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.

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.

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.

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.

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).

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.

Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 and the FOXOs Pathway.

It has been suggested that age-related neurodegeneration might be associated with neuropeptide Y (NPY); sirtuin1 (SIRT1) and forkhead box transcription factors O subfamily (FOXOs) pathways. Melatonin, a hormone mainly secreted by the pineal gland, is another anti-aging agent associated with the SIRT1-FOXOs pathway. This study aimed to compare the effects of melatonin (Mel) and caloric restriction (CR) on the expression of Sirt1, FoxO1, FoxO3a and FOXOs target genes in the aging mouse hippocampus. Neuropeptide Y-knockout (NpyKO) and wild-type (WT) male mice aged 19 months were previously treated either with food ad libitum or CR for 16 months. WT old animals were divided into four groups: control, CR, Mel and CR+Mel treated groups. The Mel and CR+Mel were treated with melatonin 10 mg/kg, daily, subcutaneously for 7 consecutive days. Mel treatment upregulated the mRNA expression of Sirt1, FOXOs (FoxO1 and FoxO3a) target genes that regulated the cell cycle [e.g., cyclin-dependent kinase inhibitor 1B (p27)], Wingless and INT-1 (Wnt1) and inducible signaling pathway protein 1 (Wisp1) in the aged mouse hippocampus. CR treatment also showed the similar actions. However, the mRNA expression of Sirt1, FoxO1, FoxO3a, p27 or Wisp1 did not alter in the CR+Mel group when compared with CR or Mel group. Melatonin could not produce any additive effect on the CR treatment group, suggesting that both treatments mimicked the effect, possibly via the same pathway. NPY which mediates physiological adaptations to energy deficits is an essential link between CR and longevity in mice. In order to focus on the role of Npy in mediating the effects of melatonin, the gene expression between NpyKO and WT male mice were compared. Our data showed that, in the absence of Npy, melatonin could not mediate effects on those gene expressions, suggesting that Npy was required for melatonin to mediate the effect, possibly, on life extension.

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).

Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

Modification of ghrelin receptor signaling by somatostatin receptor-5 regulates insulin release.

Both ghrelin and somatostatin (SST) inhibit glucose-stimulated insulin secretion (GSIS) from pancreatic ß-cells, but how these independent actions are regulated has been unclear. The mechanism must accommodate noncanonical ghrelin receptor (GHS-R1a)-G-protein coupling to Gα(i/o) instead of Gα(q11) and dependence on energy balance. Here we present evidence for an equilibrium model of receptor heteromerization that fulfills these criteria. We show that GHS-R1a coupling to Gα(i/o) rather than Gα(q11) requires interactions between GHS-R1a and SST receptor subtype 5 (SST5) and that in the absence of SST5 ghrelin enhances GSIS. At concentrations of GHS-R1a and SST5 expressed in islets, time-resolved FRET and bioluminescence resonance energy transfer assays illustrate constitutive formation of GHS-R1a:SST5 heteromers in which ghrelin, but not SST, suppresses GSIS and cAMP accumulation. GHS-R1a-G-protein coupling and the formation of GHS-R1a:SST5 heteromers is dependent on the ratio of ghrelin to SST. A high ratio enhances heteromer formation and Gα(i/o) coupling, whereas a low ratio destabilizes heteromer conformation, restoring GHS-R1a-Gα(q11) coupling. The [ghrelin]/[SST] ratio is dependent on energy balance: Ghrelin levels peak during acute fasting, whereas postprandially ghrelin is at a nadir, and islet SST concentrations increase. Hence, under conditions of low energy balance our model predicts that endogenous ghrelin rather than SST establishes inhibitory tone on the ß-cell. Collectively, our data are consistent with physiologically relevant GHS-R1a:SST5 heteromerization that explains differential regulation of islet function by ghrelin and SST. These findings reinforce the concept that signaling by the G-protein receptor is dynamic and dependent on protomer interactions and physiological context.

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.

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.

Regulatory role of Echinochrome A in cancer-associated fibroblast-mediated lung cancer cell migration.

Echinochrome A (Ech A), a marine biosubstance isolated from sea urchins, is a strong antioxidant, and its clinical form, histochrome, is being used to treat several diseases, such as ophthalmic, cardiovascular, and metabolic diseases. Cancer-associated fibroblasts (CAFs) are a component of the tumor stroma and induce phenotypes related to tumor malignancy, including epithelial-mesenchymal transition (EMT) and cancer stemness, through reciprocal interactions with cancer cells. Here, we investigated whether Ech A modulates the properties of CAFs and alleviates CAF-induced lung cancer cell migration. First, we observed that the expression levels of CAF markers, Vimentin and fibroblast-activating protein (FAP), were decreased in Ech A-treated CAF-like MRC5 cells. The mRNA transcriptome analysis revealed that in MRC5 cells, the expression of genes associated with cell migration was largely modulated after Ech A treatment. In particular, the expression and secretion of cytokine and chemokine, such as IL6 and CCL2, stimulating cancer cell metastasis was reduced through the inactivation of STAT3 and Akt in MRC5 cells treated with Ech A compared to untreated MRC5 cells. Moreover, while conditioned medium from MRC5 cells enhanced the migration of non-small cell lung cancer cells, conditioned medium from MRC5 cells treated with Ech A suppressed cancer cell migration. In conclusion, we suggest that Ech A might be a potent adjuvant that increases the efficacy of cancer treatments to mitigate lung cancer progression.

Histone demethylase JMJD2B-mediated cell proliferation regulated by hypoxia and radiation in gastric cancer cell.

Histone modifying factors are functional components of chromatin and play a role in gene regulation. The expression level of JMJD2B, a histone demethylase, is notably up-regulated in cancer tissues. Upregulation of JMJD2B promotes cancer cell proliferation under hypoxic conditions through target gene expression. Here, we describe the patterns of histone methylation and JMJD2B expression under various stressed conditions, such as hypoxia and radiation, in a gastric cancer cell line. JMJD2B expression in AGS cells was actively regulated by hypoxia and radiation. Chromatin immunoprecipitation experiments demonstrated that binding of JMJD2B on the cyclin A1 (CCNA1) promoter resulted in CCNA1 upregulation under hypoxic conditions. Furthermore, we confirmed that AGS cell proliferation was directly affected by JMJD2B and CCNA1 expression by performing experiments with JMJD2B depleted cells. Interestingly, the effects of JMJD2B on cell growth under hypoxia were remarkably repressed after gamma-ray irradiation. These results suggest that JMJD2B may play a central role in gastric cancer cell growth and might constitute a novel therapeutic target to overcome hypoxia-induced radio-resistance, thereby improving the efficiency of radiation therapy.

The histone demethylase JMJD1A regulates adrenomedullin-mediated cell proliferation in hepatocellular carcinoma under hypoxia.

We studied the roles of JMJD1A and its target gene ADM in the growth of hepatocellular carcinomas (HCCs) and breast cancer cells under hypoxic conditions. Hypoxia stimulated HepG2 and Hep3B cell proliferation but had no effect on MDA-MB-231 cell proliferation. Interestingly, the JMJD1A and ADM expressions were enhanced by hypoxia only in HepG2 and Hep3B cells. Our ChIP results showed that hypoxia-induced HepG2 and Hep3B cell proliferation is mediated by JMJD1A upregulation and subsequent decrease in methylation in the ADM promoter region. Furthermore, JMJD1A gene silencing abrogated the hypoxia-induced ADM expression and inhibited HepG2 and Hep3B cell growth. These data suggest that JMJD1A might function as a proliferation regulator in some cancer cell types.

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.

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.