AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

Influence of Adipokines on Metabolic Dysfunction and Aging.

Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic abnormalities, such as hypertension, hyperglycemia, and dyslipidemia, collectively termed metabolic syndrome. In particular, visceral fat accretion is considered as a hallmark of aging and is strongly linked to higher mortality rates in humans. Adipokines, bioactive peptides secreted by adipose tissue, play crucial roles in regulating appetite, satiety, adiposity, and metabolic balance, thereby rendering them key players in alleviating metabolic diseases and potentially extending health span. In this review, we elucidated the role of adipokines in the development of obesity and related metabolic disorders while also exploring the potential of certain adipokines as candidates for longevity interventions.

Breast cancer malignancy is governed by regulation of the macroH2A2/TM4SF1 axis, the AKT/NF-κB pathway, and elevated MMP13 expression.

The histone variant, macroH2A (mH2A) influences gene expression through epigenetic regulation. Tumor suppressive function of mH2A isoforms has been reported in various cancer types, but few studies have investigated the functional role of mH2A2 in breast cancer pathophysiology. This study aimed to determine the significance of mH2A2 in breast cancer development and progression by exploring its downstream regulatory mechanisms. Knockdown of mH2A2 facilitated the migration and invasion of breast cancer cells, whereas its overexpression exhibited the opposite effect. In vivo experiments revealed that augmenting mH2A2 expression reduced tumor growth and lung metastasis. Microarray analysis showed that TM4SF1 emerged as a likely target linked to mH2A2 owing to its significant suppression in breast cancer cell lines where mH2A2 was overexpressed among the genes that exhibited over twofold upregulation upon mH2A2 knockdown. Suppressing TM4SF1 reduced the migration, invasion, tumor growth, and metastasis of breast cancer cells in vitro and in vivo. TM4SF1 depletion reversed the increased aggressiveness triggered by mH2A2 knockdown, suggesting a close interplay between mH2A2 and TM4SF1. Our findings also highlight the role of the mH2A2/TM4SF1 axis in activating the AKT/NF-κB pathway. Consequently, activated NF-κB signaling leads to increased expression and secretion of MMP13, a potent promoter of metastasis. In summary, we propose that the orchestrated regulation of the mH2A2/TM4SF1 axis in conjunction with the AKT/NF-κB pathway and the subsequent elevation in MMP13 expression constitute pivotal factors governing the malignancy of breast cancer.

Downregulation of complement factor H attenuates the stemness of MDA­MB­231 breast cancer cells via modulation of the ERK and p38 signaling pathways.

The complement system is a powerful innate immune system deployed in the immediate response to pathogens and cancer cells. Complement factor H (CFH), one of the regulators involved in the complement cascade, can interrupt the death of target cells. Certain types of cancer, such as breast cancer, can adopt an aggressive phenotype, such as breast cancer stem cells (BCSCs), through enhancement of the defense system against complement attack by amplifying various complement regulators. However, little is known about the association between CFH and BCSCs. In the present study, the roles of CFH in the CSC characteristics and radioresistance of MDA-MB-231 human breast cancer cells were investigated. CFH knockdown in MDA-MB-231 cells decreased the viability of the cells upon complement cascade activation. Notably, CFH knockdown also decreased cell survival and suppressed mammosphere formation, cell migration and cell invasion by attenuating radioresistance. Additionally, CFH knockdown further enhanced irradiation-induced apoptosis through G2/M cell cycle arrest. It was also discovered that CFH knockdown attenuated the aggressive phenotypes of cancer cells by regulating CSC-associated gene expression. Finally, by microarray analysis, it was found that the expression of erythrocyte membrane protein band 4.1-like 3 (EPB41L3) was markedly increased following CFH knockdown. EPB41L3 inhibited ERK and activated the p38 MAPK signaling pathway. Taken together, these results indicated that CFH knockdown attenuated CSC properties and radioresistance in human breast cancer cells via controlling MAPK signaling and through upregulation of the tumor suppressor, EPB41L3.

Reducing cost in DNA-based data storage by sequence analysis-aided soft information decoding of variable-length reads.

MOTIVATION: DNA-based data storage is one of the most attractive research areas for future archival storage. However, it faces the problems of high writing and reading costs for practical use. There have been many efforts to resolve this problem, but existing schemes are not fully suitable for DNA-based data storage, and more cost reduction is needed. RESULTS: We propose whole encoding and decoding procedures for DNA storage. The encoding procedure consists of a carefully designed single low-density parity-check code as an inter-oligo code, which corrects errors and dropouts efficiently. We apply new clustering and alignment methods that operate on variable-length reads to aid the decoding performance. We use edit distance and quality scores during the sequence analysis-aided decoding procedure, which can discard abnormal reads and utilize high-quality soft information. We store 548.83 KB of an image file in DNA oligos and achieve a writing cost reduction of 7.46% and a significant reading cost reduction of 26.57% and 19.41% compared with the two previous works. AVAILABILITY AND IMPLEMENTATION: Data and codes for all the algorithms proposed in this study are available at: https://github.com/sjpark0905/DNA-LDPC-codes.

G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer.

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-ß superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.

The Role of Neuropeptide Y in Adipocyte-Macrophage Crosstalk during High Fat Diet-Induced Adipose Inflammation and Liver Steatosis.

Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY-/- mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD.

Quantitative determination of spin-orbit-induced magnetic field in GaMnAs by field-scan planar Hall measurements.

Spin-orbit-induced (SOI) effective magnetic field in GaMnAs film with in-plane magnetic anisotropy has been investigated by planar Hall effect measurements. The presence of SOI field was identified by a shift between planar Hall resistance (PHR) hystereses observed with positive and negative currents. The difference of switching fields occurring between the two current polarities, which is determined by the strength of the SOI field, is shown to depend on the external field direction. In this paper we have developed a method for obtaining the magnitude of the SOI fields based on magnetic free energy that includes the effects of magnetic anisotropy and the SOI field. Using this approach, the SOI field for a given current density was accurately obtained by fitting to the observed dependence of the switching fields on the applied field directions. Values of the SOI field obtained with field scan PHR measurements give results that are consistent with those obtained by analyzing the angular dependence of PHR, indicating the reliability of the field scan PHR method for quantifying the SOI-field in GaMnAs films. The magnitude of the SOI field systematically increases with increasing current density, demonstrating the usefulness of SOI fields for manipulation of magnetization by current in GaMnAs films.

Cooperative sequence clustering and decoding for DNA storage system with fountain codes.

MOTIVATION: In DNA storage systems, there are tradeoffs between writing and reading costs. Increasing the code rate of error-correcting codes may save writing cost, but it will need more sequence reads for data retrieval. There is potentially a way to improve sequencing and decoding processes in such a way that the reading cost induced by this tradeoff is reduced without increasing the writing cost. In past researches, clustering, alignment and decoding processes were considered as separate stages but we believe that using the information from all these processes together may improve decoding performance. Actual experiments of DNA synthesis and sequencing should be performed because simulations cannot be relied on to cover all error possibilities in practical circumstances. RESULTS: For DNA storage systems using fountain code and Reed-Solomon (RS) code, we introduce several techniques to improve the decoding performance. We designed the decoding process focusing on the cooperation of key components: Hamming-distance based clustering, discarding of abnormal sequence reads, RS error correction as well as detection and quality score-based ordering of sequences. We synthesized 513.6 KB data into DNA oligo pools and sequenced this data successfully with Illumina MiSeq instrument. Compared to Erlich's research, the proposed decoding method additionally incorporates sequence reads with minor errors which had been discarded before, and thus was able to make use of 10.6-11.9% more sequence reads from the same sequencing environment, this resulted in 6.5-8.9% reduction in the reading cost. Channel characteristics including sequence coverage and read-length distributions are provided as well. AVAILABILITY AND IMPLEMENTATION: The raw data files and the source codes of our experiments are available at: https://github.com/jhjeong0702/dna-storage.

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer.

Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule's efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer.

Devising a Distributed Co-Simulator for a Multi-UAV Network.

Practical evaluation of the Unmanned Aerial Vehicle (UAV) network requires a lot of money to build experiment environments, which includes UAVs, network devices, flight controllers, and so on. To investigate the time-sensitivity of the multi-UAV network, the influence of the UAVs' mobility should be precisely evaluated in the long term. Although there are some simulators for UAVs' physical flight, there is no explicit scheme for simulating both the network environment and the flight environments simultaneously. In this paper, we propose a novel co-simulation scheme for the multiple UAVs network, which performs the flight simulation and the network simulation simultaneously. By considering the dependency between the flight status and networking situations of UAV, our work focuses on the consistency of simulation state through synchronization among simulation components. Furthermore, we extend our simulator to perform multiple scenarios by exploiting distributed manner. We verify our system with respect to the robustness of time management and propose some use cases which can be solely simulated by this.

Transhiatal esophagogastric anastomosis and postoperative monitoring of thoracic esophageal leiomyosarcoma in a dog.

A 12-year-old Maltese dog was referred to the Veterinary Teaching Hospital at Konkuk University because of severe regurgitation. Radiography, ultrasonography, and computed tomography showed a mass in the thoracic esophagus. Localization of the tumor, its extraluminal nature, the positioning and involvement of the stomach, and the lack of diffuse metastasis to the lung were factors considered when developing a surgical plan. A successful surgical procedure was performed. The final diagnosis was leiomyosarcoma. Following surgery, clinical signs were significantly reduced and postoperative complications were not observed. The dog died 25 days after surgery; we suspected that the death was due to postoperative stricture. Key clinical message: Surgical approaches that prioritize maintenance of low tension on the thoracic esophagus are important to prevent arrhythmia, bradycardia, and ventricular premature complex during esophagogastric anastomosis. In dogs with a small esophageal lumen anastomosis may lead to postoperative stricture.

Anastomose oesophago-gastrique trans-hiatal et suivi post-opératoire d'un léiomyosarcome oesophagien thoracique chez un chien. Un Bichon maltais âgé de 12 ans fut référé à l'hôpital vétérinaire d'enseignement de la Konkuk University à cause de régurgitations sévères. Les radiographies, l'échographie et la tomodensitométrie ont montré la présence d'une masse dans l'oesophage thoracique. La localisation de la tumeur, sa nature extra-luminaire, le positionnement et l'implication de l'estomac et l'absence de métastase diffuse au poumon étaient des facteurs considérés lors du développement d'un plan chirurgical. Une procédure chirurgicale réussie fut réalisée. Le diagnostic final était un léiomyosarcome. Suite à la chirurgie, les signes cliniques étaient significativement réduits et aucune complication post-opératoire ne fut observée. Le chien est décédé 25 jours après la chirurgie, nous soupçonnons que la mort était due à un rétrécissement post-opératoire.Message clinique clé:Les approches chirurgicales qui priorisent le maintien de faible tension sur l'oesophage thoracique sont importantes pour prévenir l'arythmie, la bradycardie et un complexe ventriculaire prématuré lors d'une une anastomose oesophagogastrique. Chez les chiens avec un petit lumen oesophagien l'anastomose peut entraîner un rétrécissement post-opératoire.(Traduit par Dr Serge Messier).

NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning.

The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice.

AIM: Caloric restriction (CR), which limits the caloric intake to 60-70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. METHODS: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. RESULTS: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. CONCLUSIONS: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••-••.

UAV Flight and Landing Guidance System for Emergency Situations †.

Unmanned aerial vehicles (UAVs) with high mobility can perform various roles such as delivering goods, collecting information, recording videos and more. However, there are many elements in the city that disturb the flight of the UAVs, such as various obstacles and urban canyons which can cause a multi-path effect of GPS signals, which degrades the accuracy of GPS-based localization. In order to empower the safety of the UAVs flying in urban areas, UAVs should be guided to a safe area even in a GPS-denied or network-disconnected environment. Also, UAVs must be able to avoid obstacles while landing in an urban area. For this purpose, we present the UAV detour system for operating UAV in an urban area. The UAV detour system includes a highly reliable laser guidance system to guide the UAVs to a point where they can land, and optical flow magnitude map to avoid obstacles for a safe landing.

Association of Sarcopenia with Metabolic Syndrome in Korean Population Using 2009-2010 Korea National Health and Nutrition Examination Survey.

Background: Some studies have investigated the relationship between sarcopenia and metabolic syndrome, and they have focused mainly on older subjects. Therefore, we assessed the association between sarcopenia and metabolic syndrome in South Korean adults 20 years of age or older using data from the 2009-2010 Korean National Health and Nutrition Examination Survey (KNHANES). Methods: This study involved 12,256 (5350 males and 6906 females) participants from the 2009-2010 KNHANES 20 years of age or older. Appendicular skeletal muscle mass (ASM) was measured by dual X-ray absorptiometry. Sarcopenia index (SI) was calculated as ASM/body mass index and sarcopenia was defined as an SI of <0.789 in males and <0.521 in females. Metabolic syndrome was defined by the presence of at least three of the following abnormalities: abdominal obesity, high blood pressure, high blood glucose level, high triglyceride level, and low high-density lipoprotein cholesterol level. Results: After adjustment for covariates, the association between sarcopenia and metabolic syndrome was significant (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.74-2.45). In addition, when stratified by age groups, the significant associations between sarcopenia and metabolic syndrome remained in all age groups (20-39 years: OR 2.13, 95% CI 1.08-4.19; 40-64 years: OR 2.13, 95% CI 1.68-2.71; ≥65 years: OR 1.98, 95% CI 1.54-2.54). Conclusion: The association between sarcopenia and metabolic syndrome was significant in South Korean adults. Moreover, the significant associations were present in every age group evaluated.

Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction.

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly depending on nutritional states.

Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds.

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (miR-139-5p, miR-142-3p, miR-142-5p, and miR-223) and show that miR-223 is critical for infection control. miR-223Y/- mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of Staphylococcus aureus-infected wounds. We also showed that the expression of miR-223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/--derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus-infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.

Devising Mobile Sensing and Actuation Infrastructure with Drones.

Vast applications and services have been enabled as the number of mobile or sensing devices with communication capabilities has grown. However, managing the devices, integrating networks or combining services across different networks has become a new problem since each network is not directly connected via back-end core networks or servers. The issue is and has been discussed especially in wireless sensor and actuator networks (WSAN). In such systems, sensors and actuators are tightly coupled, so when an independent WSAN needs to collaborate with other networks, it is difficult to adequately combine them into an integrated infrastructure. In this paper, we propose drone-as-a-gateway (DaaG), which uses drones as mobile gateways to interconnect isolated networks or combine independent services. Our system contains features that focus on the service being provided in the order of importance, different from an adaptive simple mobile sink system or delay-tolerant system. Our simulation results have shown that the proposed system is able to activate actuators in the order of importance of the service, which uses separate sensors' data, and it consumes almost the same time in comparison with other path-planning algorithms. Moreover, we have implemented DaaG and presented results in a field test to show that it can enable large-scale on-demand deployment of sensing and actuation infrastructure or the Internet of Things (IoT).

EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells.

Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC. We selected CD44 and EpCAM peptides that bind to HLA-A2 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Our data showed that CSCs express high levels of tumor-associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Pulsing DCs with CD44 and EpCAM peptides resulted in the efficient generation of mature DCs (mDCs), thus enhancing T cell stimulation and generating potent cytotoxic T lymphocytes (CTLs). The activation of CSC peptide-specific immune responses by the DC vaccine in combination with standard chemotherapy may provide better clinical outcomes in advanced carcinomas.