Engineered Hybrid Vesicles and Cellular Internalization in Mammary Cancer Cells.

Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion method and incorporated an anticancer drug. As a result, we successfully prepared nanosized uniform hybrid vesicles and evaluated their physicochemical characteristics and intracellular uptake mechanisms via endocytosis in various cell lines. Compared to liposomes, the hybrid vesicles showed better physical properties and a relatively higher reduction in cell viability, which was presumably dependent on the specific cell type. These findings suggest that fusion-based hybrid vesicles offer a novel strategy for delivering therapeutic agents and provide insights into the types of extracellular vesicles that are useful in fabricating hybrid vesicles to develop an advanced drug delivery system.

Comparative analysis of immunotherapy responses in small cell lung cancer patients with dermatomyositis.

Cancer-associated dermatomyositis (CAD), a paraneoplastic syndrome characterized by dermatomyositis (DM), frequently presents in association with small cell lung cancer (SCLC). Although the advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, their efficacy and safety in patients with concurrent autoimmune diseases (AD) and malignancies remains uncertain. Several studies have suggested the safe administration of ICIs in patients with AD, indicating that successful cancer therapy can alleviate CAD symptoms. Conversely, other studies have raised concerns about the potential for ICIs to exacerbate AD flares or immune-related adverse events (irAEs). A comparative analysis of two cases from our institution emphasizes the variability in ICI responses among SCLC patients with CAD. One patient, previously reported as a case study, exhibited significant clinical improvement in DM symptoms after ICI administration, whereas the other developed severe exfoliative skin changes and experienced an unfavorable prognosis. This variability emphasizes the need for careful patient selection and close monitoring during ICI treatment. We hypothesized that overweight or obese individuals and those with severe initial skin lesions and elevated lactate dehydrogenase levels are more susceptible to developing irAEs following ICI therapy. Therefore, caution is advised when considering immunotherapy in these patients.

A patient with a lung adenosquamous carcinoma harboring a de novo T790M mutation and huge nonbacterial vegetative growths successfully treated with osimertinib: A case report.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition; sterile vegetations attach to heart valves. NBTE is typically found in patients with malignancies or autoimmune disorders. Although surgical interventions are sometimes performed, the appropriate indication and timing are still unclear. Here, we describe a 72-year-old woman diagnosed with adenosquamous carcinoma of the lung. She was initially diagnosed as pT2aN0M0 and underwent RUL lobectomy. After nine months, lung cancer recurred, and she underwent treatment with cytotoxic chemotherapy. However, images showed progression after only one month. Rebiopsy revealed she had comutation of de novo EGFR L858R and T790M. Treatment was changed to gefitinib. After one month, she experienced loss of consciousness. Brain magnetic resonance imaging (MRI) showed multiple lesions resembling infarctions or metastases. Chest computed tomography (CT) revealed progression. Osimertinib was prescribed and she underwent echocardiography to rule out the possibility of a cardiogenic embolism. Surprisingly, severe mitral regurgitation and a massive vegetation on the mitral valve were found. Cardiologists recommended surgery due to the severity of the embolic event and valve dysfunction, but it was decided to continue antibiotics, osimertinib, and anticoagulants instead of surgery due to the patient's poor general condition and the possibility of NBTE. Six weeks later, the patient's condition markedly improved and echocardiography revealed a marked reduction in vegetation size. Clinicians should be aware that targeted therapy can be effective in treating severe cancer complications, such as NBTE, as evidenced by the successful treatment of lung cancer with osimertinib. This option should be considered, particularly for elderly lung cancer patients, before resorting to surgery as a first-line treatment for NBTE.

Mass Lesions That Almost Fill the Ascending Aorta: When to Operate?

Although anticoagulation can be an option for the resolution of thrombus, surgical removal is a definite treatment for removing mass lesions, especially in patients with unknown pathology. The present case report demonstrates the surgical removal of a sarcoma of the ascending aorta after the failure of anticoagulation. (Level of Difficulty: Advanced.).

Cesarean scar pregnancy; Diagnosis and management between 2003 and 2015 in a single center.

OBJECTIVES: We aimed to evaluate diagnosis and management of an ectopic pregnancy developing in a previous cesarean scar. MATERIALS AND METHODS: Between March 2003 and October 2015, total 64 cases of cesarean scar pregnancy (CSP) were retrospectively reviewed. The cliniscal characteristics, diagnosis, various methods of treatment and clinical outcomes were analyzed. RESULTS: The mean gestational age at diagnosis was 6.5 ± 1.1 weeks and the number of previous cesarean section was 1.6 ± 0.6. The main ultrasonographic findings included anterior implantation of gestational sac within the previous CS scar and thinning of anterior myometrium (average: 3.0 ± 2.0 mm). Excluding 6 cases that were lost to follow up after diagnosis, 58 patients underwent first line treatment. The treatment was successful with first line therapy alone in 32 patients (55.2%). Emergency hysterectomy was necessary in 4 cases during following up of first line treatment. In 22 patients who underwent second line treatment, all of them were successfully treated with no additional treatment. CONCLUSIONS: MTX treatment alone as first line treatment showed low success rate (41.3%). Wedge resection (100%) and hysteroscopy (66.7%) were relatively safe and they were the most successful treatment modalities in this study. Dilatation and curettage as first and second line treatment had about 20% and 16.7% risk of emergency hysterectomy due to severe hemorrhage respectively. Therefore, surgical modalities with direct visualization excluding dilatation and curettage seem to be more safe and successful than medical treatment using MTX alone. Early precise diagnosis and management of CSP will be very important to minimize the extent of treatment and thus improve clinical outcomes of the patients.

Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage.

Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy (p = 0.042) and showed tendency for improving functional recovery (p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage.

Wearable, wireless gas sensors using highly stretchable and transparent structures of nanowires and graphene.

Herein, we report the fabrication of a highly stretchable, transparent gas sensor based on silver nanowire-graphene hybrid nanostructures. Due to its superb mechanical and optical characteristics, the fabricated sensor demonstrates outstanding and stable performances even under extreme mechanical deformation (stable until 20% of strain). The integration of a Bluetooth system or an inductive antenna enables the wireless operation of the sensor. In addition, the mechanical robustness of the materials allows the device to be transferred onto various nonplanar substrates, including a watch, a bicycle light, and the leaves of live plants, thereby achieving next-generation sensing electronics for the 'Internet of Things' area.

Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor ß positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

Antioxidant Effects of Spinach (Spinacia oleracea L.) Supplementation in Hyperlipidemic Rats.

Increased consumption of fresh vegetables that are high in polyphenols has been associated with a reduced risk of oxidative stress-induced disease. The present study aimed to evaluate the antioxidant effects of spinach in vitro and in vivo in hyperlipidemic rats. For measurement of in vitro antioxidant activity, spinach was subjected to hot water extraction (WE) or ethanol extraction (EE) and examined for total polyphenol content (TPC), oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA), and antigenotoxic activity. The in vivo antioxidant activity of spinach was assessed using blood and liver lipid profiles and antioxidant status in rats fed a high fat-cholesterol diet (HFCD) for 6 weeks. The TPC of WE and EE were shown as 1.5±0.0 and 0.5±0.0 mg GAE/g, respectively. Increasing the concentration of the extracts resulted in increased ORAC value, CAA, and antigenotoxic activity for all extracts tested. HFCD-fed rats displayed hyperlipidemia and increased oxidative stress, as indicated by a significant rise in blood and liver lipid profiles, an increase in plasma conjugated diene concentration, an increase in liver thiobarbituric acid reactive substances (TBARS) level, and a significant decrease in manganese superoxide dismutase (Mn-SOD) activity compared with rats fed normal diet. However, administration of 5% spinach showed a beneficial effect in HFCD rats, as indicated by decreased liver TBARS level and DNA damage in leukocyte and increased plasma conjugated dienes and Mn-SOD activity. Thus, the antioxidant activity of spinach may be an effective way to ameliorate high fat and cholesterol diet-induced oxidative stress.