Roles of ABCC1 and ABCC4 in Proliferation and Migration of Breast Cancer Cell Lines

ABCC1 and ABCC4 utilize energy from ATP hydrolysis to transport many different molecules, including drugs, out of the cell and, as such, have been implicated in causing drug resistance. However recently, because of their ability to transport signaling molecules and inflammatory mediators, it has been proposed that ABCC1 and ABCC4 may play a role in the hallmarks of cancer development and progression, independent of their drug efflux capabilities. Breast cancer is the most common cancer affecting women. In this study, the aim was to investigate whether ABCC1 or ABCC4 play a role in the proliferation or migration of breast cancer cell lines MCF-7 (luminal-type, receptor-positive) and MDA-MB-231 (basal-type, triple-negative). The effects of small molecule inhibitors or siRNA-mediated knockdown of ABCC1 or ABCCC4 were measured. Colony formation assays were used to assess the clonogenic capacity, MTT assays to measure the proliferation, and scratch assays and Transwell assays to monitor the cellular migration. The results showed a role for ABCC1 in cellular proliferation, whilst ABCC4 appeared to be more important for cellular migration. ELISA studies implicated cAMP and/or sphingosine-1-phosphate efflux in the mechanism by which these transporters mediate their effects. However, this needs to be investigated further, as it is key to understand the mechanisms before they can be considered as targets for treatment

Regulatory microRNAs in Brown, Brite and White Adipose Tissue

MicroRNAs (miRNAs) constitute a class of short noncoding RNAs which regulate gene expression by targeting messenger RNA, inducing translational repression and messenger RNA degradation. This regulation of gene expression by miRNAs in adipose tissue (AT) can impact on the regulation of metabolism and energy homeostasis, particularly considering the different types of adipocytes which exist in mammals, i.e., white adipocytes (white AT; WAT), brown adipocytes (brown AT; BAT), and inducible brown adipocytes in WAT (beige or brite or brown-in-white adipocytes). Indeed, an increasing number of miRNAs has been identified to regulate key signaling pathways of adipogenesis in BAT, brite AT, and WAT by acting on transcription factors that promote or inhibit adipocyte differentiation. For example, MiR-328, MiR-378, MiR-30b/c, MiR-455, MiR-32, and MiR-193b-365 activate brown adipogenesis, whereas MiR-34a, MiR-133, MiR-155, and MiR-27b are brown adipogenesis inhibitors. Given that WAT mainly stores energy as lipids, whilst BAT mainly dissipates energy as heat, clarifying the effects of miRNAs in different types of AT has recently attracted significant research interest, aiming to also develop novel miRNA-based therapies against obesity, diabetes, and other obesity-related diseases. Therefore, this review presents an up-to-date comprehensive overview of the role of key regulatory miRNAs in BAT, brite AT, and WAT

NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue

Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT

Improving zinc and iron biofortification in wheat through genomics approaches

Globally, about 20% of calories (energy) come from wheat. In some countries, it is more than 70%. More than 2 billion people are at risk for zinc deficiency and even more, people are at risk of iron deficiency, nearly a quarter of all children underage group of 5 are physically and cognitively stunted, and lack of dietary zinc is a major contributing factor. Biofortified wheat with elevated levels of zinc and iron has several potential advantages as a delivery vehicle for micronutrients in the diets of resource-poor consumers who depend on cereal-based diets. The conventional breeding strategies have been successful in the introduction of novel alleles for grain Zn and Fe that led to the release of competitive Zn enriched wheat varieties in South Asia. The major challenge over the next few decades will be to maintain the rates of genetic gains for grain yield along with increased grain Zn/Fe concentration to meet the food and nutritional security challenges. Therefore, to remain competitive, the performance of Zn-enhanced lines/varieties must be equal or superior to that of current non-biofortified elite lines/varieties. Since both yield and Zn content are invisible and quantitatively inherited traits except few intermediate effect QTL regions identified for grain Zn, increased breeding efforts and new approaches are required to combine them at high frequency, ensuring that Zn levels are steadily increased to the required levels across the breeding pipelines. The current review article provides a comprehensive list of genomic regions for enhancing grain Zn and Fe concentrations in wheat including key candidate gene families such NAS, ZIP, VLT, ZIFL, and YSL. Implementing forward breeding by taking advantage of the rapid cycling trait pipeline approaches would simultaneously introgress high Zn and Fe QTL into the high Zn and normal elite lines, further increasing Zn and Fe concentrations

Asprosin exerts pro-inflammatory effects in THP-1 macrophages mediated via the Toll-like receptor 4 (TLR4) pathway

Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway

Paternal low protein diet perturbs inter-generational metabolic homeostasis in a tissue-specific manner in mice

The underlying mechanisms driving paternally-programmed metabolic disease in offspring remain poorly defined. We fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using artificial insemination, in combination with vasectomised male mating, we generated offspring using either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Offspring from either LPD sperm or seminal fluid display elevated body weight and tissue dyslipidaemia from just 3 weeks of age. These changes become more pronounced in adulthood, occurring in conjunction with altered hepatic metabolic and inflammatory pathway gene expression. Second generation offspring also display differential tissue lipid abundance, with profiles similar to those of first generation adults. These findings demonstrate that offspring metabolic homeostasis is perturbed in response to a suboptimal paternal diet with the effects still evident within a second generation

Portrayal of Parent- Children Relationship in Television Drama Serials of Pakistan

Purpose: The current research investigates the portrayal of the parent- children relationship in prime-time entertainment television dramas of Pakistan. Relationship between parenting style and socio-economic status of the parents has been analyzed. Design/Methodology/Approach: Quantitative Content Analysis has been applied to measure the portrayal of parents in Drama serials. Top three entertainment channels ARY Digital, Hum TV and Geo TV were the targeted channels and parent-children based episodes were selected through purposive sampling. Out of 147 episodes, 308 scenes were selected. Scenes were coded on the predefined categories found in existing literature. Findings: The results showed that there was not much significant relationship found between socio-economic status of the parents and their parenting style. However, generation raised by parents with high socio-economic status showed submissive behavior towards their parents while the children raised by parents with low socio-economic status showed disrespectful behavior to their parents. Implications/Originality/Value: The findings suggest policy consideration to Pakistan Media Regulatory Authority regarding parents’ portrayal in drama serials. As respecting parents is our cultural value without any difference in socio economic status. But more materialistic approach is being projected in TV channels which need a second thought as the social norms

Steady-state investigation of carbon-based adsorbent-adsorbate pairs for heat transformation application

In this study, the ideal adsorption cycle behavior of eight activated carbon and refrigerant pairs is evaluated. The selected pairs are KOH6-PR/ethanol, WPT-AC/ethanol, Maxsorb-III/methanol, Maxsorb-III/CO2, Maxsorb-III/n-butane, Maxsorb-III/R-134a, SAC-2/R32 and Maxsorb-III/R507a. The following cooling performance parameters are evaluated for all pairs: specific cooling energy (SCE), concentration difference (ΔW) and coefficient of performance (COP) of ideal adsorption cooling and refrigeration cycles. The evaporator temperatures for the applications of adsorption cooling and refrigeration are selected as 7 and −5 °C, respectively. It is found that the Maxsorb-III/methanol pair has shown the highest specific cooling energy and coefficient of performance in a wide range of desorption temperatures; i.e., for the adsorption cooling cycle it has SCE and COP of 639.83 kJ/kg and 0.803, respectively, with desorption temperatures of 80 °C. The KOH6-PR/ethanol and the WPT-AC/ethanol pairs also give good performances comparable to that of the Maxsorb-III/methanol pair. However, the SAC-2/R32 pair possesses a higher concentration difference than the Maxsorb-III/methanol, KOH6-PR/ethanol and WPT-AC/ethanol pairs but shows a lower performance. This is due to the lower isosteric heat of adsorption of SAC-2/R32 compared to these pairs. It is found that Maxsorb-III/methanol, KOH6-PR/ethanol and WPT-AC/ethanol are the most promising pairs for application in designing adsorption cooling and refrigeration systems.In this study, the ideal adsorption cycle behavior of eight activated carbon and refrigerant pairs is evaluated. The selected pairs are KOH6-PR/ethanol, WPT-AC/ethanol, Maxsorb-III/methanol, Maxsorb-III/CO2, Maxsorb-III/n-butane, Maxsorb-III/R-134a, SAC-2/R32 and Maxsorb-III/R507a. The following cooling performance parameters are evaluated for all pairs: specific cooling energy (SCE), concentration difference (ΔW) and coefficient of performance (COP) of ideal adsorption cooling and refrigeration cycles. The evaporator temperatures for the applications of adsorption cooling and refrigeration are selected as 7 and −5 °C, respectively. It is found that the Maxsorb-III/methanol pair has shown the highest specific cooling energy and coefficient of performance in a wide range of desorption temperatures; i.e., for the adsorption cooling cycle it has SCE and COP of 639.83 kJ/kg and 0.803, respectively, with desorption temperatures of 80 °C. The KOH6-PR/ethanol and the WPT-AC/ethanol pairs also give good performances comparable to that of the Maxsorb-III/methanol pair. However, the SAC-2/R32 pair possesses a higher concentration difference than the Maxsorb-III/methanol, KOH6-PR/ethanol and WPT-AC/ethanol pairs but shows a lower performance. This is due to the lower isosteric heat of adsorption of SAC-2/R32 compared to these pairs. It is found that Maxsorb-III/methanol, KOH6-PR/ethanol and WPT-AC/ethanol are the most promising pairs for application in designing adsorption cooling and refrigeration systems.King Saud University, Riyadh, Saudi Arabi