Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration

Scale-up study for ex-vivo expansion of allogeneic natural killer cells in stirred-tank bioreactor

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be considered as optimal alternative system for large-scale NK cell expansion compared with other ones because it is automated, less labor intensive, scalable, well-controlled and cost-effective. In bioreactor process, agitation is one of important parameters for NK cell expansion because it is necessary to provide homogenous culture conditions. So we defined effects of agitation in bioreactor and figured out an optimum condition. After that scale-up studies were carried out with manufacturing-scale bioreactor based on these results. The results in terms of growth rate, viability cytotoxicity and purity, were comparable with lab-scale

Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin

AbstractEndothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp–EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage

Real-time interactive digital healthcare system for post-operative breast cancer patients: study protocol for a randomized controlled trial

Background After receiving breast cancer surgery or reconstruction, shoulder dysfunctions including weakness, post-operative pain, shoulder joint instability, and limited range of motion (ROM) often occur. Due to limited ROM, patients may suffer difficulty in activities of daily living, and quality of life may be reduced. The objective of this study is to compare the effects on shoulder ROM of a real-time interactive digital healthcare system and brochure-based home rehabilitation program in post-operative breast cancer patients. Methods This study is a prospective, multi-center, assessor-blinded randomized controlled trial. The study aims to recruit 100 breast cancer patients exhibiting limited shoulder ROM after undergoing axillary lymph node dissection or breast reconstruction following mastectomy. Patients will be randomly assigned to two groups for 8 weeks of rehabilitation: a digital healthcare system rehabilitation (intervention) group and a brochure-based rehabilitation (control) group. The primary outcome is the change in ROM of the affected shoulder between baseline and 12 weeks after enrollment. Secondary outcomes include pain in the affected shoulder, as measured using a numerical rating scale, functional outcomes (QuickDASH scores), and quality of life (FACT-B and EQ-5D-5L scores), all of which will be measured on enrollment and 4, 8, and 12 weeks thereafter. Discussion This study will compare the effectiveness of a newly developed, augmented reality-based real-time interactive digital healthcare system with that of brochure-based home rehabilitation for improving the shoulder ROM, pain, functional outcomes, and quality of life of post-operative breast cancer patients. Trial registration ClinicalTrials.gov NCT04316156 . Registered on 20 March 2020.This study is being financially supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0781)

Hand-Foot Syndrome with Scleroderma-like Change Induced by the Oral Capecitabine: A Case Report

Hand-foot syndrome (HFS) is a well-known adverse event associated with capecitabine, a prodrug of 5-Fluorouracil (5-FU). HFS manifests as acral erythema, with swelling and dysesthesia of the palms and plantar aspects of the feet, which in the absence of dosage reduction or drug cessation, progresses to moist desquamation and ulceration, resulting in serious infections and loss of function. We report a case of HFS, with scleroderma-like changes, apparently induced by capecitabine. In our case, capecitabine, given in the recommended dosage was observed to lead to hyperpigmentation of the palms and soles, followed by a distinct keratoderma-like thickening unfamiliar to usual cases of HFS. This case may provide important clues for revising the definition of HFS, and allow the formation of effective preventive strategies for this side effect of chemotherapy

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.

Pregnancy-related knowledge, risk perception, and reproductive decision making of women with epilepsy in Korea

AbstractPurposeTo determine the influence of pregnancy-related knowledge and the risk perception on reproductive decision making in women with epilepsy.MethodsWe enrolled women with epilepsy, who were of reproductive age and were considering having children in the future. A questionnaire was used to assess the level of pregnancy-related knowledge, perception of the offspring's risk for developing epilepsy or for having a congenial anomaly, and discussion with a physician concerning pregnancy-related issues. We evaluated the following outcome variables: (1) the decision to discontinue anti-epileptic drug (AED) during a future pregnancy regardless of the medical indication; and (2) the decision to have fewer children because of epilepsy.ResultsWe enrolled a total of 186 women with epilepsy. (1) Fifty-eight percent of the women were considering discontinuing AED during a future pregnancy regardless of the medical indication, and 25% of the women decided to have fewer children because of epilepsy. (2) The decision to discontinue AED during a future pregnancy was associated with low-level pregnancy-related knowledge. (3) The decision to have fewer children because of epilepsy was associated with an exaggerated perception of the offspring's risk for developing epilepsy. (4) The women who had ever discussed pregnancy-related issues with their physician were less likely to decide to discontinue AED during a future pregnancy; however, a discussion on this issue had no impact on their decision to have fewer children because of epilepsy.ConclusionMore than 50% of the women would decide to discontinue AED during a future pregnancy, and 25% of the women stated that they would have fewer children because of epilepsy. These data highlight the importance of education on pregnancy-related issues and genetic risk counseling