Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton-Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment.

The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.

Synergized photothermal therapy and magnetic field induced hyperthermia via bismuthene for lung cancer combinatorial treatment.

Thanks to its intrinsic properties, two-dimensional (2D) bismuth (bismuthene) can serve as a multimodal nanotherapeutic agent for lung cancer acting through multiple mechanisms, including photothermal therapy (PTT), magnetic field-induced hyperthermia (MH), immunogenic cell death (ICD), and ferroptosis. To investigate this possibility, we synthesized bismuthene from the exfoliation of 3D layered bismuth, prepared through a facile method that we developed involving surfactant-assisted chemical reduction, with a specific focus on improving its magnetic properties. The bismuthene nanosheets showed high in vitro and in vivo anti-cancer activity after simultaneous light and magnetic field exposure in lung adenocarcinoma cells. Only when light and magnetic field are applied together, we can achieve the highest anti-cancer activity compared to the single treatment groups. We have further shown that ICD-dependent mechanisms were involved during this combinatorial treatment strategy. Beyond ICD, bismuthene-based PTT and MH also resulted in an increase in ferroptosis mechanisms both in vitro and in vivo, in addition to apoptotic pathways. Finally, hemolysis in human whole blood and a wide variety of assays in human peripheral blood mononuclear cells indicated that the bismuthene nanosheets were biocompatible and did not alter immune function. These results showed that bismuthene has the potential to serve as a biocompatible platform that can arm multiple therapeutic approaches against lung cancer.

Ocular pharmacokinetics and toxicity of nanoparticular acetazolamide: In vivo distribution and safety of PHBV-ACZ nanoparticle.

Diabetic macular edema (DME) is defined as fluid accumulation in the macular region, between the retinal layers, due to many diseases, especially diabetes. DME is one of the major complications of diabetic retinopathy (DRP). Carbonic anhydrase inhibitors (CAI) are a pharmaceutical agent used in different fields, especially glaucoma treatment. Acetazolamide (ACZ), which is a CAI, is an active substance that has been used off-label for many years in the treatment of macular edema due to diabetes and many other diseases. The low solubility and bioavailability of ACZ limit its use in the treatment of DME. In this study, a nanoparticulate formulation was developed that would increase the solubility and bioavailability of ACZ and allow it to be administered intravitreally. ACZ was loaded on poly(3-hydroxybutyrate-co-3-Hydroxyvalerate) (PHBV) nanoparticles and the loading efficiency was 71.58 ± 1.22%. Toxicity of nanoparticles after intravitreal application was evaluated with anterior segment and posterior segment examination findings, intraocular pressure (IOP) measurements and electrophysiological tests. At the end of the 3-month follow-up, electroretinography (ERG) measurements demonstrated that ACZ loaded PHBV (PHBV-ACZ) nanoparticles did not cause loss of function in retinal cells. On histological examination, rare degenerative changes were observed in several cell groups. In addition, pharmacokinetic studies were performed to determine the tissue distribution of ACZ at various periods. ACZ was identified in vitreous humor and retina at the highest concentration. Based on our results, the prepared nanoparticle formulation can release long-term CAI for DRP therapy and accordingly can reduce the need for monthly intravitreal injections.

Magnetic resonance imaging, computed tomography, and gross anatomy of forelimb joints in New Zealand rabbit (Oryctolagus cuniculus L.).

The present study aimed to define the anatomical structures by comparing the transversal computed tomography (CT) and magnetic resonance (MR) images of the forelimb joints of the rabbits with the cross-sectional plastinated images. A total of 14 (seven females, seven males) one-year-old adult New Zealand rabbits were used in the study. After the CT and MR imaging procedures were completed, the forelimbs were removed from the body. The forelimbs were plastinated using the silicone plastination method and sectioned transversal. Cross-sectional plastinates were evaluated and correlated anatomically with conjugate CT and MR images. Joint and surrounding anatomical structures were defined in sections. Cross-sectional plastinated samples were highly correlated with CT and MR images in terms of bone and soft tissue, respectively. It is thought that the anatomical and radiological data obtained from the forelimb joints of rabbits will provide a basis for scientists who are involved in both experimental surgical interventions and clinical anatomy education.

Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration - An in vitro and in vivo evaluation.

Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro - in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.

Anatomical study of the scleral ring and eyeball of the long-eared owl (Asio otus) with anatomical methods and diagnostic imaging techniques.

BACKGROUND: The scleral ring in birds consists of ossicles that are fixed as small plates by cartilage joints and have no articulation to other parts of the skeleton. OBJECTIVE: Due to inadequate examination of the scleral ring anatomy and its specific form in owls, this study aimed to investigate the exact structure of the scleral ring and some morphometric characteristics of the eyeball in a long-eared owl (Asio otus). METHODS: The eyes of 20 alive and 10 dead male and female owls were examined. In addition to common anatomical methods, computed tomography scans and radiographic and ultrasonographic imaging techniques were used in this study. RESULTS: The structure consisted of 15 ossicles. In the ventral part of the ring, these tubercles were observed in the scleral rings of all owls; in each ring, there were four bones with these tubercles. Additionally, there was no significant difference between the left and right eye parameters. Most ocular parameters in female owls were larger than those in males, but in the case of some parameters, such as optic nerve length and optic nerve sheath diameter, this difference was not observed. CONCLUSIONS: According to this study, the scleral ring in the Asio otus has anterior and posterior parts, and the lens is in the immediate vicinity of the anterior part. The right and left scleral rings and eyeballs are bilaterally symmetrical in terms of the shape, size, and number of ossicles that form the ring.

Morphological pattern of the pes tendons in Bennett's Wallaby (Macropus rufogriseus).

Wallabies are small- to medium-sized hopping marsupials and have large and flexible tendons in their hind limbs that act like springs. This study aimed to show the morphological pattern of the pes tendons in Bennett's wallaby. Two Bennett's Wallabies (Macropus rufogriseus) that died of natural causes have been used for this study. The pes was dissected using standard dissection techniques to expose the tendons around metatarsals and digits. The crural musculature of the hind limb was also dissected to identify the origin of the tendons. Tendons of m. extensor digitorum longus, m. extensor digitorum lateralis, m. extensor digiti II et III longus, m. flexor digitorum superficialis, m. flexor digitorum profundus and mm. interossei were the main identified tendons. Tendons of m. extensor digitorum longus attached to the distal phalanx of the fourth digit. The tendon of m. extensor digitorum lateralis had two insertion points, on the fourth and the fifth digits. The tendon of m. flexor digitorum superficialis bifurcates at the level proximal one-third of the metatarsus. The relatively thinner branch inserted into the phalanx of the fifth digit, while the thicker splits and inserted to the medial and lateral surface of the distal end of the proximal phalanx of the fourth digit. Tendon of m. flexor digitorum profundus was the thickest tendon on the plantar surface, and it had four insertion points, which were the distal phalanges of the second, third, fourth and fifth digits. This study provides detailed information for future studies on the biomechanical and functional morphology of tendons in marsupials.

Clinicopathological and immunohistochemical evaluation of lonidamine-entrapped lipid-polymer hybrid nanoparticles in treatment of benign prostatic hyperplasia: An experimental rat model.

Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine - the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment - was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid-polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the hepatic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.

Photocatalytically Active Graphitic Carbon Nitride as an Effective and Safe 2D Material for In Vitro and In Vivo Photodynamic Therapy.

Thanks to its photocatalytic property, graphitic carbon nitride (g-C3 N4 ) is a promising candidate in various applications including nanomedicine. However, studies focusing on the suitability of g-C3 N4 for cancer therapy are very limited and possible underlying molecular mechanisms are unknown. Here, it is demonstrated that photoexcitation of g-C3 N4 can be used effectively in photodynamic therapy, without using any other carrier or additional photosensitizer. Upon light exposure, g-C3 N4 treatment kills cancer cells, without the need of any other nanosystem or chemotherapeutic drug. The material is efficiently taken up by tumor cells in vitro. The transcriptome and proteome of g-C3 N4 and light treated cells show activation in pathways related to both oxidative stress, cell death, and apoptosis which strongly suggests that only when combined with light exposure, g-C3 N4 is able to kill cancer cells. Systemic administration of the mesoporous form results in elimination from urinary bladder without any systemic toxicity. Administration of the material significantly decreases tumor volume when combined with local light treatment. This study paves the way for the future use of not only g-C3 N4 but also other 2D nanomaterials in cancer therapy.

Comparative evaluation of anatomic structures in regio manus and regio pedis on computed tomography images and plastinated cross-sections of horse / Evaluación comparativa de estructuras anatómicas en regio manus y 1 en imágenes de tomografía computarizada y cortes transversales plastinados de caballos

SUMMARY: Movement analysis of horses is closely related to the bone, joint and muscle composition. Equine foot is quiet important not only for veterinarians, but also for farmers and horseshoer. In this study, it is aimed to evaluate and compare the anatomical structures of equine foot obtained from computed tomography images and S10B silicone plastinated sections of horse and 3 dimensional images of related structures as well. Four adult horses were used in this study. Computed tomography images were acquired in a proper position for equine feet. Then S10B silicone plastination was performed for the same specimens. Plastinates were sliced into 1 cm sections, corresponding to the computed tomography images. The sections obtained from silicone plastination were found to be compatible with computed tomography images. It was seen that osseous structures and tendons were clearly identified on computed tomography images. It was observed that the shrinkage on the osseous tissues was very limited. It was thought that the proportional differences between the plastinated specimens and computed tomography images were related with the fixation process. The specimens plastinated with S10B silicone polymer was determined to be closer to natural colour when compared to the standard polymers. Therefore it was found to be more useful. It is considered that plastinates can be effectively used in veterinary orthopaedics and radiology trainings as well as in veterinary anatomy education.

RESUMEN: El análisis del movimiento de los caballos está estrechamente relacionado con la composición ósea, articular y muscular. El pie equino es muy importante no solo para los veterinarios, sino también para los agricultores y herradores. El objetivo de este trabajo consistió en evaluar y comparar las estructuras anatómicas del pie equino obtenidas a partir de imágenes de tomografía computarizada y secciones plastinadas con silicona S10B y también con imágenes tridimensionales de estructuras relacionadas. Cuatro caballos adultos fueron utilizados en este estudio. Las imágenes de tomografía computarizada se adquirieron en una posición adecuada para los pies equinos. Luego se realizó plastinación con silicona S10B para las mismas muestras. Los plastinados se cortaron en secciones de 1 cm, correspondientes a las imágenes de tomografía computada. Las secciones obtenidas de plastinación con silicona fueron compatibles con las imágenes de tomografía computarizada. Se observó que las estructuras óseas y los tendones estaban claramente identificados en las imágenes de tomografía computarizada. Se observó que la contracción de los tejidos óseos era muy limitada. Se pensó que las diferencias proporcionales entre las muestras plastinadas y las imágenes de tomografía computada estaban relacionadas con el proceso de fijación. Se determinó que las muestras plastinadas con polímero de silicona S10B se presentaron con un color más cercano al natural en comparación con los polímeros estándar. Por lo tanto, se encontró que fue más útil. Se considera que los plastinados se pueden utilizar eficazmente en ortopedia veterinaria y capacitación en radiología, así como en educación en anatomía veterinaria.

Sectional evaluation of anatomic structures in cat (Felis catus) thoracic cavity by computed tomography imaging and silicone plastination methods / Evaluación seccional de estructuras anatómicas de la cavidad torácica en gato (Felis catus) con imágenes de tomografía computada y métodos de plastinación de silicona

It was aimed to determine the anatomical structures in thoracic cavity by computed tomography imaging (CT) and compare the cross sectional images in the same specimens which were plastinated after CT imaging. It was also aimed to obtain 3 dimensional (3D) reconstructions of thoracic anatomical structures. Thoracic organs of 3 adult cats were CT imaged and then plastinated in this study. Specimens were plastinated in the same body position in the CT imaging process. CT images and corresponding plastinated cross sections were compared to each other. Anatomical structures of the thoracic cavity in plastinates were in accordance with CT images. Beside the bony structures, other organs such as esophagus, trachea, heart with related vessels, lungs and thoracic muscles were well defined in CT images and plastinates. Moreover, 3D reconstructed images of anatomical structures of thoracic cavity were acquired well. This study is thought to be beneficial for veterinary surgery and radiology fields as well as veterinary anatomy educations.

El objetivo de este trabajo consistió en determinar las estructuras anatómicas en la cavidad torácica mediante tomografía computarizada (TC) y comparar las imágenes transversales en las mismas muestras, que fueron plastinadas después de la TC. También se pretendía obtener reconstrucciones tridimensionales (3D) de estructuras anatómicas torácicas. Se tomaron imágenes de los órganos torácicos de 3 gatos adultos por TC y luego se plastinaron en este estudio. Las muestras se plastinaron en la misma posición corporal en el proceso de obtención de imágenes TC. Las imágenes de TC y las secciones transversales plastinadas correspondientes se compararon entre sí. Las estructuras anatómicas de la cavidad torácica en los preparados plastinados estaban de acuerdo con las imágenes de CT. Además de las estructuras óseas, otros órganos como el esófago, la tráquea, el corazón con vasos relacionados, los pulmones y los músculos torácicos estaban bien definidos en las imágenes de TC y los plastinados. Por otra parte, se captaron bien las imágenes reconstruidas en 3D de las estructuras anatómicas de la cavidad torácica. Pensamos que este estudio es beneficioso para la cirugía veterinaria y los campos de radiología, así como también para la educación de anatomía veterinaria.

The preventive role of transurethral antibiotic delivery in a rat model.

PURPOSE: There is currently an emerging need for developing improved approaches for preventing urinary tract infections (UTIs) occurring during diagnostic or interventional procedures of the lower urinary tract. We aimed to establish a rat model to assess the use of transurethral antibiotic administration and to provide evidence that this could be used as a preventive therapy. METHODS: Animals received fosfomycin trometamol (FOF) either urethrally or orally prior to the procedure. A third group was generated as treatment controls and did not receive any medication. Urethral dilation was conducted to recapitulate an interventional procedure prior to intravesical Escherichia coli administration in all three groups. Finally, sham-operated animals were introduced as a fourth group which did not receive antibiotics or E. coli. Colony counts of urine and tissue cultures for the identification of E. coli and histopathological examinations of the bladder and prostate were conducted. RESULTS: Evaluation of infection intensities in cultures as well as histopathological examination of the bladder and prostate demonstrated a preventative role of transurethral FOF administration. In terms of efficiency, local administration of FOF was similar to oral administration. CONCLUSIONS: These results suggest that transurethral antibiotic administration is a promising alternative for preventing UTIs occurring during diagnostic or interventional procedures of the lower urinary tract.