Improved Wearable Devices for Dietary Assessment Using a New Camera System.

An unhealthy diet is strongly linked to obesity and numerous chronic diseases. Currently, over two-thirds of American adults are overweight or obese. Although dietary assessment helps people improve nutrition and lifestyle, traditional methods for dietary assessment depend on self-report, which is inaccurate and often biased. In recent years, as electronics, information, and artificial intelligence (AI) technologies advanced rapidly, image-based objective dietary assessment using wearable electronic devices has become a powerful approach. However, research in this field has been focused on the developments of advanced algorithms to process image data. Few reports exist on the study of device hardware for the particular purpose of dietary assessment. In this work, we demonstrate that, with the current hardware design, there is a considerable risk of missing important dietary data owing to the common use of rectangular image screen and fixed camera orientation. We then present two designs of a new camera system to reduce data loss by generating circular images using rectangular image sensor chips. We also present a mechanical design that allows the camera orientation to be adjusted, adapting to differences among device wearers, such as gender, body height, and so on. Finally, we discuss the pros and cons of rectangular versus circular images with respect to information preservation and data processing using AI algorithms.

Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial-mesenchymal transition in esophageal cancer.

The growth of solid tumors requires angiogenesis to provide oxygen and nutrients and to support cell proliferation. The switch from an avascular to a vascular phenotype is typically related to acceleration of tumor growth. Anti-angiogenic therapy is becoming a very promising way for malignant tumors. Meanwhile, malignant tumor cells themselves were able to develop the formation of cell-lined vessels that contribute to tumor neovascularization and supply the nutrients and oxygen, which is called vasculogenic mimicry (VM). However, the molecular mechanism of VM remains unclear. The purpose of this study was to investigate the efficacy of the novel recombinant human endostatin (rh-Endo) protein combined with radiotherapy on human esophageal squamous cell carcinoma (ESCC) cell lines Eca-109 and TE13. Our results showed that rh-Endo combined with radiotherapy significantly inhibited the proliferation, migration, invasion, and VM of human esophageal cancer cells in a dose-dependent manner; however, it has no direct effect on apoptosis of carcinoma cells, which indicated that rh-Endo combined with radiotherapy significantly changed the microenvironment of esophageal carcinoma, and played an important role in preventing distant metastasis. Our findings suggested that rh-Endo inhibited the metastasis of esophageal cancer and the activation of AKT pathway, and the down-regulation of epithelial-mesenchymal transition (EMT) may be associated with such effect of rh-Endo. These results also supported the bright prospect of rh-Endo combined with radiotherapy for clinical applications in the future.

CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma.

Background: The function of Chromobox 4 (CBX4) function has attracted attention in many cancer types due to its unique biological role; however, its mechanism in esophageal squamous cell carcinoma (ESCC) under radiotherapeutic treatment has not yet been investigated. Methods: Silencing of CBX4 was carried out in TE-13 and KYSE-150 cell lines. Cell proliferation, radiosensitivity, DNA damage, apoptosis, and cell cycle distribution were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, immunofluorescence, flow cytometry, and immunoblot in vitro. In vivo xenograft models were also used to assess tumor cell growth and radioresistance. The underpinning mechanisms were explored based on pathway analysis and confirmed by rescue experiments, detecting cellular autophagy. Results: Knockdown of CBX4 resulted in reduced tumor growth and enhanced radio-response in vivo and in vitro. Down-regulating CBX4 increased DNA damage, apoptotic rate, and G2/M arrest induced by radiation in ESCC cell lines. Gene Set Enrichment Analysis (GSEA) revealed that CBX4 was associated with cellular autophagy regulation. Enhanced radiosensitivity in ESCC cells silenced for CBX4 was partially blocked by autophagy inhibition (P<0.05). Beclin 1 was upregulated at the gene and protein levels in ESCC cells with CBX4 knockdown after irradiation, and overexpressing Beclin 1 reversed the radiosensitivity of ESCC cells with CBX4 knockdown (P<0.05). Conclusions: By regulating autophagic activity, CBX4 contributes to radioresistance. Targeting CBX4 might constitute an efficient approach for increasing radiosensitivity in ESCC.

Food/Non-Food Classification of Real-Life Egocentric Images in Low- and Middle-Income Countries Based on Image Tagging Features.

Malnutrition, including both undernutrition and obesity, is a significant problem in low- and middle-income countries (LMICs). In order to study malnutrition and develop effective intervention strategies, it is crucial to evaluate nutritional status in LMICs at the individual, household, and community levels. In a multinational research project supported by the Bill & Melinda Gates Foundation, we have been using a wearable technology to conduct objective dietary assessment in sub-Saharan Africa. Our assessment includes multiple diet-related activities in urban and rural families, including food sources (e.g., shopping, harvesting, and gathering), preservation/storage, preparation, cooking, and consumption (e.g., portion size and nutrition analysis). Our wearable device ("eButton" worn on the chest) acquires real-life images automatically during wake hours at preset time intervals. The recorded images, in amounts of tens of thousands per day, are post-processed to obtain the information of interest. Although we expect future Artificial Intelligence (AI) technology to extract the information automatically, at present we utilize AI to separate the acquired images into two binary classes: images with (Class 1) and without (Class 0) edible items. As a result, researchers need only to study Class-1 images, reducing their workload significantly. In this paper, we present a composite machine learning method to perform this classification, meeting the specific challenges of high complexity and diversity in the real-world LMIC data. Our method consists of a deep neural network (DNN) and a shallow learning network (SLN) connected by a novel probabilistic network interface layer. After presenting the details of our method, an image dataset acquired from Ghana is utilized to train and evaluate the machine learning system. Our comparative experiment indicates that the new composite method performs better than the conventional deep learning method assessed by integrated measures of sensitivity, specificity, and burden index, as indicated by the Receiver Operating Characteristic (ROC) curve.

Liriodenine enhances radiosensitivity in esophageal cancer ECA-109 cells by inducing apoptosis and G2/M arrest.

At present, chemotherapy and radiotherapy represent the primary modalities of treatment for patients with unresectable esophageal squamous cell carcinoma (ESCC). However, the outcome of patients remains poor owing to radioresistance. The present study aimed to determine the radiosensitizing effect of liriodenine, an aporphine alkaloid derived from Enicosanthellum pulchrum, and investigating the underlying mechanisms in ESCC, using the esophageal cancer ECA-109 cell line. Cellular proliferation was evaluated using the Cell Counting kit-8 assay. Colony formation assay was performed to characterize the radiosensitive effects of liriodenine on ECA-109 cells, and flow cytometry was used to detect the percentage of cells undergoing apoptosis. An immunofluorescence assay was utilized to evaluate the DNA damage repair ability. Western blotting was used to assess the protein levels of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax). Liriodenine dose-dependently inhibited ECA-109 cell viability. The clonogenic survival assay demonstrated that liriodenine increased the radiosensitivity of ESCC cells, with a sensitization enhancement ratio of 1.11-1.69. The results of flow cytometry demonstrated that liriodenine induced apoptosis and G2/M arrest. The immunofluorescence assay revealed that liriodenine delays DNA damage repair. The upregulation of Bax and Caspase-3, and the suppression of Bcl-2 confirmed that apoptosis was occurring. Liriodenine radiosensitizes ECA-109 cells by inducing apoptosis and G2/M arrest. The findings of the present study indicated that liriodenine may represent an anticancer agent with promising potential for the treatment of ESCC.

AQP4­knockout alleviates the lipopolysaccharide­induced inflammatory response in astrocytes via SPHK1/MAPK/AKT signaling.

To date, aquaporin­4 (AQP4) has been considered as a critical contributor to neuroinflammation, but little is known about the underlying mechanism. Previous studies have shown that a critical enzyme involved in the sphingomyelin cycle, sphingosine kinase 1 (SPHK1), is implicated in inflammatory processes and contributes to chronic neuroinflammation. The present study investigated the role of AQP4 in proinflammatory cytokine release from astrocytes, with an emphasis on the SPHK1/mitogen­activated protein kinase (MAPK)/protein kinase B (AKT) pathway. Using primary cultures isolated from AQP4+/+ and AQP4­/­ embryos, the production of tumor necrosis factor­α (TNF­α)/interleukin­6 (IL­6) from astrocytes challenged by lipopolysaccharide (LPS) was compared. The results showed increased secretion of TNF­α/IL­6 in the two groups following LPS treatment, but a significantly lower level was observed in the AQP4­/­ group compared with that in the AQP4+/+ group. Although upregulation of SPHK1 was detected in the two genotypes, only a mild increase in SPHK1 was found in the AQP4­/­ genotype. The phosphorylation of MAPK/AKT was also confirmed to be attenuated in the AQP4­/­ group, suggesting decreased MAPK/AKT signaling over time in AQP4­/­ astrocytes. Overall, the study findings demonstrated that AQP4 deficiency alleviates proinflammatory cytokine release from astrocytes, in association with the SPHK1/MAPK/AKT pathway. This data improves our understanding of AQP4 in neuroinflammatory events, highlighting a novel profile of SPHK1 as a potential target for the treatment of CNS inflammation.

Exosomes Derived from Irradiated Esophageal Carcinoma-Infiltrating T Cells Promote Metastasis by Inducing the Epithelial-Mesenchymal Transition in Esophageal Cancer Cells.

Exosomes are nanovesicles derived from tumor and normal cells that are detectable in human biological fluids, such as plasma, and cell culture supernatants. The function of exosome secretion from "normal" cells is unclear. Although numerous studies have investigated exosomes derived from hematopoietic cells, little is known regarding exosomes fromT cells, even though these cells play significant roles in innate and acquired immunity. A CCK-8 assay was used to examine the ability of exosomes to inhibit TE13 cell proliferation. In vitro invasion and wound healing assays were conducted to explore the effects of exosomes on TE13 cell migration and invasion. A Western blottinganalys is was performed to investigate the effects of exosomes on the expression of the EMT-related moleculesß-catenin, NF-κB and snail. This study aimed to investigate the effects of exosomes from irradiated T cells on the human esophageal squamous cell carcinoma (ESCC) cell line TE13 and revealed that exosomes inhibit the proliferation but promote the metastasis of TE13 cells in a dose-and time-dependent manner. Furthermore, exosomes significantly increased the expression of ß-catenin, NF-κB and snail in TE13 cells. The results of this study suggest an important role for T cell-derived exosomes in the progression of esophageal carcinoma: T cell-derived exosomes promote esophageal cancer metastasis, likely by promoting the EMT through the upregulation of ß-catenin and the NF-κB/snail pathway. Moreover, this study supports the use of exosomes as a nearly perfect example of biomimetic nanovesicles that could be utilized in future therapeutic strategies against various diseases, including cancer.

Nutlin-3, an Antagonist of MDM2, Enhances the Radiosensitivity of Esophageal Squamous Cancer with Wild-Type p53.

Murine double minute 2 (MDM2) negatively regulates the activity of the p53 protein and plays a vital role in cell cycle arrest, apoptosis, and senescence mediated by p53. Nutlin-3, an antagonist of MDM2, is frequently used in anti-cancer studies. In many human tumors, nutlin-3 stabilizes p53 status and enhances p53 expression in cells with wild-type p53. However, the effect of nutlin-3 combined with radiotherapy on esophageal squamous cancer (ESCC) has not been reported. In this study, we examined whether nutlin-3 increases the radiosensitivity of ESCC in vitro and in vivo.We chose two cell lines, ECA-109 (wild-type p53) and TE-13 (p53 mutated), for the following experiments. Cell proliferation and clonogenic survival experiments showed that nutlin-3 inhibits the cell growth and colony formation of ECA-109 cells in a dose-dependent manner. Flow cytometry analysis showed that the apoptosis rate of ECA-109 cells co-treated with nutlin-3 and irradiation(IR) was significantly increased compared with cells treated with irradiation or nutlin-3 alone. Western blotting detected the expression of apoptosis-associated proteins in ECA-109 cells in response to nutlin-3 and irradiation. These effects were not evident in TE-13 cells. Xenograft mouse models indicated that nutlin-3 suppresses tumor growth and promotes radiosensitivity in the ESCC cell line ECA-109 in vivo. We have demonstrated that co-treatment of nutlin-3 with irradiation can significantly inhibit the growth and improve the radiosensitivity of ESCC cells with wild-type p53. The study suggests that nutlin-3 may be a potent therapeutic agent in conjunction with radiotherapy in ESCC.

The mechanisms of radioresistance in esophageal squamous cell carcinoma and current strategies in radiosensitivity.

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death worldwide. Surgery is the primary form of treatment, but the survival is poor, especially for patients with locally advanced esophageal cancer. Radiotherapy has been a critical treatment option that may be combined with chemotherapy in patients with unresectable esophageal cancer. However, resistance to chemoradiotherapy might result in treatment failures and cancer relapse. This review will mainly focus on the possible cellular mechanisms and tumor-associated microenvironmental (TAM) factors that result in radioresistance in patients with esophageal cancer. In addition, current strategies to increase radiosensitivity, including targeted therapy and the use of radiosensitive biomarkers in clinical treatment, are discussed in this review.

eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice. RESULTS: eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues (P<0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls (P<0.05), while silencing eEF2K reduced cell proliferation (P<0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates (P<0.05), while higher levels of eEF2K expression with faster migration and invasion rates (P<0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo (P<0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone (P<0.05). CONCLUSION: eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.

Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met.

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.

Orchestration of the crosstalk between astrocytes and cancer cells affects the treatment and prognosis of lung cancer sufferers with brain metastasis.

Brain metastasis is an inauspicious consequence of lung cancer. However, the majority of cancer cells that seep into the brain died of unknown causes, only a few survived and developed into metastatic brain tumor. Communication between cancer cells and host tissue is viewed as an essential event during metastasis, but little is known about the accurate control of this processes. Within the lesion of brain metastasis, abundant activated astrocytes are observed with lung cancer cells. Previous studies have demonstrated that the astrocyte network served a protective role in the central nervous system (CNS) and most malignant cells that seep into the brain perish were rejected by astrocytes. Reactive astrocytes generated protease plasmin and cytotoxic cytokines as a defense against metastatic invasion. But recently, other investigators argued that tumor cells interactions with astrocytes promote the progression of brain metastases and protect them from the cytotoxic effects of chemotherapy. In this article, we review the architecture between astrocytes and infiltrated cancer cells, and raise a future perspective on therapeutic potential of targeting crosstalk modulators against brain metastasis.