Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

Surgical Strategy to Reduce the Recurrence of Adventitial Cystic Disease after Treatment

PURPOSE: Adventitial cystic disease (ACD) is a rare condition that causes intermittent claudication and non-atherosclerotic disease without cardiovascular risk factors. The etiology and optimal treatment of ACD remain controversial. The purpose of this study was to analyze surgical treatment results for ACD and to elucidate optimal treatment options.MATERIALS AND METHODS: We retrospectively reviewed 30 patients with ACD who underwent surgery from 2006 to 2018. Twenty-two patients had arterial ACD, six had venous ACD, and two had combined venous and arterial ACD. We reviewed demographic and clinical characteristics, treatment details, and procedure outcomes.RESULTS: Recurrence occurred in 6 cases either after cyst excision alone (4/17) or patch angioplasty (2/2). There was no recurrence after vessel excision with interposition grafting (0/7). Therefore, vessel excision was a statistically significant factor in recurrence prevention (P=0.026). Among the six recurrences, joint connections of the cystic lesions were found in four of the six (66.7%).CONCLUSION: As a curative surgery for ACD, vessel excision with interposition grafting is a better strategy to prevent recurrence than simple cyst excision alone.

No-Touch Radiofrequency Ablation of VX2 Hepatic Tumors In Vivo in Rabbits: A Proof of Concept Study

OBJECTIVE: In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model. MATERIALS AND METHODS: Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation. RESULTS: Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group. CONCLUSION: No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.

Anti-Melanogenic Potentials of Nanoparticles from Calli of Resveratrol-Enriched Rice against UVB-Induced Hyperpigmentation in Guinea Pig Skin

We already reported that genetically engineered resveratrol-enriched rice (RR) showed to down-regulate skin melanogenesis. To be developed to increase the bioactivity of RR using calli from plants, RR was adopted for mass production using plant tissue culture technologies. In addition, high-pressure homogenization (HPH) was used to increase the biocompatibility and penetration of the calli from RR into the skin. We aimed to develop anti-melanogenic agents incorporating calli of RR (cRR) and nanoparticles by high-pressure homogenization, examining the synergistic effects on the inhibition of UVB-induced hyperpigmentation. Depigmentation was observed following topical application of micro-cRR, nano-calli of normal rice (cNR), and nano-cRR to ultraviolet B (UVB)-stimulated hyperpigmented guinea pig dorsal skin. Colorimetric analysis, tyrosinase immunostaining, and Fontana-Masson staining for UVB-promoted melanin were performed. Nano-cRR inhibited changes in the melanin color index caused by UVB-promoted hyperpigmentation, and demonstrated stronger anti-melanogenic potential than micro-cRR. In epidermal skin, nano-cRR repressed UVB-promoted melanin granules, thereby suppressing hyperpigmentation. The UVB-enhanced, highly expressed tyrosinase in the basal layer of the epidermis was inhibited by nano-cRR more prominently than by micro-cRR and nano-cNR. The anti-melanogenic potency of nano-cRR also depended on pH and particle size. Nano-cRR shows promising potential to regulate skin pigmentation following UVB exposure.

Effect of Lactobacillus gasseri BNR17 on Overweight and Obese Adults: A Randomized, Double-Blind Clinical Trial / 가정의학회지

BACKGROUND: Lactobacillus gasseri BNR17 is a type of probiotic strain isolated from human breast milk. A study was reported regarding the fact that BNR17 was an inhibitor of obesity and diabetic activities in the human body through previous animal experiments. This study was furthered to investigate the effect of BNR17, a probiotic strain isolated from human breast milk, on obese and overweight adults. METHODS: Sixty-two obese volunteers aged 19 to 60 with body mass index > or = 23 kg/m2 and fasting blood sugar > or = 100 mg/dL participated in a placebo controlled, randomized, and double-blind trial. For 12 weeks, 57 participants were given either placebo or BNR17 and were tested by measuring body fat, body weight, various biochemical parameters, vital signs, and computed tomography at the start of the study and at weeks 4, 8, and 12. The subjects assumed usual daily activities without having to make behavioral or dietary modifications during the course of the study. RESULTS: At the 12th week, a slight reduction in body weight was noted in the BNR17 group, but there were no significant weight changes between groups. Decrease of waist and hip circumferences in the BNR17 group was more pronounced than those in the placebo group. The two groups had no special or severe adverse reactions. CONCLUSION: Despite there being no change in behavior or diet, administration of only the supplement of BNR17 reduced weight and waist and hip circumference. However, there were no significant differences between the two groups. These findings warrant a subsequent longer-term prospective clinical investigation with a large population.

Breath-Hold Gadolinium-enhanced MRA: Clinical Application

PURPOSE: To compare breath-hold gadolinium enhanced MR angiography(MRA) with digital subtraction angiography. MATERIALS AND METHODS: Ten patients underwent angiography and breath-hold gadolinium enhanced MRA;the latterperformed at 1.5T with 3D FSPGR after a bolus injection of gadopentetate dimeglumine(0.4mmol/kg) RESULTS: Sevenof ten pathologic conditions(70%) evaluated by both techniques had a similar appearance. The conditions examinedwere as follows : the artery feeding renal cell carcinoma(n=2): renal artery stenosis(n=2); pulmonaryAVM(n=2);abdominal aortic aneurysm(n=1); atheromatous plaque in the lower abdominal aorta(n=1);an enlargedbronchial artery(n=1); and an aberrant renal artery(n=1). For evaluating an anatomic relationship, a reconstructed3D image obtained by MRA is more advantageous. CONCLUSION: Breath hold contrast enhanced MRA is a potentiallyuseful noninvasive screening method for detecting vascular abnormality of the aorta and its branches.

A Clinical Study of Retinopathy of Prematurity

Among 666 premature infants or low birthweight infants who were admitted in NICU of St. Francisco General Hospital from January 1990 to Jun 1992, 96 infants were diagnosed as retinopathy of prematurity by indirect ophthalmoscope. The result were follows: 1) Among 666 patients, retinopathy of prematurity developed in 96 patients(14.1%) 2) The high incidence was observed in low birthweight and small gestational age. 3) Mean age of first diagnosing time was 42.0( 12 day of life and mean gestational age was 31.8 2.5 weeks and mean birthweight was 1646.5 (350.7gm. 4) In gestational age, birthweight and duration of oxygen therapy, there was statistically difference between cryotherapy group and spontaneous regression group. Other possible risk factors-hyaline membrane disease, apnea, anemia-were showed higher incidence in cryotherapy group. 5) Among the 20 infants who were treated with cryotherapy, 16 infants (80%) showed regression of neovascularization.