Mitochondrially derived peptides represent a new class of circulating signalling molecules. Humanin, the first member of this class, has been shown to have several metabolic effects such as reducing ...weight gain and visceral fat and increasing glucose‐stimulated insulin release. The discovery of several other new members, such as MOTS‐c and SHLP1–6, has further added to this group. These new peptides have also been found to affect metabolism with MOTS‐c potently decreasing weight gain in mice on a high‐fat diet. This review covers the basic biology of this class of peptides and discusses the relevance to organismal metabolism.
Mitochondrially derived peptides regulate metabolism. Mitochondrial stress leads to changes in MOTS‐c, humanin, and SHLP levels. This in turn plays a protective role in metabolism and leads to tissue specific effects.
Vitamin D and Endothelial Function Kim, Do-Houn; Meza, Cesar A; Clarke, Holly ...
Nutrients,
02/2020, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Vitamin D is known to elicit a vasoprotective effect, while vitamin D deficiency is a risk factor for endothelial dysfunction (ED). ED is characterized by reduced bioavailability of a potent ...endothelium-dependent vasodilator, nitric oxide (NO), and is an early event in the development of atherosclerosis. In endothelial cells, vitamin D regulates NO synthesis by mediating the activity of the endothelial NO synthase (eNOS). Under pathogenic conditions, the oxidative stress caused by excessive production of reactive oxygen species (ROS) facilitates NO degradation and suppresses NO synthesis, consequently reducing NO bioavailability. Vitamin D, however, counteracts the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which produces ROS, and improves antioxidant capacity by enhancing the activity of antioxidative enzymes such as superoxide dismutase. In addition to ROS, proinflammatory mediators such as TNF-α and IL-6 are risk factors for ED, restraining NO and eNOS bioactivity and upregulating the expression of various atherosclerotic factors through the NF-κB pathway. These proinflammatory activities are inhibited by vitamin D by suppressing NF-κB signaling and production of proinflammatory cytokines. In this review, we discuss the diverse activities of vitamin D in regulating NO bioavailability and endothelial function.
Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
This review outlines problems and progress in development of solution-processed organic light-emitting diodes (SOLEDs) in industry and academia. Solution processing has several advantages such as low ...consumption of materials, low-cost processing, and large-area manufacturing. However, use of a solution process entails complications, such as the need for solvent resistivity and solution-processable materials, and yields SOLEDs that have limited luminous efficiency, severe roll-off characteristics, and short lifetime compared to OLEDs fabricated using thermal evaporation. These demerits impede production of practical SOLED displays. This review outlines the industrial demands for commercial SOLEDs and the current status of SOLED development in industries and academia, and presents research guidelines for the development of SOLEDs that have high efficiency, long lifetime, and good processability to achieve commercialization.
Highly efficient organic/inorganic hybrid perovskite light‐emitting diodes (PeLEDs) based on graphene anode are developed for the first time. Chemically inert graphene avoids quenching of excitons by ...diffused metal atom species from indium tin oxide. The flexible PeLEDs with graphene anode on plastic substrate show good bending stability; they provide an alternative and reliable flexible electrode for highly efficient flexible PeLEDs.
This paper deals with the preparation, characterization, thermal properties and thermal reliability of form-stable composite phase change materials (PCMs), composed of n-octadecane, expanded ...vermiculite, and perlite for thermal energy storage. The composite PCMs were prepared by incorporation of liquid n-octadecane within the expanded vermiculite (eVMT) and expanded perlite (ePLT), using a vacuum impregnation method. The microstructures of n-octadecane/expanded vermiculite and pearlite were characterized by scanning electron microscopy (SEM). Analysis of Fourier transform infrared spectroscopy (FT-IR) of the prepared composite PCMs showed good compatibility between n-octadecane and the expanded vermiculite and pearlite. The thermal conductivities of composites were reduced, based on the TCi results. Differential scanning calorimetry (DSC) analysis indicated that the n-octadecane/eVMT and n-odtadecane/ePLT composites maintained their large latent heat capacity and original phase change temperatures, due to large surface area and good dispersion of the eVMT and ePLT. TGA analysis revealed that the prepared composite PCMs had good thermal durability in the working temperature ranges. Therefore, n-octadecane based composite PCMs can be considered as suitable candidates for latent heat thermal energy storage, with high thermal performance.
•Paraffinic PCMs/expanded vermiculite and perlite composites were prepared for efficient thermal energy storage.•The composite PCMs were prepared by incorporation of liquid n-octadecane using a vacuum impregnation method.•The composite PCMs showed good dispersion and compatibility.•The composite PCMs maintained good thermal properties.
The present study was conducted to investigate growth performance, carcass characteristics, short-chain fatty acids, fatty acid composition in abdominal fat, and serum parameters in broiler chickens ...fed diets containing corn oil, coconut oil, or black soldier fly larvae (BSFL) oil at the level of 50 g per kg of diet during the 30-day-feeding period. A total 450 one-day-old male broiler chicks (Ross 308) were randomly allocated to one of 3 dietary groups. Each treatment had 10 replicates with 15 chicks per replicate. Feed conversion ratio was decreased in the coconut and BSFL oil group compared with the corn oil group. Dietary BSFL oil increased ileal weight-to-length ratio at day 30 after hatch. Dietary BSFL oil increased significantly ileal branched-chain fatty acid (P < 0.05) and moderately total short-chain fatty acid in 15-day-old broilers (P = 0.074). At day 30, ileal propionate was highest in the coconut oil group but cecal propionate was highest (P < 0.05) in the BSFL oil group. Fatty acid composition of abdominal fat was affected by dietary fat sources. Especially, chickens fed diets containing coconut oil or BSFL oil had higher contents (P < 0.05) of saturated fatty acid being dominant in lauric and myristic acids compared with those fed on corn oil. On the other hand, the reverse trend was noted (P < 0.05) as to polyunsaturated fatty acids being dominant in corn oil compared with coconut oil and BSFL oil. Coconut oil vs. corn oil significantly increased total and high-density lipoprotein cholesterol. Finally, BSFL oil vs. corn oil significantly increased total antioxidant capacity in chickens. It is concluded that dietary BSFL oil improves feed conversion ratio and increases the incorporation of medium-chain fatty acids into abdominal fat pad and serum antioxidant capacity in broiler chickens.
The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular ...mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1-6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.
RAS proteins play critical roles in various cellular processes, including growth and transformation. RAS proteins are subjected to protein stability regulation via the Wnt/β‐catenin pathway, and ...glycogen synthase kinase 3 beta (GSK3β) is a key player for the phosphorylation‐dependent RAS degradation through proteasomes. GSK3β‐mediated RAS degradation does not occur in cells that express a nondegradable mutant (MT) β‐catenin. Here, we show that β‐catenin directly interacts with RAS at the α‐interface region that contains the GSK3β phosphorylation sites, threonine 144 and threonine 148 residues. Exposure of these sites by prior β‐catenin degradation is required for RAS degradation. The introduction of a peptide that blocks the β‐catenin‐RAS interaction by binding to β‐catenin rescues the GSK3β‐mediated RAS degradation in colorectal cancer (CRC) cells that express MT β‐catenin. The coregulation of β‐catenin and RAS stabilities by the modulation of their interaction provides a mechanism for Wnt/β‐catenin and RAS‐ERK pathway cross‐talk and the synergistic transformation of CRC by both APC and KRAS mutations.
Synopsis
GSK3β promotes phosphorylation‐ and polyubiquitination‐dependent proteasomal RAS degradation. β‐Catenin directly interacts with RAS, thereby preventing GSK3β‐dependent phosphorylation and degradation, defining the basis for the synergistic effect of β‐catenin and RAS on cancer growth.
β‐Catenin directly interacts with RAS at the α‐interface that contains GSK3β phosphorylation sites.
β‐Catenin degradation is required for subsequent GSK3β‐mediated RAS degradation.
Targeting both β‐catenin and RAS for degradation is a potential approach against colorectal cancer.
GSK3β promotes phosphorylation‐ and polyubiquitination‐dependent proteasomal RAS degradation. β‐Catenin directly interacts with RAS, thereby preventing GSK3β‐dependent phosphorylation and degradation, defining the basis for the synergistic effect of β‐catenin and RAS on cancer growth.
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