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At least 1,261 records · Page 70

The Doomsday Equation and 50 years beyond: new perspectives on the human‐water system

In 1960, von Foerster et al. humorously predicted an abrupt transition in human population growth to occur in the mid‐21st century. Their so‐called ‘Doomsday’ emerged from either progressive degradation of a finite resource or faster‐than‐exponential growth of an increasingly resource‐use efficient population, though what constitutes this resource was not made explicit. At present, few dispute the claim that water is the most fundamental resource to sustainable human population growth. Multiple lines of evidence demonstrate that the global water system exhibits nontrivial dynamics linked to similar patterns in population growth. Projections of the global water system range from a finite carrying capacity regulated by accessible freshwater, or ‘peak renewable water,’ to punctuated evolution with new supplies and improved efficiency gained from technological and social innovation. These projections can be captured, to first order, by a single delay differential equation with human–water interactions parameterized as a delay kernel that links present water supply to the population history and its impacts on water resources. This kernel is a macroscopic representation of social, environmental, and technological factors operating in the human‐water system; however, the mathematical form remains unconstrained by available data. A related model of log‐periodic, power‐law growth confirms that global water use evolves through repeated periods of rapid growth and stagnation, a pattern remarkably consistent with historical anecdotes. Together, these models suggest a possible regime shift leading to a new phase of water innovation in the mid‐21st century that arises from delayed feedback between population growth and development of water resources. WIREs Water 2015, 2:407–414. doi: 10.1002/wat2.1080 This article is categorized under: Engineering Water > Planning Water

Parolari, Anthony J.↗

A Real-Time Big Data Control-Theoretical Framework for Cyber-Physical-Human Systems [Book Chapter]

It is known that cyber-physical-human systems naturally arise from interdependent infrastructure systems and smart connected communities. Such applications require ubiquitous information sensing and processing, intelligent machine-to-machine communication for a seamless coordination, as well as intelligent interactions between humans and machines. This chapter presents a control-theoretical framework to model heterogeneous physical dynamic systems, information and communication, as well as cooperative controls and/or distributed optimization of such interconnected systems. It is shown that efficient analytical and computational algorithms can be modularly designed and hierarchically implemented to operate and optimize cyber-physical-human systems, first to quantify individually the input–output relationship of nonlinear dynamic behaviors of every physical subsystem, then to coordinate locally both cyber-physical interactions of neighboring agents as well as physical-human interactions, and finally to dynamically model and optimize the overall networked system. The hierarchical structure makes the overall optimization and control problem scalable and solvable. Moreover, the three levels integrate individual designs and optimization, distributed cooperative optimization, and decision-making through real-time, data-driven, model-based learning and control. Specifically, one of the contributions of the chapter is to demonstrate how the combination of dissipativity theory and cooperative control serves as a natural framework and promising tools to analyze, optimize, and control such large-scale system. Application to digital grid is investigated as an illustrative example.

97 MATHEMATICS AND COMPUTING↗

Four Perspectives on Human Bias in Visual Analytics

Mixed-initiative visual analytic systems steer analytical models and adapt views by making inferences from users' behavioral patterns with the system. Because such systems rely on incorporating implicit and explicit user feedback, they are particularly susceptible to the injection and propagation of human biases. To ultimately guard against the potentially negative effects of systems biased by human users, we must first qualify what we mean by the term bias. Thus, in this paper we describe four different perspectives on human bias that are particularly relevant to visual analytics. We discuss the interplay of human and computer system biases, particularly their roles in mixed-initiative systems. Given that the term bias is used to describe several different concepts, our goal is to encourage mindful consideration of which perspective on bias researchers take in their work to facilitate a common language in research and development efforts going forward.

visual analytics, mixed-initiative systems, cognit↗

Ecosystem Services Connect Environmental Change to Human Health Outcomes

Global environmental change, driven in large part by human activities, profoundly impacts the structure and functioning of Earth’s ecosystems (Millennium Ecosystem Assessment 2005). We are beginning to push beyond planetary boundaries (Steffan et al. 2015), and the consequences for human health remain largely unknown (Myers et al. 2013). Growing evidence suggests that ecological transformations can dramatically affect human health in ways that are both obvious and obscure (Myers and Patz 2009; Myers et al. 2013). The framework of ecosystem services, designed to evaluate the benefits that people derive from ecosystem products and processes, provides a compelling framework for integrating the many factors that influence the human health response to global change, as well as for integrating health impacts into broader analyses of the impacts of this change

Bayles, Brett R.↗

Expression of cellular apoptosis susceptibility (CAS) in the human testis and testicular germ cell tumors

Testicular germ cell tumors are the most frequent malignancies found in men between 15 and 44 years old. Although cellular apoptosis susceptibility (CAS) was demonstrated to be upregulated in breast cancer and colon cancer, the expression of CAS in the human testis and testicular germ cell tumors remained elusive. In the present study, CAS-positive signals were detected in the normal testicular tissues, cancer adjacent normal testicular tissues, seminoma, yolk sac tumor, and teratoma. Interestingly, the expression level of CAS in testicular germ cell tumors (TGCTs) (but not seminoma) was significantly lower than that of human testicular tissues and cancer adjacent normal testicular tissues, suggesting that decreased CAS contributed to the progression of TGCTs. Notably, the expression of CAS in seminoma was significantly higher than that of in the non-seminomas, consistent with the results from TCGA database. Furthermore, the localization of CAS is mainly restricted in the nucleus in the lesions of normal human testicular tissue and cancer adjacent normal testicular tissue. Although the expression of CAS was not significantly different between normal testicular tissue and seminoma, CAS was more enriched in cytoplasm in seminoma compared to the normal, cancer adjacent tissue and other types of TGCTs. The current results demonstrated reduced expression of CAS in the human testicular germ cell tumors and the CAS translocation from the nuclear to cytoplasm in seminoma, thereby supporting a possible role in normal testis function and in the development of seminoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

60 APPLIED LIFE SCIENCES↗

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

60 APPLIED LIFE SCIENCES↗

GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

60 APPLIED LIFE SCIENCES↗

A systematic analysis of acceptor specificity and reaction kinetics of five human α(2,3)sialyltransferases: Product inhibition studies illustrate reaction mechanism for ST3Gal-I

Sialyltransferases (STs) catalyze the addition of sialic acids to the non-reducing ends of glycoproteins and glycolipids. In this work, we examined the acceptor specificity of five human α(2,3)sialyltransferases, namely ST3Gal -I, -II, -III, -IV and -VI. K{sub M} values for each of these enzymes is presented using radioactivity for acceptors containing Type-I (Galβ1,3GlcNAc), Type-II (Galβ1,4GlcNAc), Type-III (Galβ1,3GalNAc) and Core-2 (Galβ1,3(GlcNAcβ1,6)GalNAc) reactive groups. Several variants of acceptors inhibited ST3Gal activity emphasizing structural role of acceptor in enzyme-catalyzed reactions. In some cases, mass spectrometry was performed for structural verification. The results demonstrate human ST3Gal-I catalysis towards Type-III and Core-2 acceptors with K{sub M} = 5–50 μM and high V{sub Max} values. The K{sub M} for ST3Gal-I and ST3Gal-II was 100 and 30-fold lower, respectively, for Type-III compared to Type-I acceptors. Variants of Type-I and Type-II structures characterized ST3Gal-III, -IV and -VI for their catalytic specificity. This manuscript also estimates K{sub M} for human ST3Gal-VI using Type-I and Type-II substrates. Together, these findings built a platform for designing inhibitors of STs having therapeutic potential. - Highlights: • K{sub M} for five Human ST3Gals is reported towards Type-I, Type-II & Type-III acceptors. • LC-MS simultaneously quantifies CMP-Neu5Ac & Glycans in a sialylation reaction. • Efficient Core2 sialylation indicates co-operativitiy between ST3Gal-I & C2GnT1. • ST3Gal-I inhibition study proposes iso- or random-sequential bi-bi mechanism.

60 APPLIED LIFE SCIENCES↗

Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α

Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5′ deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the −111 to −42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except −42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the −111/+384 LXRα promoter but not of the −42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the −50 to −40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells. - Highlights: • The human LXRα promoter contains a HNF-4α specific binding motif in the proximal −50/−40 region. • Mutations in this motif abolished HNF4α binding and transactivation of the hLXRα promoter. • Silencing of HNF-4α was associated with reduced LXRα protein levels and promoter activity. • The HNF-4α/LXRα axis may have a wide role in cell and plasma cholesterol homeostasis.

60 APPLIED LIFE SCIENCES↗

Fibulin-4 is a novel Wnt/β-Catenin pathway activator in human osteosarcoma

Fibulin-4, an extracellular glycoprotein implicated in connective tissue development and elastic fiber formation, draws increasing focuses in cancer research. However, little is known about the underlying oncogenic roles of Fibulin-4 in human osteosarcoma (OS). In this study, by immunohistochemical analysis, upregulated expression of Fibulin-4 was found in the OS clinical specimens and cell lines compared to their normal counterparts. Fibulin-4 was positively correlated with the T stage of OS patients, and the proliferation index Ki67. Based on informatics analysis and functional verification, microRNA-137 was identified as a potential upstream regulator of Fibulin-4. Knockdown of Fibulin-4 or introduction of microRNA-137 inhibited cell proliferation and promoted cell apoptosis, and adverse effects were observed by overexpression of Fibulin-4. Furthermore, the tumor-suppressive functions of microRNA-137 were markedly abolished by restoration of Fibulin-4 expression in OS cells. Mechanistically, Fibulin-4 activated Wnt/β-Catenin pathway and promoted the expression of its downstream targets, including CCND2, c-Myc and VEGF. Taken together, Fibulin-4 plays critical neoplastic roles in tumor growth of human OS by activating Wnt/β-Catenin signaling and may represent a potential therapeutic target. -- Highlights: •Upregulated Fibulin-4 correlates tumor growth in human OS. •MicroRNA-137 is a critical regulator of Fibulin-4 expression. •Deregulated miR-137/Fibulin-4 axis promotes tumor growth of human OS. •Wnt/β-Catenin pathway is activated by Fibulin-4 stimulation.

60 APPLIED LIFE SCIENCES↗

Myricetin is a novel inhibitor of human inosine 5′-monophosphate dehydrogenase with anti-leukemia activity

Human inosine 5′-monophosphate dehydrogenase (hIMPDH) is a rate-limiting enzyme in the de novo biosynthetic pathway of purine nucleotides, playing crucial roles in cellular proliferation, differentiation, and transformation. Dysregulation of hIMPDH expression and activity have been found in a variety of human cancers including leukemia. In this study, we found that myricetin, a naturally occurring phytochemical existed in berries, wine and tea, was a novel inhibitor of human type 1 and type 2 IMPDH (hIMPDH1/2) with IC{sub 50} values of 6.98 ± 0.22 μM and 4.10 ± 0.14 μM, respectively. Enzyme kinetic analysis using Lineweaver-Burk plot revealed that myricetin is a mix-type inhibitor for hIMPDH1/2. Differential scanning fluorimetry and molecular docking simulation data demonstrate that myricetin is capable of binding with hIMPDH1/2. Myricetin treatment exerts potent anti-proliferative and pro-apoptotic effects on K562 human leukemia cells in a dose-dependent manner. Importantly, cytotoxicity of myricetin on K562 cells were markedly attenuated by exogenous addition of guanosine, a salvage pathway of maintaining intracellular pool of guanine nucleotides. Taking together, these results indicate that natural product myricetin exhibits potent anti-leukemia activity by interfering with purine nucleotides biosynthetic pathway through the suppression of hIMPDH1/2 catalytic activity. - Highlights: • Myricetin, a common dietary flavonoid, is a novel inhibitor of hIMPDH1/2. • Myricetin directly binds with hIMPDH1/2 and induces cell cycle arrest and apoptosis of leukemia cells. • The cytotoxicity of myricetin on K562 cells is markedly attenuated by exogenous addition of guanosine.

60 APPLIED LIFE SCIENCES↗

A human Fab exclusively binding to the extracellular domain of LMP2A

In the areas of North Africa, Southeast Asia as well as South China, Nasopharyngeal carcinoma (NPC) is among the most widespread cancers. Plenty of research findings confirmed that Epstein-Barr virus (EBV) played a crucial role in NPC. EBV-encoded Latent membrane protein 2A (LMP2A) which continuously expressed in cell membrane protein induced an epithelial-mesenchymal transition and increased the number of side population stem-like cancer cells in NPC. This reveals that LMP2A could contribute to the development and recurrence in NPC. Above evidences suggest that LMP2A could be the potential target molecule in the treatment of NPC. In the current study, a novel human antibody Fab (Fab29) against the extracellular domain of LMP2A was produced with success. Through immunofluorescence experiment it was proved that human antibody Fab29 exclusively combined the surface of SUNE cells (LMP2A-positive). Then flow cytometry result exhibited that the fluorescent intensities of SUNE cells and CNE cells were distinct (96.89% and 0.02% respectively). After that, it was shown by affinity test that the Fab29 fragment had high affinity (KD (M) 1.79E-09) with LMP2A. It was also revealed by immunohistochemical analysis that the Fab29 fragment could combine with LMP2A-positive human NPC tissues in comparison with the control group. Finally, the MTT result indicated that the Fab29 fragment could inhibit the proliferation of LMP2A-positive NPC cells. The inhibiting rate to SUNE cell proliferation reached a peak by Fab29 (19.67%) compared with unrelated Fab and CNE with Fab29 at a concentration of 500 μg/L in first 24 h and in the next 24 h the inhibition rate grew to 22.54%. In brief, it was shown that Fab29, a characteristic human antibody, could recognize LMP2A protein and inhibit the proliferation of LMP2A-expressing NPC cells in vitro.

60 APPLIED LIFE SCIENCES↗

Gab3 is required for human colorectal cancer cell proliferation

Here, we focused on the potential function of Gab3, an uncommon Gab family protein, in human colorectal cancer (CRC) cells. We found that Gab3 was only expressed in human colon cancer tissues as well as in established (HCT-116 and HT-29 lines) and primary human CRC cells. It was however absent in normal human colon cancer tissues and in FHC colon epithelial cells. Knockdown of Gab3 by targeted-shRNAs inhibited proliferation of the CRC cells. Reversely, exogenous over-expression of Gab3 promoted CRC cell proliferation. At the signaling level, Gab3 co-precipitated with p85 and SHP2 in CRC cells, which was required for subsequent Akt and Erk activation. Gab3 shRNA knockdown inhibited Akt and Erk activation, yet Gab3 over-expression augmented it. In vivo, HCT-116 xenograft tumor growth in severe combined immune deficient (SCID) mice was suppressed following expressing Gab3 shRNAs. Meanwhile, Akt and Erk activation in Gab3 shRNA-expressing tumors was also largely inhibited. Together, our results suggest that Gab3 expression in CRC cells is important for Akt-Erk activation and cell proliferation. - Highlights: • Gab3 is only expressed in colorectal cancer (CRC) cells, but not in colon epithelial cells. • Gab3 shRNA knockdown inhibits CRC cell proliferation. • Exogenous over-expression of Gab3 promotes HCT-116 cell proliferation. • Gab3 co-precipitates with p85 and SHP2 to mediate Akt and Erk activation in CRC cells. • HCT-116 tumor growth in SCID mice is suppressed with expression of Gab3 shRNAs.

60 APPLIED LIFE SCIENCES↗

Identification and molecular cloning of novel transcripts of the human kallikrein-related peptidase 10 (KLK10) gene using next-generation sequencing

Tissue kallikrein and kallikrein-related peptidases (KLKs) form the largest group of serine proteases in the human genome, sharing many structural and functional characteristics. Multiple alternative transcripts have been reported for the most human KLK genes, while many of them are aberrantly expressed in various malignancies, thus possessing significant prognostic and/or diagnostic value. Alternative splicing of cancer-related genes is a common cellular mechanism accounting for cancer cell transcriptome complexity, as it affects cell cycle control, proliferation, apoptosis, invasion, and metastasis. In this study, we describe the identification and molecular cloning of eight novel transcripts of the human KLK10 gene using 3′ rapid amplification of cDNA ends (3′ RACE) and next-generation sequencing (NGS), as well as their expression analysis in a wide panel of cell lines, originating from several distinct cancerous and normal tissues. Bioinformatic analysis revealed that the novel KLK10 transcripts contain new alternative splicing events between already annotated exons as well as novel exons. In addition, investigation of their expression profile in a wide panel of cell lines was performed with nested RT-PCR using variant-specific pairs of primers. Since many KLK mRNA transcripts possess clinical value, these newly discovered alternatively spliced KLK10 transcripts appear as new potential biomarkers for diagnostic and/or prognostic purposes or as targets for therapeutic strategies. - Highlights: • NGS was used to identify novel transcripts of the human KLK10 gene. • 8 novel KLK10 transcripts were identified. • A novel 3′UTR was detected and characterized. • The expression profiles of all 8 novel KLK10 transcripts were identified.

60 APPLIED LIFE SCIENCES↗

Airborne polycyclic aromatic hydrocarbons trigger human skin cells aging through aryl hydrocarbon receptor

Accumulating evidence suggests that polycyclic aromatic hydrocarbons (PAH) which adsorbed on the surface of ambient air particulate matters (PM), are the major toxic compound to cause cardiovascular and respiratory diseases, even cancer. However, its detrimental effects on human skin cell remain unclear. Here, we demonstrated that SRM1649b, a reference urban dust material of PAH, triggers human skin cells aging through cell cycle arrest, cell growth inhibition and apoptosis. Principally, SRM1649b facilitated Aryl hydrocarbon receptor (AhR) translocated into nucleus, subsequently activated ERK/MAPK signaling pathway, and upregulated aging-related genes expression. Most important, we found that AhR antagonist efficiently revert the aging of skin cells. Thus our novel findings firstly revealed the mechanism of skin aging under PAH contamination and provided potential strategy for clinical application. - Highlights: • SRM1649b inhibited the proliferation and lead to cell cycle arrest in human skin cells. • SRM1649b promoted apoptosis of human skin cells and induced cell aging. • SRM1649b caused AhR translocation into nucleus and upregulated aging-related genes. • The expression of aging-related genes were inhibited by AhR antagonist.

60 APPLIED LIFE SCIENCES↗

Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis

The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca{sup 2+} level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca{sup 2+} and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca{sup 2+} homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages. - Highlights: • Salubrinal protects human dermal fibroblasts against UV radiation induced cell death. • UV-B induces ER stress response in human dermal fibroblast. • Salubrinal has protective effects on UV-B induced ER stress response. • Salubrinal regulates the intracellular Ca{sup 2+} level in UV-B treated human dermal fibroblasts.

60 APPLIED LIFE SCIENCES↗

Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells

Highlights: • Salinomycin analogs show increased activity against colorectal cancer cells. • Low micromolar concentrations result in inhibition of proliferation and migration. • High micromolar concentrations induce apoptotic cell death. • Salinomycin analogs show cancer stem cell specifity. Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin.

60 APPLIED LIFE SCIENCES↗