The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

BACKGROUND: Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination. RESULTS: The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. CONCLUSIONS: The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model

Modifying effect of the serum level of brain-derived neurotrophic factor (BDNF) on the association between BDNF methylation and long-term cardiovascular outcomes in patients with acute coronary syndrome

IntroductionThis study investigated the potential modifying effects of the serum brain-derived neurotrophic factor (sBDNF) level on the association between BDNF methylation status and long-term cardiovascular outcomes in acute coronary syndrome (ACS) patients.MethodsFrom 2006 to 2012, hospitalized ACS patients were consecutively recruited. The sBDNF level and BDNF methylation status were assessed at baseline in 969 patients who were followed up for major adverse cardiac events (MACEs) over 5–12 years, until 2017 or death. Cox proportional hazards models were utilized to compare the time to first composite or individual MACEs between individuals with lower and those with higher average BDNF methylation levels in the low and high sBDNF groups, respectively. The modifying effects of the sBDNF and average BDNF methylation levels on first composite and individual MACEs were analyzed using Cox proportional hazards models after adjusting for potential covariates.ResultsIn the low sBDNF group, a higher average BDNF methylation level was linked to an increase in composite MACEs independent of confounding variables, but not in the high sBDNF group [HR (95 percent CI) = 1.04 (0.76–1.44)]. The interaction effect between the sBDNF and average BDNF methylation levels on composite MACEs was significant after adjusting for covariates (P = 0.008).ConclusionCombining the BDNF methylation status and sBDNF levels may help identify ACS patients who are likely to have unfavorable clinical outcomes

A Case of a Subepidermal Calcified Nodule on the Sole without Trauma

Subepidermal calcified nodule is an uncommon form of calcinosis cutis, which most commonly occurs in children. It usually presents as an asymptomatic, solitary verrucous nodule on the head and neck region, but occasionally as multiple lesions. Serum calcium and phosphorus levels are usually normal. Histopathology shows well-formed homogeneous eosinophilic material and granules in the upper dermis. Material in the dermis stained with von Kossa was positive. We report on an unusual case of a subepidermal calcified nodule occurring on the sole. A 21-month-old male presented with an oval-shaped, whitish, hard nodule measuring 5×5 mm on the left sole, without any previous history of trauma

Treatment of Atopic Dermatitis with a Low-histamine Diet

Atopic dermatitis (AD) has numerous trigger factors. The question of whether foods can aggravate AD remains open to debate. Although a number of published papers have detailed the relationship between food allergies and AD, little research has examined the question of how food intolerance affects AD. For the purposes of this study, a six-year-old Korean boy with AD was admitted to the hospital for evaluation of the possibility of food, particularly pork, as a triggering factor in his skin disease. He had a history of worsening of symptoms when eating pork. Total serum IgE concentration was 157 IU/ml. House dust was class 2.2 (1.5 IU/ml) in MAST. All other MAST items were negative. In an oral food challenge test, he showed a positive result after eating 200 g of pork, but did not show a positive result after eating 60 g of pork. After discharge, we attempted to keep him on a balanced diet that included various types of food and prohibited him from eating food that contains a high level of histamine. After keeping the patient on a balanced and low-histamine dietary regimen, his AD symptoms showed improvement and have not worsened for more than seven months. A low-histamine, balanced diet could be helpful for AD patients having symptoms that resemble histamine intolerance in which their AD symptoms worsened after intake of histamine-rich foods, but in which food allergy tests are negative

The Effects of the Acupuncture Treatment for Smoking Cessation in High School Student Smokers

The use of alternative medicine for smoking cessation have been increasing steadily in recent years. A series of clinical group studies was performed to clarify the effect, outcome and success rate of an acupuncture treatment for smoking cessation. This study was conducted for four weeks using 238 smoking students at 2 high schools. The subjects were separated into two groups: 159 students were treated with acupuncture on the anti-smoking acupoints of the ear, which is known to be effective for cessation of smoking (case group), and 79 students were treated at other sites of the ear (control group). The acupuncture treatment was alternately administered at each side of the ears on a weekly basis for 4 weeks. The smoking cessation success was only 1 case (0.6%) in the case group and none in the control group after 4 weeks. The change in the taste of tobacco and the intensity of the desire to smoke were not significantly different between the case and control groups, but the case group showed a tendency of reduction in the taste of tobacco and the intensity of the desire to smoke. In addition, the reduction in cigarette consumption was not significant, but the tendency of reduction in the study group was significant. It is believed that the site of auricular acupuncture for smoking cessation is not important. However, there was a significant tendency in terms of the reduction in cigarette consumption, the taste of tobacco and the intensity of the desire to smoke in the case group, indicating that auricular acupuncture in smoking cessation has some effect