; Phosphorus; Biological Transport; Plant Roots; Water; Soil
PubMed: 37332191
DOI: 10.1080/15592324.2023.2217389 -
Journal of Cardiovascular Translational... Oct 2023An increasing body of research indicates that annular stability plays a key role for a successful aortic valve repair. The aim of this study was to evaluate and compare...
An increasing body of research indicates that annular stability plays a key role for a successful aortic valve repair. The aim of this study was to evaluate and compare a novel open aortic annuloplasty ring (the A-ring) with the Dacron ring. Both rings were compared with native aortic roots in vitro. Eighteen aortic roots were included in the study and randomized into three groups: the native, Dacron, and A-ring group. The roots were evaluated in an in vitro physiologic pulsatile model simulating the left side of the heart. Aortic annulus diameters were significantly reduced both in the Dacron ring group (p = 0.003) and the A-ring group (p = 0.020) when compared with the native group. Both the Dacron ring and A-ring effectively downsized the aortic annulus diameter. The A-ring also displayed an ability to maintain aortic root distensibility during the cardiac cycle equally to the Dacron ring.
Topics: Humans; Aortic Valve; Aortic Valve Insufficiency; Polyethylene Terephthalates; Prosthesis Design; Cardiac Valve Annuloplasty; Heart Valve Prosthesis
PubMed: 37261643
DOI: 10.1007/s12265-023-10393-7 -
Cell Communication and Signaling : CCS Oct 2023Familial hyperkalemic hypertension (FHHt), also known as Pseudohypoaldosteronism type II (PHAII) or Gordon syndrome is a rare Mendelian disease classically characterized... (Review)
Review
Familial hyperkalemic hypertension (FHHt), also known as Pseudohypoaldosteronism type II (PHAII) or Gordon syndrome is a rare Mendelian disease classically characterized by hyperkalemia, hyperchloremic metabolic acidosis, and high systolic blood pressure. The most severe form of the disease is caused by autosomal dominant variants in CUL3 (Cullin 3), a critical subunit of the multimeric CUL3-RING ubiquitin ligase complex. The recent identification of a novel FHHt disease variant of CUL3 revealed intricacies within the underlying disease mechanism. When combined with studies on canonical CUL3 variant-induced FHHt, these findings further support CUL3's role in regulating renal electrolyte transport and maintaining systemic vascular tone. However, the pathophysiological effects of CUL3 variants are often accompanied by diverse systemic disturbances in addition to classical FHHt symptoms. Recent global proteomic analyses provide a rationale for these systemic disturbances, paving the way for future mechanistic studies to reveal how CUL3 variants dysregulate processes outside of the renovascular axis. Video Abstract.
Topics: Humans; Pseudohypoaldosteronism; Proteomics; Kidney; Hypertension; Cullin Proteins
PubMed: 37845702
DOI: 10.1186/s12964-023-01269-z -
Proceedings of the National Academy of... Apr 2024The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These...
The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, we identified that decorin down-regulated a cluster of tumor-associated genes involved in lymphatic vessel (LV) development when systemically delivered to mice harboring breast carcinoma allografts. We found that Lyve1 and Podoplanin, two established markers of LVs, were markedly suppressed at both the mRNA and protein levels, and this suppression correlated with a significant reduction in tumor LVs. We further identified that soluble decorin, but not its homologous proteoglycan biglycan, inhibited LV sprouting in an ex vivo 3D model of lymphangiogenesis. Mechanistically, we found that decorin interacted with vascular endothelial growth factor receptor 3 (VEGFR3), the main lymphatic RTK, and its activity was required for the decorin-mediated block of lymphangiogenesis. Finally, we identified that Lyve1 was in part degraded via decorin-evoked autophagy in a nutrient- and energy-independent manner. These findings implicate decorin as a biological factor with antilymphangiogenic activity and provide a potential therapeutic agent for curtailing breast cancer growth and metastasis.
Topics: Decorin; Lymphangiogenesis; Animals; Mice; Humans; Female; Breast Neoplasms; Lymphatic Vessels; Cell Line, Tumor; Disease Progression; Vesicular Transport Proteins; Membrane Glycoproteins; Gene Expression Regulation, Neoplastic
PubMed: 38652741
DOI: 10.1073/pnas.2317760121