First Organ Donation after Circulatory Death Following Withdrawal of Life-sustaining Treatment in Korea: a Case Report.

In February 2018, the Withdrawal of the Life-sustaining Treatment (WLST) Decision Act was legalized in Korea. Donation after circulatory death (DCD) after WLST was classified as DCD category III. We report the first case of successful organ donation after WLST in Korea. A 52-year-old male who experienced cerebral hemorrhage was a potential brain-dead donor with donation consent. During the first brain death examination, Babinski reflex was present, which disappeared two days later. Then, electroencephalography was performed five times at intervals of 2 to 3 days, according to the recommendation of a neurologist. The patient was transferred to the OR at 19:30 July 3, 2020. At 20:00, an intensive care unit specialist performed extubation and discontinued vasopressors. Oxygen saturation fell to < 70% in 1 minute, which signaled the beginning of functional warm ischemia. At 20:15, asystole was confirmed; after 5 minutes of "no-touch time," circulatory death was declared. Organ procurement surgery was initiated, with surgeons performing the recipient surgery ready in the adjacent OR. Through the first successful DCD case, we expected that DCD will be actively implemented in Korea, saving the lives of patient waiting for transplantation and resolving the imbalance between organ receipt and donation.

Organ donation from brain-dead pediatric donors in Korea: A 5-year data analysis (2013-2017).

In Korea, 2-4% of brain-dead organ donations are from donors <16 years of age. We aimed to identify the current status of and challenges in pediatric organ donation from brain-dead donors in Korea. We performed a retrospective analysis using data from KONOS between January 1, 2013, and December 31, 2017. Our research identified 107 pediatric donors aged <16 years, representing 4.4% of all donors in Korea between 2013 and 2017. The consent rate was higher in PDs than in adult donors (47.0% vs 44.9%). The most common cause of brain death in PDs was hypoxia (28.0%), followed by brain tumor and trauma, whereas that in ADs was brain hemorrhage/stroke (42.4%), followed by trauma and hypoxia (P < .001). In both groups, the kidney (PDs vs ADs: 75.7% vs 88.5%), liver (58.9% vs 46.2%), and heart (32.7% vs 29.7%) were the organs most commonly transplanted. However, pancreatic (PDs vs ADs: 30.0% vs 11.7%, P < .001) and small bowel transplantations (4.7% vs 0.2%, P < .001) were more common in PDs, whereas lung (7.5% vs 14.5%, P = .046) and corneal transplantations (14.0% vs 36.2%) were more common in ADs. Only a small proportion of organ donations in Korea are from PDs, but this rate has been maintained. Given the current status of brain-dead pediatric organ donation, a more active approach is required to bring about improvement.

Role of antimicrobial peptides expressed by host cells upon infection by Helicobacter pylori.

Colonization of the stomach by Helicobacter pylori can result in such gastrointestinal illnesses as chronic gastritis, peptic ulcer and gastric cancer. Antimicrobial peptides (AMPs) are expressed in the stomach and play a key role in the innate immune responses to H. pylori in humans. During H. pylori infections, AMP expression mediated by NOD-1, NF-kB and/or ERK, functions to eradicate the bacteria, thereby preventing the gastritis and gastric cancer. This suggests that the use of synthetic AMPs could be one component of an effective therapeutic strategy to combat H. pylori. In addition, it appears that some peptides, and combinations of peptides, act synergistically with conventional drugs, thereby enhancing therapeutic efficacy. Our aim in this article was to review what is currently known about gastric AMP expression in response to H. pylori infection, and to briefly discuss the potential use of AMPs, either alone or in combination with conventional antibiotics, for the treatment of H. pylori infection.

FERM domain promotes resveratrol-induced apoptosis in endothelial cells via inhibition of NO production.

Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 µM resveratrol, whereas FERM had no effect on apoptosis induced by TNF-α. We determined that resveratrol at low doses (<20 µM) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production.

Pinosylvin induces cell survival, migration and anti-adhesiveness of endothelial cells via nitric oxide production.

Pinosylvin is a phenolic compound mainly found in the Pinus species. To determine the vascular functions of pinosylvin, we first examined both proliferation and apoptosis of bovine aortic endothelial cells (BAECs) in the presence of pinosylvin. When BAECs were treated with pinosylvin, etoposide- or starvation-induced apoptosis was shown to be significantly reduced. The anti-apoptotic effect of pinosylvin was mediated by inhibition of caspase-3. Moreover, pinosylvin was shown to activate endothelial nitric oxide synthetase (eNOS). At 1 pM, pinosylvin appeared to have a cell-proliferative effect in the endothelial cell. The pinosylvin-induced cell proliferation was declined by treatment with L-NAME, an eNOS inhibitor. Then, we found that pinosylvin had a stimulatory effect on cell migration and tube formation. These stimulatory effects suggest that pinosylvin is likely to act as a pro-angiogenic factor. Yet another effect of pinosylvin was inhibition of lipopolysaccharide-induced THP-1 cell adhesion to endothelial cells. Altogether, we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases.

Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced beta-cell damage by inhibiting NF-kappaB.

AIM: To clarify the mechanism underlying the anti-diabetic activities of cortex cinnamomi extract (CCE). METHODS: To induce in vivo diabetes, mice were injected with streptozotocin (STZ) via a tail vein (100 mg STZ/kg body weight). To determine the effects of CCE, mice were administered CCE twice daily for 7 d by oral gavage starting 1 wk before the STZ injection. Blood glucose and plasma insulin concentration were measured as an index of diabetes. Also, to induce cytotoxicity of RINm5F cells, we treated with cytokines (IL-1beta (2.0 ng/mL) and IFN-gamma (100 U/mL)). Cell viability and nitric oxide production were measured colorimetrically. Inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. The activation of NF-kappaB was assayed by using gel mobility shift assays of nuclear extracts. RESULTS: Treatment of mice with STZ resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of STZ were completely prevented when mice were pretreated with CCE. The inhibitory effect of CCE on STZ-induced hyperglycemia was mediated through the suppression of iNOS expression. In rat insulinoma RINm5F cells, CCE completely protected against interleukin-1beta and interferon-gamma-mediated cytotoxicity. Moreover, RINm5F cells incubated with CCE showed significant reductions in interleukin-1beta and interferon-gamma-induced nitric oxide production and in iNOS mRNA and protein expression, and these findings correlated well with in vivo observations. CONCLUSION: The molecular mechanism by which CCE inhibits iNOS gene expression appears to involve the inhibition of NF-kappaB activation. These results reveal the possible therapeutic value of CCE for the prevention of diabetes mellitus progression.

Molecular mechanisms of apoptosis induced by Scorpio water extract in human hepatoma HepG2 cells.

AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells were incubated with various concentrations of SWE. After 24-h incubation, cytotoxicity and apoptosis evaluations were determined by MTT and DNA fragmentation assay, respectively. After treatment with SWE, mitochondrial membrane potential (MMP) was determined by measuring the retention of the dye 3,3'-dihexyloxacarbocyanine (DiOC(6)(3)) and the protein expression including cytochrome C and poly-(ADP-ribose) polymerase (PARP) were measured by Western blotting. Caspase-3 and -9 enzyme activities were measured using specific fluorescence dyes such as Ac-DEVD-AFC and Ac-LEHD-AFC. RESULTS: We found that treatment with SWE induced apoptosis as confirmed by discontinuous DNA fragmentation in cultured human hepatoma HepG2 cells. Our investigation also showed that SWE-induced apoptosis of HepG2 cells were associated with intracellular events including disruption of MMP, increased translocation of cytochrome C from mitochondria to cytosol, activation of caspase-3, and PARP. Pre-treatment of N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), a caspase-3 specific inhibitor, or cyclosporin A (CsA), an inhibitor of MMP disruption, completely abolished SWE-induced DNA fragmentation. CONCLUSION: These results suggest that SWE possibly causes mitochondrial damage, leading to cytochrome C release into cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic cell death in HepG2 cells. These results further suggest that Scorpio may be a valuable agent of therapeutic intervention of human hepatomas.