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Biomedicine & Pharmacotherapy =... Dec 2023Twenty-seven compounds bearing a tetrazole ring as a central unit have been designed, synthetized and biologically evaluated. Studies have been performed in order to...
Twenty-seven compounds bearing a tetrazole ring as a central unit have been designed, synthetized and biologically evaluated. Studies have been performed in order to compare the effect of tetrazole derivatives bearing amine electron-donor or nitro electron-acceptor groups. The antiproliferative activity has been determined in monoculture studies on tumor cell lines HT-29, A-549, MCF-7 and on non-tumor cell line HEK-293 as well as in co-culture studies (HT-29/THP-1). All the compounds have been studied as PD-L1 (Programmed Death Ligand 1), VEGFR-2 (Vascular Endothelial Growth Factor 2), CD-47 (Cluster of Differentiation 47) and c-Myc inhibitors. The effect on TNF-α secretion has also been determined. Bromoderivatives 23, 24 and chloroderivatives 26, 27 have demonstrated an apoptotic effect on HT-29 cancer cells. Compounds bearing an amine group have shown very promising effects as TME immunomodulatory agents.
Topics: Humans; Antineoplastic Agents; Immunomodulating Agents; Vascular Endothelial Growth Factor A; Tumor Microenvironment; HEK293 Cells; Cell Line, Tumor; Tetrazoles; Amines; Vascular Endothelial Growth Factor Receptor-2; Cell Proliferation; Structure-Activity Relationship; Drug Screening Assays, Antitumor
PubMed: 37976894
DOI: 10.1016/j.biopha.2023.115668 -
Journal of Endovascular Therapy : An... Nov 2023The performance of fenestrated endovascular aortic aneurysm repair (FEVAR) may be compromised by complications related to the dynamic vascular environment. The aim of...
Renal and Visceral Artery Configuration During the First Year of Follow-Up After Fenestrated Aortic Aneurysm Repair Using the Anaconda Stent-graft: A Prospective Longitudinal Multicenter Study With ECG-Gated CTA Scans.
OBJECTIVE
The performance of fenestrated endovascular aortic aneurysm repair (FEVAR) may be compromised by complications related to the dynamic vascular environment. The aim of this study was to analyze the behavior of FEVAR bridging stent configurations during the cardiac cycle and during follow-up to improve our understanding on treatment durability.
DESIGN
Twenty-one patients presenting with complex abdominal aortic aneurysms (AAAs; 9 juxtarenal/6 pararenal/3 paravisceral/1 thoracoabdominal aortic aneurysm type IV), treated with a fenestrated Anaconda (Terumo Aortic, Inchinnan, Scotland, UK) with Advanta V12 bridging stents (Getinge, Merrimack, NH, USA), were prospectively enrolled in a multicenter observational cohort study and underwent electrocardiogram (ECG)-gated computed tomographic angiography (CTA) preoperatively, at discharge, 7-week, and 12-month follow-ups.
METHODS
Fenestrated endovascular aortic aneurysm repair stability was assessed considering the following variables: branch angle as the angle between the aorta and the target artery, end-stent angle as the angle between the end of the bridging stent and the native artery downstream from it, curvature and tortuosity index (TI) to describe the bending of the target artery. Body-bridging stent stability was assessed considering bridging stent flare lengths, the distances between the proximal sealing stent-ring and fenestrations and the distance between the fenestration and first apposition in the target artery.
RESULTS
Renal branch angles significantly increased after FEVAR toward a perpendicular position (right renal artery from median 60.9°, inter quartile range [IQR]=44.2-84.9° preoperatively to 94.4°, IQR=72.6-99.8°, p=0.001 at 12-month follow-up; left renal artery [LRA], from 63.7°, IQR=55.0-73.0° to 94.3°, IQR=68.2-105.6°, p<0.001), while visceral branch angles did not. The mean dynamic curvature only decreased for the LRA from preoperative (3.0, IQR=2.2-3.8 m) to 12-month follow-up (1.9, IQR=1.4-2.6 m, p=0.027). The remaining investigated variables did not seem to show any changes over time in this cohort.
CONCLUSIONS
Fenestrated endovascular aortic aneurysm repair for complex AAAs using the Anaconda fenestrated stent-graft and balloon-expandable Advanta V12 bridging stents demonstrated stable configurations up to 12-month follow-up, except for increasing renal branch angles toward perpendicular orientation to the aorta, yet without apparent clinical consequences in this cohort.
CLINICAL IMPACT
This study provides detailed information on the cardiac-pulsatility-induced (dynamic) and longitudinal geometry deformations of the target arteries and bridging stents after fenestrated endovascular aortic aneurysm repair (FEVAR) up to 12-month follow-up. The configuration demonstrated limited dynamic and longitudinal deformations in terms of branch angle, end-stent angle, curvature, and tortuosity index (TI), except for the increasing renal branch angles that go toward a perpendicular orientation to the aorta. Overall, the results suggest that the investigated FEVAR configurations are stable and durable, though careful consideration of increasing renal branch angles and significant geometry alterations is advised.
PubMed: 37933525
DOI: 10.1177/15266028231209929 -
JVS-vascular Science 2023Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation...
OBJECTIVE
Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation (endothelial dysfunction) are key metrics of impaired arterial health in peripheral arterial disease (PAD). To allow for comparative testing of arteries during standard laboratory hours, storage buffers and conditions have been used to extend the functional life of arteries. Various storage conditions have been compared, but there has not been a robust comparison or validation in human arteries. The objective of this work is to optimize storage of arterial segments for endothelial cell (EC) testing in a murine model and to test EC function in human PAD arteries. We hypothesized that certain storage conditions would be superior to others.
METHODS
Healthy murine aortas were harvested from 10- to 14-week-old C57/Bl6J male and female mice and compared under different storage protocols (24 hours) to immediate arterial testing. The storage conditions tested were: Opti-MEM (37°C or 4°C), Krebs-HEPES with 1.8 mmol/L or 2.5 mmol/L calcium (4°C), or Wisconsin (WI) solution at 4°C. Vascular function was evaluated by isometric force testing. Endothelium-dependent and -independent relaxation were measured after precontraction with addition of methacholine or sodium nitroprusside, respectively. Arterial contraction was stimulated with potassium chloride or phenylephrine. Analysis of variance was used to determine significance compared with immediate testing with < .05. Under institutional review board approval, 28 PAD arteries were collected at amputation and underwent vascular function testing as described. Disturbed flow conditions were determined by indirect (upstream occlusion) flow to the harvested tibial arteries. Stable flow arteries had in-line flow. Arterial calcification was quantified manually as present or not present.
RESULTS
We found that 4°C WI and 37°C Opti-MEM best preserved endothelium-dependent relaxation and performed similarly to immediately testing aortas (termed fresh for freshly tested) ( > .95). Other storage conditions were inferior to freshly tested aortas ( < .05). Vascular smooth muscle function was tested by endothelial-independent relaxation and contractility. All storage conditions preserved endothelial-independent relaxation and contractility similar to freshly tested arteries. However, 4°C WI and 37°C Opti-MEM storage conditions most closely approximated the maximum force of contraction of freshly tested arteries in response to potassium chloride ( > .39). For human arterial testing, 28 tibial arteries were tested for relaxation and contraction with 16 arteries with peripheral artery occlusive disease (PAD with disturbed flow) and 12 without peripheral artery occlusive disease (PAD with stable flow), of which 14 were calcified and 14 were noncalcified. Endothelial-dependent relaxation data was measurable in 9 arteries and arterial contraction data was measurable in 14 arteries. When comparing flow conditions, arteries exposed to disturbed flow (n = 4) had significantly less relaxation (2% vs 59%; = .03) compared with stable flow conditions (n = 5). In contrast, presence the (n = 6) or absence of calcification (n = 3) did not impact arterial relaxation. Arterial contraction was not different between groups in either comparison by flow (n = 9 disturbed; n = 5 stable) or calcification (n = 6 present; n = 8 absent).
CONCLUSIONS
In healthy murine aortas, arterial storage for 24 hours in 4°C WI or 37°C Opti-MEM both preserved endothelium-dependent relaxation and maximum force of contraction. In human PAD arteries stored in 4° WI, flow conditions before arterial harvest, but not arterial calcification, led to differences in arterial relaxation in human PAD arteries. Arterial contractility was more robust (11/28 arteries) compared with arterial relaxation (7/28 arteries), but was not significantly different under flow or calcification parameters. This work defines ideal storage conditions for arterial ring testing and identifies that EC dysfunction from disturbed flow may persist in delayed ex vivo arterial testing.
PubMed: 37649473
DOI: 10.1016/j.jvssci.2023.100122 -
Cureus Oct 2023Tracheal stenosis can occur from several malignant and non-malignant conditions, including vascular ring/aneurysms, tracheomalacia, bronchomalacia, endotracheal tubes...
Tracheal stenosis can occur from several malignant and non-malignant conditions, including vascular ring/aneurysms, tracheomalacia, bronchomalacia, endotracheal tubes (ETT), tracheostomy tubes, mucus plug, burn, trauma, tuberculosis, etc. Significant tracheal stenosis typically requires management by bronchoscopy, dilatation, or surgical resection. Bronchoscopic balloon dilatation is a simple, inexpensive, safe, and minimally invasive method that can be used to dilate airway stenosis and restore adequate airflow. A Montgomery tracheostomy tube is often used as a combined tracheal stent and airway device. We describe a 68-year-old female with tracheal stenosis, which was managed with an unconventional approach, a non-compliant endovascular balloon, due to resource scarcity.
PubMed: 38021857
DOI: 10.7759/cureus.47496 -
BMC Ophthalmology Feb 2024To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic...
BACKGROUND
To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic choroidal neovascularization (ICNV).
METHODS
This retrospective study analyzed outcomes in 40 patients (40 eyes) with ICNV who received intravitreal injections of conbercept 0.5 mg (0.05 ml) and were followed up for at least 12 months. All patients underwent full ophthalmic examinations, including best-corrected vision acuity (BCVA), intraocular pressure (IOP), slit-lamp examination, color fundus photography, optical coherence tomography angiography, multifocal electroretinogram, and fundus fluorescence angiography, if necessary, at baseline and after 1, 3, 6, and 12 months. BCVA, macular central retinal thickness (CRT), IOP, CNV blood flow area, thickness of the CNV-pigment epithelial detachment complex, thickness of the retinal nerve fiber layer (RNFL), and the first positive peak (P1) amplitude density in ring 1 before and after treatment were compared.
RESULTS
Mean baseline BCVA (logMAR), CRT, CNV blood flow area, and CNV-pigment epithelial detachment complex thickness were significantly lower 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). IOP and baseline RNFL thickness were unaffected by conbercept treatment. P1 amplitude density was significantly higher 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). None of the 40 eyes showed obvious ocular adverse reactions, such as endophthalmitis, glaucoma, cataract progression, and retinal detachment, and none of the patients experienced systemic adverse events, such as cardiovascular and cerebrovascular accidents.
CONCLUSIONS
Intravitreal injection of conbercept is beneficial to eyes with ICNV, inducing the recovery of macular structure and function and improving BCVA, while not damaging the neuroretina. Intravitreal conbercept is safe and effective for the treatment of ICNV.
Topics: Humans; Intravitreal Injections; Vascular Endothelial Growth Factor A; Retrospective Studies; Choroidal Neovascularization; Retina; Tomography, Optical Coherence; Retinal Detachment; Angiogenesis Inhibitors; Treatment Outcome; Fluorescein Angiography; Recombinant Fusion Proteins
PubMed: 38373901
DOI: 10.1186/s12886-024-03344-6 -
Journal of Thoracic Disease May 2024Vascular rings represent 1% of congenital cardiovascular abnormalities. Phenotypic expression varies from asymptomatic to severe forms related to either oesophageal or...
BACKGROUND
Vascular rings represent 1% of congenital cardiovascular abnormalities. Phenotypic expression varies from asymptomatic to severe forms related to either oesophageal or tracheal compression. While refinement in prenatal screening led to an increase in fetal diagnosis, optimal management in asymptomatic neonates and infants is currently a matter of debate. We report our center experience of vascular ring management over three decades.
METHODS
In this single-center retrospective study, data were extracted from patient medical records. To obtain information on symptoms/medication at follow-up, clinical records from pediatric clinics were reviewed. For patients followed in other institutions, a web-based questionnaire was sent to referring pediatricians.
RESULTS
Out of 82 patients, 69 were symptomatic (84%). Common symptoms included recurrent respiratory tract infections (43%), stridor (32%), gastro-esophageal reflux (33%), and dysphagia (26%). Diagnosis relied on cardiac ultrasound, barium swallow studies, and chest computerized tomography scan. Surgical repair (thoracotomy 91%) was performed in 79 patients (96%). Median age at repair was 13 [interquartile range (IQR), 4.4-48] months. There was no mortality. Minor complications occurred in 14 patients (18%). Median hospital length of stay was 7 (IQR, 6-9) days. In total, 24% of patients remained symptomatic (median follow-up 54 months). Half of those were asthma-related, with nearly 90% freedom from ring-related symptoms.
CONCLUSIONS
Most patients were symptomatic at the time of diagnosis. Vascular rings such as pulmonary slings or tracheal compression syndromes require prompt management. Despite surgery, 24% of patients were not symptom-free at follow-up. Finally, surgery in asymptomatic patients resulted in low morbidity supporting the current recommendation of early surgical repair.
LEVEL OF EVIDENCE
III.
PubMed: 38883675
DOI: 10.21037/jtd-23-1526 -
Applied Microbiology and Biotechnology Jan 2024Fibronectin (FN) and collagen are vital components of the extracellular matrix (ECM). These proteins are essential for tissue formation and cell alignment during the...
Fibronectin (FN) and collagen are vital components of the extracellular matrix (ECM). These proteins are essential for tissue formation and cell alignment during the wound healing stage. In particular, FN interacts with collagens to activate various intracellular signaling pathways to maintain ECM stability. A novel recombinant extra domain-B fibronectin (EDB-FN)-COL3A1 fusion protein (rhFEB) was designed to mimic the ECM to promote chronic and refractory skin ulcer wound healing. rhFEB significantly enhanced cell adhesion and migration, vascular ring formation, and the production of new collagen I (COL1A1) in vitro. rhFEB decreased M1 macrophages and further modulated the wound microenvironment, which was confirmed by the treatment of db/db mice with rhFEB. Accelerated wound healing was shown during the initial stages in rhFEB-treated db/db mice, as was enhanced follicle regeneration, re-epithelialization, collagen deposition, granulation, inflammation, and angiogenesis. The wound chronicity of diabetic foot ulcers (DFUs) remains the main challenge in current and future treatment. rhFEB may be a candidate molecule for regulating M1 macrophages during DFU healing. KEY POINTS: • A recombinant protein EDB-FN-collagen III (rhFEB) was highly expressed in Escherichia coli • rhFEB protein induces COL1A1 secretion in human skin fibroblasts • rhFEB protein accelerates diabetic wound healing.
Topics: Humans; Animals; Mice; Fibronectins; Skin; Wound Healing; Extracellular Matrix; Escherichia coli; Collagen
PubMed: 38285241
DOI: 10.1007/s00253-024-13021-9 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Oct 2023To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic...
OBJECTIVE
To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis.
METHODS
Between February 2017 and January 2020, 11 patients with aseptic loosening or screw fracture of modular hemi-pelvic prosthesis were revised using 3D-printed hemi-pelvic prostheses. There were 7 males and 4 females with an average age of 44 years (range, 25-60 years). In the first operation, all patients underwent total tumor resection, modular hemi-pelvic prosthesis reconstruction, and autologous femoral head transplantation. According to the Enneking pelvic partition system, 8 cases were resected in zones Ⅰ+Ⅱ and 3 cases in zones Ⅰ+Ⅱ+Ⅲ. The interval from the initial operation to this revision ranged from 14.3-66.2 months, with an average of 35.8 months. The operation time, the amount of intraoperative bleeding, and the occurrence of complications were recorded. At 6 months after the first operation, before revision, and at last follow-up, the American Musculoskeletal Tumor Society (MSTS) score and Harris score were used to evaluate the recovery of lower limb function. The pain-free walking distance of patients without brace assistance was recorded at last follow-up. X-ray films were taken at 1 month after the first operation, before revision, and at 1 month after revision, the acetabulum position was assessed by the differences in weight arm and cup height between bilateral hip joints. At last follow-up, the digital X-ray tomography was taken to evaluate the prosthesis-bone integration and the occurrence of aseptic loosening.
RESULTS
The operation time was 182.6-238.0 minutes (mean, 197.4 minutes). The amount of intraoperative bleeding was 400-860 mL (mean, 550.0 mL). All incisions healed by first intention with no infection, hip dislocation, nerve damage, or vascular-related adverse events. The MSTS score and Harris score at last follow-up were significantly higher than those at 6 months after the first operation and before revision ( <0.05), while the score before revision was significantly lower than that at 6 months after the first operation ( <0.05). At last follow-up, the patients were able to walk more than 1 000 meters painlessly without brace assistance. Imaging review showed that the difference of cup height at 1 month after revision was significantly lower than that at 1 month after the first operation and before revision, and at 1 month after the first operation than before revision operation, and the differences were significant ( <0.05). There was no significant difference in the difference of weight arm among three time points ( >0.05). All prostheses were well integrated, and no aseptic loosening of the prosthesis or screw fracture occurred.
CONCLUSION
Revision with 3D-printed hemi-pelvic prostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. Early postoperative rehabilitation training can maximize the recovery of patient limb function, reduce pain during walking, and reduce the incidence of complications.
Topics: Male; Female; Humans; Adult; Arthroplasty, Replacement, Hip; Hip Prosthesis; Treatment Outcome; Prosthesis Failure; Fractures, Bone; Retrospective Studies; Neoplasms
PubMed: 37848311
DOI: 10.7507/1002-1892.202306073 -
BioRxiv : the Preprint Server For... Apr 2024Cerebral amyloid angiopathy (CAA) is a vasculopathy characterized by vascular β-amyloid (Aβ) deposition on cerebral blood vessels. CAA is closely linked to Alzheimer's...
Cerebral amyloid angiopathy (CAA) is a vasculopathy characterized by vascular β-amyloid (Aβ) deposition on cerebral blood vessels. CAA is closely linked to Alzheimer's disease (AD) and intracerebral hemorrhage. CAA is associated with the loss of autoregulation in the brain, vascular rupture, and cognitive decline. To assess morphological and molecular changes associated with the degeneration of penetrating arterioles in CAA, we analyzed post-mortem human brain tissue from 26 patients with mild, moderate, and severe CAA end neurological controls. The tissue was optically cleared for three-dimensional light sheet microscopy, and morphological features were quantified using surface volume rendering. We stained Aβ, vascular smooth muscle (VSM), lysyl oxidase (LOX), and vascular markers to visualize the relationship between degenerative morphological features, including vascular dilation, dolichoectasia (variability in lumenal diameter) and tortuosity, and the volumes of VSM, Aβ, and LOX in arterioles. Atomic force microscopy (AFM) was used to assess arteriolar wall stiffness, and we identified a pattern of morphological features associated with degenerating arterioles in the cortex. The volume of VSM associated with the arteriole was reduced by around 80% in arterioles with severe CAA and around 60% in cases with mild/moderate CAA. This loss of VSM correlated with increased arteriolar diameter and variability of diameter, suggesting VSM loss contributes to arteriolar laxity. These vascular morphological features correlated strongly with Aβ deposits. At sites of microhemorrhage, Aβ was consistently present, although the morphology of the deposits changed from the typical organized ring shape to sharply contoured shards with marked dilation of the vessel. AFM showed that arteriolar walls with CAA were more than 400% stiffer than those without CAA. Finally, we characterized the association of vascular degeneration with LOX, finding strong associations with VSM loss and vascular degeneration. These results show an association between vascular Aβ deposition, microvascular degeneration, and increased vascular stiffness, likely due to the combined effects of replacement of VSM by β-amyloid, cross-linking of extracellular matrices (ECM) by LOX, and possibly fibrosis. This advanced microscopic imaging study clarifies the association between Aβ deposition and vascular fragility. Restoration of physiologic ECM properties in penetrating arteries may yield a novel therapeutic strategy for CAA.
PubMed: 38659767
DOI: 10.1101/2024.03.08.583563 -
International Journal of Molecular... Sep 2023Cell therapies involving the administration of bone marrow-derived mononuclear cells (BM-MNCs) for patients with chronic limb-threatening ischemia (CLTI) have shown...
Cell therapies involving the administration of bone marrow-derived mononuclear cells (BM-MNCs) for patients with chronic limb-threatening ischemia (CLTI) have shown promise; however, their overall effectiveness lacks evidence, and the exact mechanism of action remains unclear. In this study, we examined the angiogenic effects of well-controlled human bone marrow cell isolates on endothelial cells. The responses of endothelial cell proliferation, migration, tube formation, and aortic ring sprouting were analyzed in vitro, considering both the direct and paracrine effects of BM cell isolates. Furthermore, we conducted these investigations under both normoxic and hypoxic conditions to simulate the ischemic environment. Interestingly, no significant effect on the angiogenic response of human umbilical vein endothelial cells (HUVECs) following treatment with BM-MNCs was observed. This study fails to provide significant evidence for angiogenic effects from human bone marrow cell isolates on human endothelial cells. These in vitro experiments suggest that the potential benefits of BM-MNC therapy for CLTI patients may not involve endothelial cell angiogenesis.
PubMed: 37762125
DOI: 10.3390/ijms241813822