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Anticancer treatment strategies using bacteria as a vector are currently expanding with the development of anticancer drugs. Here, we present a research strategy to develop anticancer drugs using bacteria that contain miRNAs. We also present a strategy for the development of novel bacterial anticancer drugs in combination with radiation. Salmonella strains expressing miRNA were produced by modifying the miRNA expression vector encoding INHA, a radiation-resistant gene developed previously. The anticancer effect of INHA was confirmed using skin cancer cell lines. We also tested a combination strategy comprising bacteria and radiation for its anticancer efficacy against radiation-resistant mouse melanoma to increase the efficacy of radiation therapy as a novel strategy. The recombinant strain was confirmed to promote effective cell death even when combined with radiation therapy, which exerts its cytotoxicity by enhancing reactive oxygen species production. Moreover, a combination of bacterial and radiation therapy enhanced radiotherapy efficacy. When combined with radiation therapy, bacterial therapy exhibited effective anti-cancer properties even when administered to animals harboring radiation-resistant tumors. This strategy may promote the secretion of cytokines in cells and more effectively reduce the number of bacteria remaining in the animal. Thus, this study may lead to the development of a strategy to improve the effectiveness of radiation therapy using Salmonella expressing cancer-specific miRNA for intractable cancers such as those resistant to radiation.

BACKGROUND Recent data suggested that dysbiosis of the gut microbiome is associated with childhood allergic diseases. Oral administration of probiotic formulations may improve the severity of atopic dermatitis (AD) by restoring imbalanced gut microbiota and reducing intestinal inflammation in children. OBJECTIVES The aim of this study was to investigate the effects of a probiotic mixture on the clinical severity of AD, gut inflammatory markers and alterations in microbiome dysbiosis in children with AD. METHODS A total of 25 subjects were enrolled in this study and administered with a mixture of probiotic strains consisting of Lactobacilli and Bifidobacteria for 4 weeks. The clinical efficacy of the probiotic mixture was assessed using SCORAD index and TEWL. Faecal calprotectin levels were measured as a marker for intestinal inflammation. The composition and diversity of the gut microbiome were analysed using 16S rRNA pyrosequencing. RESULTS The SCORAD (38.9 ± 17.2 vs 29.0 ± 15.4, P

It has been shown that aerobic exercise improves atopic dermatitis (AD), although the mechanism is not clear. Here, we propose a hypothesis that moderate-intensity aerobic exercise improves AD in a mouse model through modulating allergic inflammation. The DNCB-treated mouse model for eczema was divided into 3 groups: (a) not subjected to aerobic exercise, (b) subjected to continuous aerobic exercise and (c) subjected to accumulated aerobic exercise. After given exercise using a treadmill device either 30 min/d or 10 min × 3/day at a speed of 16 m/min, for 9 days, respectively, dermatitis symptom score, thickness of epidermis/dermis and eosinophil infiltration were decreased in the 2 exercise groups compared to the sedentary living group. The serum levels of IgE, MCP-1 and MDC showed a significant decrease both in the continuous or accumulated exercise groups. Moderate-intensity aerobic exercise ameliorates dermatitis symptoms through immune modulation in the DNCB-treated mouse model for eczema.

Background: Atopic dermatitis (AD) is chronic pruritic inflammatory skin disease in children. Interleukin (IL) 31 is a recently discovered cytokine associated with chronic skin inflammation and pruritus. Objectives: The aims of this study were to determine whether serum IL-31 levels are increased in children with AD and to examine the relationship between IL-31 and other clinical biomarkers in AD. Methods: Serum cytokine levels, including IL-31, IL-4, and IL-12, were measured in 38 patients with AD and 10 healthy children. Peripheral blood eosinophils, serum immunoglobulin E levels, eosinophil cationic protein, and thymic stromal lymphopoietin (TSLP) were measured. We also estimated the clinical severity of AD by using the Scoring Atopic Dermatitis (SCORAD) index by a single clinician. Results: The serum IL-31 levels were significantly higher in the patients with AD than in the healthy children. IL-31 correlated well with the SCORAD index and blood eosinophilic inflammatory markers. The serum level of TSLP was also higher in patients with AD than in the healthy children; however, levels of IL-4 and IL-12 were not different between AD and healthy children. There was no significant difference in serum IL-31 levels between patients with atopic AD and nonatopic AD. Conclusion: This study showed that serum IL-31 levels were significantly elevated in patients with AD than in the healthy children and correlated well with disease severity. IL-31 seemed to be one of the cytokines that induce pruritus and eosinophilic inflammation in AD. Serum IL-31 correlated with pruritic symptoms and disease course of AD.

Background Recent studies have shown that oral administration of probiotics may improve the immune imbalance caused by dysbiosis of the gut microbiome in atopic dermatitis (AD). This study aimed to investigate the clinical and immunological effects of Lactobacillus pentosus in children with mild to moderate AD. Methods Children aged 2–13 years with AD were randomized to receive either 1.0 × 1010 colony-forming units of L. pentosus or placebo, daily, for 12 weeks. The clinical severity of AD and transepidermal water loss were evaluated. Blood eosinophil counts, serum total immunoglobulin E (IgE), and cytokine levels were measured. The diversity and composition of the gut microbiota were also analyzed. Results Eighty-two children were recruited, and 41 were assigned to the probiotics intervention group. The mean scoring of atopic dermatitis (SCORAD) indices at baseline were 30.4 and 34.3 for the probiotics and placebo groups, respectively. At week 12, the mean indices were 23.6 and 23.1 for the probiotics and placebo groups, respectively. Clinical severity decreased significantly over time in both groups, with no significant difference between the two groups. In both groups, there were no significant differences in cytokine levels, microbial diversity, or the relative abundance of the gut microbiota at week 12 compared with the corresponding baseline values. The mean subjective scores of SCORAD indices after intervention for the probiotics group were significantly lower than those for the placebo group in IgE sensitized AD (P = 0.019). Conclusion Our results show improved symptoms in the probiotics and placebo groups, and we could not find additional effects of L. pentosus in AD. However, the mean subjective scores of SCORAD indices for the probiotics group are significantly improved compared with those for the placebo group in allergen-sensitized AD., Graphical Abstract

Background: Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. Aim: We aimed to investigate the relationships between sensitization to mold and lung function parameters in children with asthma. Methods: We reviewed clinical data from 551 children with asthma. They underwent spirometry, methacholine challenge tests, and measurements of blood eosinophils, IgE, ECP and FeNO levels. Skin prick testing (SPT) was performed with 13 common aeroallergens in Korea. Asthmatic children were divided into 3 groups according to their SPT results: Group 1, non-sensitized; Group 2, other allergen-sensitized; and Group 3, mold-sensitized. Results: Among the 551 asthmatic children, 67(15.5%) were sensitized to mold and 366 (84.5%) were sensitized to other aeroallergens. The log mean IgE levels were higher in Groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to Group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO were significantly higher in Groups 2 and 3 but no significant difference was found between the 2 groups. The mean FEV1 was significantly lower in Group 3 (86.9±12.1%pred) than in Groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in Group 3 (0.08±1.91 mg/mL) than in Groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL). Conclusions: We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

PURPOSE Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma. METHODS We retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized). RESULTS Among the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL). CONCLUSIONS We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-γ) also efficiently inhibited tumour growth and prolonged the survival of C57BL/6 mice bearing B16F10 melanoma compared with administration of phosphate-buffered saline (PBS), unmodified S. typhimurium or S. typhimurium expressing empty vector (S. typhimurium [Vec]) in a natural killer (NK) cell-dependent manner. Moreover, genetically modified Salmonella, including S. typhimurium (IFN-γ), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-γ)-mediated tumour suppression was attributed to direct killing of tumour cells rather than to stable anti-tumour immunity. Collectively, these results suggest that tumour-targeted therapy using S. typhimurium (IFN-γ) has potential for melanoma treatment.

Telomerase is a ribonucleoprotein complex the function of which is to add telomeric repeats (TTAGGG)(n) to chromosomal ends, and it is known to play an important role in cellular immortalization. Telomerase is highly active in most tumor cells, yet not in normal cells. As such, it may have possible applications in cancer gene therapy. Telomerase consists of two essential components, telomerase RNA template (hTR) and catalytic subunit (hTERT). hTERT is expressed only in cells and tissues positive for telomerase activity, i.e., tumor and fetal cells. We here tested the possibility of the utilization of the hTERT promoter in targeted cancer gene therapy. We cloned the hTERT promoter in the replace of the CMV promoter and sub-cloned HSV-TK gene to be controlled by hTERT gene promoter in adenovirus shuttle plasmid. Then we constructed recombinant adenovirus Ad-hT-TK, and infected them into normal and human gynecological cancer cell lines. Through these experiments, we identified the selective tumor specific cell death by Ad-hT-TK. Furthermore, FACS analysis and TUNEL assay suggests that the reduced viability is mediated through the induction of apoptosis, indicating that this approach may be a useful method for suppressing cancer growth in targeted cancer gene therapy. These results show that Ad-hT-TK could be used for gynecological cancer gene therapy.

The tumor-suppressing effects of SipB160/HPV16 E7 fusion protein, derived from human papillomavirus, and expressed in Salmonella enterica serovar typhimurium, were evaluated in a cervical cancer model. The expressed E7 protein resulted in efficacious cytotoxicity and tumor growth retardation in TC-1 cervical cancer cells. In addition, in mice bearing TC-1 tumors, live cells of Salmonella expressing HPV16 E7 were administered orally and induced immune responses through interferon-gamma and tumor necrosis factor-alpha cytokine secretion and also suppressed tumor growth (45 %) and prolonged survival (70 %) compared with the control group. These results suggested that the SipB160/HPV16 E7 fusion protein may be a candidate cancer therapeutic agent.

Objective: This article was intended to introduce the Korean Surveillance System for Childhood Asthma (KSSCA) and also to determine the factors that increase the risk for the development of asthma and allergic diseases in preschool children in Korea based on the study results. Methods: The KSSCA pilot study was a web-based, cross-sectional survey that sampled 1002 parents with a biological child aged 2–6 years that visited the website and participated in the survey. This website consisted of a questionnaire designed to measure the history and prevalence of asthma and allergic diseases, the characteristics of dwelling, lifestyle, and the socioeconomic status of the subjects. Using logistic regression analysis, odds ratios (ORs) and 95% confidence intervals (CIs) between each risk factor and disease development were calculated. Results: The rate of a family where a child had asthma was 7.4%, while 34.7% and 35.9% for allergic rhinitis and atopic dermatitis, respectively. The OR (95% CI) that a child whose parents had an allergic disease and was also diagnosed with an allergic disease was 2.86 (2.20–3.72). Children who lived in the first floor or basement of apartments had a higher risk of atopic dermatitis, as well as children from socioeconomically vulnerable families. Upon analysis of allergic reaction tests and disease development, it was found that asthma was associated with the positive reaction of cockroaches and food, allergic rhinitis with mites, and atopic dermatitis with mold and food. Conclusion: The study indicated that genetic and some environmental or socioeconomic factors might be important in the development of asthma and allergic diseases among preschool children in Korea through the web-survey.