High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis

To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis

Effects of driving style and bedding in pigs transported to slaughterhouse in different temperatures

Animal welfare during transport became an largely issue because of increasing demand for improved animal welfare standards. Most studies on the animal welfare during transportation have concentrated on the atmosphere and the temperature of the truck compartments. Thus, the objective of study was to collect and quantify three axis acceleration and determine the effect of bedding for transporting pigs from farm to slaughterhouse. A total of 2,840 crossbred fattening pigs with a live weight of approximately 115 kg were used. They were raised in the same commercial farms and transported to the same commercial slaughterhouse. A 3×2×2 completely randomized factorial design was used to investigate effects of rubber type bedding (bedding or non-bedding) and two levels of driving style (aggressive or normal) in three different time periods with different outside temperatures. Air temperature treatments were as follow: high temperature ([HT] higher than 24°C); low temperature ([LT] lower than 10°C); normal temperature ([NT] 10°C to 24°C). In our experiment, pigs transported under aggressive driving style showed lower (p < 0.05) pH and water holding capacity (WHC) than those transported under normal driving style. Pigs transported under normal driving style showed a lower percentage of drip loss (DL) (p < 0.05) than those transported with an aggressive driving style. Also, transported with bedding showed higher (p < 0.05) lying behavior but lower (p < 0.05) sitting behavior than those transported without bedding. Pigs transported under normal driving style showed lower (p < 0.05) cortisol level than those transported under aggressive driving style. In conclusion, aggressive driving style cause acute stress in pigs, while bedding helps alleviate acute stress in pigs during transportation in LT

The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response

Background: Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods: To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene. Results: PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies. Conclusions: These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells. © 2020, The Author(s).1

Exosome Proteome of U-87MG Glioblastoma Cells

Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus. Cell culture medium was collected, and exosomes were isolated by continuous centrifugation eliminating cell debris, nucleic acids, and other particles. The morphology of exosomes was observed by cryo-tunneling electron microscopy. According to 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, certain proteins including collagen type VI alpha 1, putative RNA-binding protein 15B chain A, substrate induced remodeling of the active site regulates HTRA1, coatomer protein complex-subunit beta 2, myosin-heavy chain 1, and keratin-type I cytoskeletal 9 showed differences between the control proteome and the low temperature-exposed proteome

Vitamin C in Cancer: A Metabolomics Perspective

There is an ongoing interest in cellular antioxidants and oxidants as well as cellular mechanisms underlying their effects. Several reports suggest that vitamin C (L-ascorbic acid) functions as a pro-oxidant with selective toxicity against specific types of tumor cells. In addition, reduced glutathione plays an emerging role in reducing oxidative stress due to xenobiotic toxins such as metals and oxidants associated with diseases such as cancer, cardiovascular disease, and stroke. High-dose intravenous vitamin C and intravenous glutathione have been used as complementary, alternative, and adjuvant medicines. Here, we review the molecular mechanisms underlying the regulation of oxidation/reduction systems, focusing on the altered metabolomics profile in cancer cells following treatment with pharmacological vitamin C. This review focuses on the role of vitamin C in energy metabolism in terms of adenosine triphosphate, cysteine, and reduced glutathione levels, affecting cancer cell death

Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress

It is well known that oxidative stress induces muscle atrophy, which decreases with the activation of Nrf2/HO-1. Fermented oyster extracts (FO), rich in γ-aminobutyric acid (GABA) and lactate, have shown antioxidative effects. We evaluated whether FO decreased oxidative stress by upregulating Nrf2/HO-1 and whether it decreased NF-κB, leading to decreased IL-6 and TNF-α. Decreased oxidative stress led to the downregulation of Cbl-b ubiquitin ligase, which increased IGF-1 and decreased FoxO3, atrogin1, and Murf1, and eventually decreased muscle atrophy in dexamethasone (Dexa)-induced muscle atrophy animal model. For four weeks, mice were orally administered with FO, GABA, lactate, or GABA+Lactate, and then Dexa was subcutaneously injected for ten days. During Dexa injection period, FO, GABA, lactate, or GABA+Lactate were also administered, and grip strength test and muscle harvesting were performed on the day of the last Dexa injection. We compared the attenuation effect of FO with GABA, lactate, and GABA+lactate treatment. Nrf2 and HO-1 expressions were increased by Dexa but decreased by FO; SOD activity and glutathione levels were decreased by Dexa but increased by FO; NADPH oxidase activity was increased by Dexa but decreased by FO; NF-κB, IL-6, and TNF-α activities were increased by Dexa were decreased by FO; Cbl-b expression was increased by Dexa but restored by FO; IGF-1 expression was decreased by Dexa but increased by FO; FoxO3, Atrogin-1, and MuRF1 expressions were increased by Dexa but decreased by FO. The gastrocnemius thickness and weight were decreased by Dexa but increased by FO. The cross-sectional area of muscle fiber and grip strength were decreased by Dexa but increased by FO. In conclusion, FO decreased Dexa-induced oxidative stress through the upregulation of Nrf2/HO-1. Decreased oxidative stress led to decreased Cbl-b, FoxO3, atrogin1, and MuRF1, which attenuated muscle atrophy

Rice Germ Attenuates Chronic Unpredictable Mild Stress-Induced Muscle Atrophy

Chronic stress leads to hypothalamic–pituitary–adrenal axis dysfunction, increasing cortisol levels. Glucocorticoids (GCs) promote muscle degradation and inhibit muscle synthesis, eventually causing muscle atrophy. In this study, we aimed to evaluate whether rice germ supplemented with 30% γ-aminobutyric acid (RG) attenuates muscle atrophy in an animal model of chronic unpredictable mild stress (CUMS). We observed that CUMS raised the adrenal gland weight and serum adrenocorticotropic hormone (ACTH) and cortisol levels, and these effects were reversed by RG. CUMS also enhanced the expression of the GC receptor (GR) and GC–GR binding in the gastrocnemius muscle, which were attenuated by RG. The expression levels of muscle degradation-related signaling pathways, such as the Klf15, Redd-1, FoxO3a, Atrogin-1, and MuRF1 pathways, were enhanced by CUMS and attenuated by RG. Muscle synthesis-related signaling pathways, such as the IGF-1/AKT/mTOR/s6k/4E-BP1 pathway, were reduced by CUMS and enhanced by RG. Moreover, CUMS raised oxidative stress by enhancing the levels of iNOS and acetylated p53, which are involved in cell cycle arrest, whereas RG attenuated both iNOS and acetylated p53 levels. Cell proliferation in the gastrocnemius muscle was reduced by CUMS and enhanced by RG. The muscle weight, muscle fiber cross-sectional area, and grip strength were reduced by CUMS and enhanced by RG. Therefore, RG attenuated ACTH levels and cortisol-related muscle atrophy in CUMS animals

Attenuation Effect of Radiofrequency Irradiation on UV-B-Induced Skin Pigmentation by Decreasing Melanin Synthesis and through Upregulation of Heat Shock Protein 70

Excess melanin deposition in the skin causes cosmetic problems. HSP70 upregulation decreases microphthalmia-associated transcription factor (MITF) expression, which eventually decreases tyrosinase activity and melanogenesis. Ultraviolet (UV) radiation upregulates p53, which increases the melanocortin receptor (MC1R) and MITF. Furthermore, HSP70 decreases p53 and radiofrequency irradiation (RF) increases HSP70. We evaluated whether RF increased HSP70 and decreased p53, consequently decreasing the MITF/tyrosinase pathway and melanogenesis in UV-B radiated animal skin. Various RF combinations with 50, 100, and 150 ms and 5, 10, and 15 W were performed on the UV-B radiated mouse skin every 2 d for 28 d. When RF was performed with 100 ms/10 W, melanin deposition, evaluated by Fontana–Masson staining, decreased without skin crust formation in the UV-B radiated skin. Thus, we evaluated the effect of RF on decreasing melanogenesis in the HEMn and UV-B radiated skin at a setting of 100 ms/10 W. HSP70 expression was decreased in the UV-B radiated skin but was increased by RF. The expression of p53, MC1R, and MITF increased in the UV-B radiated skin but was decreased by RF. The expression of p53, MC1R, and MITF increased in the α-MSH treated HEMn but was decreased by RF. The decreasing effects of RF on p53, MC1R, CREB and MITF were higher than those of HSP70-overexpressed HEMn. The decreasing effect of RF on p53, MC1R, CREB, and MITF disappeared in the HSP70-silenced HEMn. MC1R, CREB, and MITF were not significantly decreased by the p53 inhibitor in α-MSH treated HEMn. RF induced a greater decrease in MC1R, CREB, and MITF than the p53 inhibitor. Therefore, RF may have decreased melanin synthesis by increasing HSP70 and decreasing p53, thus decreasing MC1R/CREB/MITF and tyrosinase activity

The Phlorotannin-Rich Fraction of Ecklonia cava Extract Attenuated the Expressions of the Markers Related with Inflammation and Leptin Resistance in Adipose Tissue

Obesity is associated with systemic chronic inflammation, and it induces central leptin resistance which blocks the appetite-suppressing effect of leptin and leptin resistance in adipocytes. In the present study, we evaluated the effects of Ecklonia cava extract (ECE), which contained rich phlorotannins, on inflammation and leptin resistance in the adipose tissue of a diet-induced obese model. Effects of ECE on fat deposition, inflammation, M1/M2 macrophage, and T-cell infiltrations were investigated, and leptin resistance and SOCS3 were also measured in adipose tissue. Furthermore, ECE attenuated the expression of inflammation-related receptors such as TLR4 and RAGE and leptin resistance by reducing SOCS3 expression, increasing expression of leptin receptor in adipose tissue, and increasing lipolysis. ECE showed antiadiposity and anti-inflammatory effects, attenuated leptin resistance, and increased lipolysis in the diet-induced obese model. This study shows that ECE is a suitable dietary supplement candidate for the prevention or treatment of obesity or obesity-associated diseases, especially inflammation-related diseases

Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers (eIF2α phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone-and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases. © The Korean Society for Molecular and Cellular Biology. All rights reserved.1