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Advanced Healthcare Materials Oct 2023Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced...
Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after Lu labeling. Among them, Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.
Topics: Humans; Animals; Mice; Rabbits; Carcinoma, Hepatocellular; Liver Neoplasms; Microspheres; Radioisotopes; Immunotherapy; Tumor Microenvironment
PubMed: 37235739
DOI: 10.1002/adhm.202300944 -
Journal of Nanobiotechnology Aug 2023The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin...
BACKGROUND
The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (I/I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin.
RESULTS
SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism.
CONCLUSION
The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.
Topics: Animals; Mice; Rabbits; Rats; Fibroins; Gold; Positron Emission Tomography Computed Tomography; Metal Nanoparticles; Arteries; Doxorubicin
PubMed: 37598140
DOI: 10.1186/s12951-023-02032-9 -
Journal of Veterinary Dentistry Dec 2023The anatomy of the stomatognathic system is important for both clinical evaluations and surgical approaches in all animal species. The aim of this study was to describe...
The anatomy of the stomatognathic system is important for both clinical evaluations and surgical approaches in all animal species. The aim of this study was to describe the innervation and vascularization of the stomatognathic system of the dog. Twelve dogs without a history of disease or cranial malformation were used: 4 brachycephalic, 4 mesocephalic, and 4 dolichocephalic. The dogs were dissected, and arteries, veins, and nerves related to the masticatory and swallowing components were identified. The distribution pattern of these structures in the 3 different skull types were observed. The entire blood supply of the stomatognathic system is derived from the external carotid artery, which originates from the common carotid artery, and terminates as it branches into the superficial temporal and maxillary arteries. The other main branches of the common carotid artery are the occipital, cranial laryngeal, ascending pharyngeal, lingual, facial, caudal auricular, and parotid arteries. Blood drainage was achieved via the external jugular vein, which originates from the union of the linguofacial and maxillary veins. Brachycephalic dogs had blood vessels with greater sinuosity (more deviations) when compared to dolichocephalic and mesocephalic dogs. The stomatognathic system innervation of brachycephalic skull dogs showed differences in the distribution of the facial nerve in the labial commissure and maxillary and mandibular regions. The cranial conformation of dogs demonstrated anatomical variations of the vascular and neural structures of the stomatognathic system. This data may be useful to improve clinical practice, surgical planning, and interpretation of clinical dysfunctions.
Topics: Dogs; Animals; Skull; Stomatognathic System
PubMed: 37499187
DOI: 10.1177/08987564231176021 -
BMC Cardiovascular Disorders Nov 2023The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart...
BACKGROUND
The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery.
METHODS
150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio.
RESULTS
Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000).
CONCLUSIONS
This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.
Topics: Humans; Male; Female; Myofibrils; Testosterone; Estradiol; Coronary Artery Bypass; Gonadal Steroid Hormones
PubMed: 37925416
DOI: 10.1186/s12872-023-03582-4 -
Clinical Neurology and Neurosurgery Aug 2023Transvenous onyx (Microtherapeutics, Irvine, CA, USA) embolization with sinus reconstruction using a venous balloon is a novel technique to embolise dural arterial...
Transvenous onyx (Microtherapeutics, Irvine, CA, USA) embolization with sinus reconstruction using a venous balloon is a novel technique to embolise dural arterial venous fistula while preserving the sinus. We elucidate the technical tips and tricks that were employed to treat this torcular dural AVF in an elderly male with visual disturbances secondary to papilledema. Right external carotid artery injection revealed a type 2c fistula along the torcula with feeders from the right parietal & petrosal branches of the middle meningeal artery and dural branches of the posterior auricular and the occipital artery. The right distal transverse and the sigmoid were occluded with retrograde flow into the superior sagittal sinus and the cortical veins. XPER CTA analysis revealed the fistula point to be along the wall of the torcula. Through right femoral artery access, a neuron max (Penumbra inc.USA) was placed in the right common carotid artery. An eclipse (Balt Extrusion, France) 6 × 12 mm single lumen balloon was placed in the proximal ECA to achieve flow reduction. Thereafter, through bilateral femoral venous approach, two neuron max 8 F (Penumbra inc.USA) were placed into the left jugular vein. A Copernic RC balloon 10×80 mm (Balt Extrusion, France) was placed from the left to the right transverse sinus. Further, two microcatheters, 1.5 F Marathon (Medtronic, Minneapolis, MI, USA) were navigated into the feeding arteries from the venous end. Microcatheter injections were taken with inflation of the venous balloon to determine the point at which sinus and cortical vein reflux is absent. Following that onyx 18 was injected under biplane fluoroscopy with an adequately inflated arterial and venous balloon. We could achieve retrograde permeation of the onyx into the fistula and the arterial feeders resulting in complete occlusion while preserving the sinus. Careful analysis of the angioarchitecture of the fistula and evaluating for delayed cerebral venous drainage is the key to determining the right strategy to achieve complete occlusion of the fistula.
Topics: Humans; Male; Aged; Central Nervous System Vascular Malformations; Embolization, Therapeutic; Cerebral Veins; Transverse Sinuses; Arteries
PubMed: 37352678
DOI: 10.1016/j.clineuro.2023.107795