The positive feedback loop between Nrf2 and phosphogluconate dehydrogenase stimulates proliferation and clonogenicity of human hepatoma cells

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.Recent studies report that nuclear factor-erythroid-2-related factor 2 (Nrf2) facilitates tumor progression through metabolic reprogramming in cancer cells. However, the molecular mechanism underlying the oncogenic functions of Nrf2 is not yet well understood. Some of the pentose phosphate pathway (PPP) enzymes are considered to play a role in the cancer progression. The present study was intended to explore the potential role of phosphogluconate dehydrogenase (PGD), one of the PPP enzymes, in the proliferation and migration of human hepatoma HepG2 cells. Genetic ablation of Nrf2 attenuated the expression of PGD at both transcriptional and translational levels. Notably, Nrf2 regulates the transcription of PGD through direct binding to the antioxidant response element in its promoter region. Nrf2 overexpression in HepG2 cells led to increased proliferation, survival, and migration, and these events were suppressed by silencing PGD. Interestingly, knockdown of the gene encoding this enzyme not only attenuated the proliferation and clonogenicity of HepG2 cells but also downregulated the expression of Nrf2. Thus, there seems to exist a positive feedback loop between Nrf2 and PGD which is exploited by hepatoma cells for their proliferation and survival. Treatment of HepG2 cells with ribulose-5-phosphate, a catalytic product of PGD, gave rise to a concentration-dependent upregulation of Nrf2. Collectively, the current study shows that Nrf2 promotes hepatoma cell growth and progression, partly through induction of PGD transcription.

Cutaneous Polyarteritis Nodosa Presented with Digital Gangrene: A Case Report

Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of vasculitis involving small and medium sized arteries of unknown etiology. The disease can be differentiated from polyarteritis nodosa by its limitation to the skin and lack of progression to visceral involvement. The characteristic manifestations are subcutaneous nodule, livedo reticularis, and ulceration, mostly localized on the lower extremity. Arthralgia, myalgia, peripheral neuropathy, and constitutional symptoms such as fever and malaise may also be present. We describe a 34-yr-old woman presented with severe ischemic change of the fingertip and subcutaneous nodules without systemic manifestations as an unusual initial manifestation of CPAN. Therapy with corticosteroid and alprostadil induce a moderate improvement of skin lesions. However, necrosis of the finger got worse and the finger was amputated

Prognostic influence of body mass index and body weight gain during adjuvant FOLFOX chemotherapy in Korean colorectal cancer patients

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background: Asian population has different body mass index (BMI) profile compared to Caucasian population. However, the effect of obesity and body weight gain in Asian colorectal cancer patients treated with adjuvant chemotherapy has not been studied thus far. Methods: We have analyzed the association between disease-free survival (DFS) and obesity/body weight change during treatment in Korean stage III or high-risk stage II colorectal cancer patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin. BMI was classified according to WHO Asia-Pacific classification. Weight change was calculated by comparing body weights measured at the last chemotherapy cycle and before surgery. Results: Among a total of 522 patients, 35.7 % of patients were obese (BMI >= 25 kg/m(2)) and 29.1 % were overweight (BMI, 23-24.9 kg/m(2)) before surgery. 18.0 % of patients gained = 5 kg and 26.1 % gained 2-4.9 kg during the adjuvant chemotherapy period. Baseline BMI or body weight change was not associated with DFS in the overall study population. However, body weight gain (>= 5 kg) was associated with inferior DFS (adjusted hazard ratio 2.04, 95 % confidence interval 1.02-4.08, p = 0.043) in overweight and obese patients (BMI >= 23.0 kg/m(2)). Conclusion: In Korean colorectal cancer patients treated with adjuvant FOLFOX chemotherapy, body weight gain during the treatment period has a negative prognostic influence in overweight and obese patients

An Earth-mass planet in a time of COVID-19: KMT-2020-BLG-0414Lb

We report the discovery of KMT-2020-BLG-0414Lb, with a planet-to-host mass ratio q2 = 0:9- 1:2 × 10-5 = 3-4 q⊕ at 1σ, which is the lowest mass-ratio microlensing planet to date. Together with two other recent discoveries (4. q=q⊕. 6), it fills out the previous empty sector at the bottom of the triangular (log s; log q) diagram, where s is the planet-host separation in units of the angular Einstein radius θE. Hence, these discoveries call into question the existence, or at least the strength, of the break in the mass-ratio function that was previously suggested to account for the paucity of very low-q planets. Due to the extreme magnification of the event, Amax ∼ 1450 for the underlying single-lens event, its light curve revealed a second companion with q3 ∼ 0:05 and j log s3j ∼ 1, i.e., a factor ∼ 10 closer to or farther from the host in projection. The measurements of the microlens parallax ∼E and the angular Einstein radius ∼E allow estimates of the host, planet and second companion masses, (M1;M2;M3) ∼ (0:3M⊙; 1:0M⊙; 17MJ ), the planet and second companion projected separations, (a⊥;2; a⊥;3) ∼ (1:5; 0:15 or 15) au, and system distance DL ∼ 1 kpc. The lens could account for most or all of the blended light (I ∼ 19:3) and so can be studied immediately with high-resolution photometric and spectroscopic observations that can further clarify the nature of the system. The planet was found as part of a new program of high-cadence follow-up observations of high-magnification events. The detection of this planet, despite the considerable difficulties imposed by COVID-19 (two KMT sites and OGLE were shut down), illustrates the potential utility of this program

A Nuclear Localization of the Infectious Haematopoietic Necrosis Virus NV Protein Is Necessary for Optimal Viral Growth

The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection in RTG-2 cells of NV fused to green fluorescent protein (GFP), a nuclear localization of NV was demonstrated. Deletion analyses showed that the 32EGDL35 residues were essential for nuclear localization of NV protein, and fusion of these 4 amino acids to GFP directed its transport to the nucleus. We generated a recombinant IHNV, rIHNV-NV-ΔEGDL in which the 32EGDL35 was deleted from the NV. rIHNVs with wild-type NV (rIHNV-NV) or with the NV gene replaced with GFP (rIHNV-ΔNV-GFP) were used as controls. RTG-2 cells infected with rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL yielded 12- and 5-fold less infectious virion, respectively, than wild type rIHNV-infected cells at 48 h post-infection (p.i.). While treatment with poly I∶C at 24 h p.i. did not inhibit replication of wild-type rIHNVs, replication rates of rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL were inhibited by poly I∶C. In addition, both rIHNV-ΔNV and rIHNV-NV-ΔEGDL induced higher levels of expressions of both IFN1 and Mx1 than wild-type rIHNV. These data suggest that the IHNV NV may support the growth of IHNV through inhibition of the INF system and the amino acid residues of 32EGDL35 responsible for nuclear localization are important for the inhibitory activity of NV

Development of an electrooculogram-based eye-computer interface for communication of individuals with amyotrophic lateral sclerosis

Abstract Background Electrooculogram (EOG) can be used to continuously track eye movements and can thus be considered as an alternative to conventional camera-based eye trackers. Although many EOG-based eye tracking systems have been studied with the ultimate goal of providing a new way of communication for individuals with amyotrophic lateral sclerosis (ALS), most of them were tested with healthy people only. In this paper, we investigated the feasibility of EOG-based eye-writing as a new mode of communication for individuals with ALS. Methods We developed an EOG-based eye-writing system and tested this system with 18 healthy participants and three participants with ALS. We also applied a new method for removing crosstalk between horizontal and vertical EOG components. All study participants were asked to eye-write specially designed patterns of 10 Arabic numbers three times after a short practice session. Results Our system achieved a mean recognition rates of 95.93% for healthy participants and showed recognition rates of 95.00%, 66.67%, and 93.33% for the three participants with ALS. The low recognition rates in one of the participants with ALS was mainly due to miswritten letters, the number of which decreased as the experiment proceeded. Conclusion Our proposed eye-writing system is a feasible human-computer interface (HCI) tool for enabling practical communication of individuals with ALS

New Method for Pure-Tone Audiometry Using Electrooculogram: A Proof-of-Concept Study

Precise and timely evaluation of an individual’s hearing loss plays an important role in determining appropriate treatment strategies, including medication and aural rehabilitation. However, currently available hearing assessment systems do not satisfy the need for an objective assessment tool with a simple and non-invasive procedure. In this paper, we propose a new method for pure-tone audiometry, which may potentially be used to assess an individual’s hearing ability objectively and quantitatively, without need for the user’s active response. The proposed method is based on the auditory oculogyric reflex, where the eyes involuntary rotate towards the source of a sound, in response to spatially moving pure-tone audio stimuli modulated at specific frequencies and intensities. We quantitatively analyzed horizontal electrooculograms (EOG) recorded with a pair of electrodes under two conditions—when pure-tone stimuli were (1) “inaudible” or (2) “audible” to a participant. Preliminary experimental results showed significantly increased EOG amplitude in the audible condition compared to the inaudible condition for all ten healthy participants. This demonstrates potential use of the proposed method as a new non-invasive hearing assessment tool