Factors of Hospital Ethical Climate among Hospital Nurses in Korea: A Systematic Review and Meta-Analysis.

In the current healthcare landscape, nurses frequently encounter various ethical dilemmas, necessitating situation-specific ethical judgments. It is crucial to thoroughly understand the factors that shape the hospital ethical climate and the elements that are influenced by this climate. This study aims to identify the variables associated with the hospital ethical climate perceived by Korean nurses. A literature search was conducted using the core database, and the effect sizes of relevant variables were analyzed using a comprehensive meta-analysis. The overall effect size analysis incorporated 56 variables, and a meta-analysis was performed on 7 variables. This study found correlations between ethical sensitivity (ESr = 0.48), moral distress (ESr = -0.30), empathy (ESr = 0.27), ethical leadership (ESr = 0.72), job satisfaction (ESr = 0.64), and intention to leave (ESr = -0.34) with the hospital ethical climate. Both personal and organizational attributes were moderately related to the hospital ethical climate. Enhancing the hospital ethical climate could positively affect both individuals and the organization. The protocol for this study has been registered with PROSPERO (CRD42022379812).

Effects of poly (ADP-ribose) polymerase inhibitor treatment on the repair process of ischemic acute kidney injury.

Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia-reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.

Factors of hospital ethical climate among hospital nurses in Korea: a protocol for systematic review and meta-analysis.

INTRODUCTION: The hospital ethical climate refers to the ethical work environment within a hospital, which may positively or negatively impact individual nurses, nursing organisations and patient care. Most of studies investigating the hospital ethical climate among Korean nurses have been published in Korean. However, papers addressing the hospital ethical climate in Korean were excluded from the systematic review. To enhance our comprehension of the hospital ethical climate, a systematic review specifically focusing on Korean nurses is imperative. Additionally, it is crucial to ascertain the factors associated with the hospital ethical climate and their respective effect sizes through meta-analyses. METHODS AND ANALYSIS: The systematic search will be conducted for papers published in both Korean and English, encompassing the hospital ethics climate of Korean nurses from 10 database inception to May 2023. Two reviewers will independently review each article based on the inclusion and exclusion criteria, and any differences in opinion will be resolved through discussion and consensus. The study selection process will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Quality assessment will be conducted using the Checklist for Analytical Cross-Sectional Studies provided by Joanna Briggs Institute. Effect size will be analysed using Comprehensive Meta-Analysis software V.2.0. The results of this study will identify factors related to the hospital ethical climate and the effect size of these factors among nurses in Korea. ETHICS AND DISSEMINATION: Ethical approval is not required, as the data will be collected from existing literature. Findings will be disseminated through peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022379812.

Three-dimensional evaluation of dentopalatal changes after rapid maxillary expansion in growing children.

INTRODUCTION: In growing children with transverse malocclusion problems, various types of rapid maxillary expanders (RMEs) have been effectively used in skeletal and dental expansions. We evaluated 3-dimensional dentopalatal changes in growing children who underwent maxillary expansion using RMEs and bonded RMEs. METHODS: We investigated dentopalatal changes in 20 patients treated with bonded RMEs, 19 with RMEs, and 38 control patients. Dental plaster models before and after expansion were scanned 3-dimensionally and superimposed to evaluate transverse expansion, expansion ratio, angular expansion, and palatal expansion height ratio. RESULTS: Using bonded RMEs, similar anterior and posterior dental expansions were achieved with an efficiency of 69%-76% (expansion ratio), and palatal soft-tissue expansion occurred more apically in the posterior area (palatal expansion height ratio, 1.00) than in the anterior area (palatal expansion height ratio, 0.64). Using RMEs, a larger posterior dental expansion was achieved, with an efficiency of 106%-117% (expansion ratio), than anterior dental expansion (55%-60%), and palatal soft-tissue expansion occurred more apically in the posterior area (palatal expansion height ratio, 0.99) than anterior area (palatal expansion height ratio, 0.23). CONCLUSIONS: Dental expansions in the anterior and posterior areas were similar using bonded RMEs, whereas the posterior dental expansions were larger than those of the anterior area using RMEs. The entire palatal soft-tissue slope expanded in the posterior area, whereas the occlusal part expanded in the anterior area using RMEs and bonded RMEs.

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells.

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways.

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3ß, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

Prognostic significance of albuminuria in elderly of various ages with diabetes.

It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65-69, 70-74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P < 0.001 for all), and the all-cause mortality was 13.1%, 27.4%, and 31.7% (P < 0.001 for A1 vs A2, P < 0.001 for A1 vs A3), respectively. Albuminuria stages were independently associated with an increased risk of ESKD [fully adjusted hazard ratios (HR): 3.650 (1.987-6.702) for A2, 10.404 (5.706-18.972) for A3 vs. A1]. The HRs of all-cause mortality were 1.742 (1.411-2.153) for A2 and 1.810 (1.344-2.441) for A3. The associations between albuminuria stages and the risk of ESKD and all-cause mortality were consistent across all age groups. Even microalbuminuria is also a risk factor for incident ESKD and mortality in elderly patients with diabetes.

3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases.

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Licochalcone B Induces ROS-Dependent Apoptosis in Oxaliplatin-Resistant Colorectal Cancer Cells via p38/JNK MAPK Signaling.

Licochalcone B (LCB) exhibits anticancer activity in oral cancer, lung cancer, and hepatocellular carcinoma cells. However, little is known about its antitumor mechanisms in human oxaliplatin-sensitive and -resistant colorectal cancer (CRC) cells. The purpose of the present study was to investigate the antitumor potential of LCB against human colorectal cancer in vitro and analyze its molecular mechanism of action. The viability of CRC cell lines was evaluated using the MTT assay. Flow cytometric analyses were performed to investigate the effects of LCB on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. The results demonstrated that LCB induced a reduction in cell viability, apoptosis, G2/M cell cycle arrest, ROS generation, MMP depolarization, activation of multi-caspase, and JNK/p38 MAPK. However, p38 (SB203580) and JNK (SP600125) inhibitors prevented the LCB-induced reduction in cell viability. The ROS scavenger N-acetylcysteine (NAC) inhibited LCB-induced reduction in cell viability, apoptosis, cell cycle arrest, ROS generation, MMP depolarization, and multi-caspase and JNK/p38 MAPK activities. Taken together, LCB has a potential therapeutic effect against CRC cells through the ROS-mediated JNK/p38 MAPK signaling pathway. Therefore, we expect LCB to have promising potential as an anticancer therapeutic and prophylactic agent.

The impact of preoperative kidney replacement therapy on kidney outcome and survival in patients with left ventricular assist device.

Left ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (ß -0.94, p < 0.01), preexisting chronic kidney disease (ß -21.89, p < 0.01), and high serum creatinine (ß -13.95, p < 0.01) were identified as independent predictors of post-LVAD eGFR decline. Mortality rate was higher, and more patients progressed to end-stage kidney disease in KRT group than control group. However, LVAD still can be considered as the treatment option in end-stage HF patients with severe CRS requiring KRT, especially in those with young age and previous normal kidney function.

Acute kidney injury in bortezomib-treated patients with multiple myeloma.

BACKGROUND: The nephrotoxicity of bortezomib, a proteasome inhibitor, has not yet been elucidated, although tumor lysis syndrome (TLS) associated with multiple myeloma (MM) has been reported to increase after introduction of the drug. This study compared the incidence and risk factors for acute kidney injury (AKI) and TLS in patients with MM after bortezomib-based chemotherapy to investigate drug-related nephrotoxicity. METHODS: From 2006 to 2017, 276 patients who underwent a first cycle of bortezomib-based chemotherapy for MM were identified in a single tertiary hospital. Laboratory TLS was defined according to the Cairo-Bishop definition. Development of AKI was assessed by AKI Network criteria within 7 days of the first chemotherapy. RESULTS: The median (interquartile range) age was 65 (56-72) years, and baseline estimated glomerular filtration rate (eGFR) was 61.3 (34.1-89.1) mL/min/1.73 m2. The incidences of AKI and laboratory TLS were 17% (n = 47) and 13% (n = 36), respectively. Ten (3.6%) subjects met both AKI and TLS criteria. Multivariate analyses showed that lower eGFR category [30-59, odds ratio (OR) 3.005 (95% confidence interval 1.163-7.976); 15-29, OR 4.225 (1.183-15.000); <15, OR 16.154 (3.831-70.920) vs ≥60, P < .001], lower serum albumin level [per 1 increase, OR 0.479 (0.256-0.871), P = .018], renal amyloidosis [OR 13.039 (4.108-44.041), P < .001] and use of acyclovir during bortezomib treatment [OR 3.689 (1.133-14.469), P = .042] were predictors of AKI. MM stages and ß-2-microglobulin were not associated with increased risk of AKI. Regarding laboratory TLS, MM stage and ß-2-microglobulin were higher in those with TLS than in others. In multivariate analyses, ß-2-microglobulin level [OR 1.204 (1.005-1.461), P = .038] and absence of high-risk chromosome abnormalities [OR 0.143 (0.022-0.588), P = .016] were associated with higher risk of TLS. CONCLUSIONS: Development of AKI was often observed in the absence of TLS in patients with MM after treatment with bortezomib. In addition, the risk factors for AKI and TLS varied widely. These findings indicate the potential nephrotoxicity of bortezomib irrespective of TLS in patients with decreased kidney function.

Ramal inclination in the frontal plane after bimaxillary orthognathic surgery in skeletal class III facial asymmetry : Spontaneous changes and stability.

PURPOSE: This study aimed to observe spontaneous changes of ramal inclination in the frontal plane (FRI) and its stability in skeletal class III asymmetry patients corrected with bimaxillary surgery. The correlation between FRI change and surgical skeletal change was also investigated. METHODS: Forty-nine patients with skeletal class III facial asymmetry who underwent orthognathic surgery with at least 1° change in FRI after surgery were analyzed. FRI and other factors were measured on frontal and lateral cephalograms before surgery (T1), after surgery (T2), and at follow-up after at least 6 months (T3). Correlation analysis was performed to determine pre- and postoperative factors associated with FRI change and stability. RESULTS: FRI increased significantly on the deviated side and decreased on the nondeviated side after surgery. The FRI changes remained stable during follow-up. No correlation between FRI changes and skeletal changes during surgery were found except between the change of FRI during follow-up (T3-T2) and mandibular setback amount (T2-T1), with a weak coefficient of 0.32. CONCLUSION: The FRI changes after bimaxillary orthognathic surgery in skeletal class III asymmetry reduced the FRI difference between the deviated and nondeviated side and remained stable for at least 6 months after surgery. No clinically significant correlation was found between measured skeletal changes during surgery and FRI changes.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET.

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Echinatin induces reactive oxygen species-mediated apoptosis via JNK/p38 MAPK signaling pathway in colorectal cancer cells.

Colorectal cancer (CRC) is a very common and deadly cancer worldwide, and oxaliplatin is used as first-line chemotherapy. However, resistance usually develops, limiting treatment. Echinatin (Ech) is the main component of licorice and exhibits various therapeutic effects on inflammation-mediated diseases and cancer, ischemia/reperfusion, and liver injuries. The present study elucidated the underlying molecular mechanism of Ech-induced apoptosis in both oxaliplatin-sensitive (HT116 and HT29) and -resistant (HCT116-OxR and HT29-OxR) CRC cells. To evaluate the antiproliferative activities of Ech, we performed MTT and soft agar assays. Ech reduced viability, colony size, and numbers of CRC cells. The underlying molecular mechanisms were explored by various flow cytometry analyses. Ech-induced annexin-V stained cells, reactive oxygen species (ROS) generation, cell cycle arrest, JNK/p38 MAPK activation, endoplasmic reticulum (ER) stress, mitochondrial membrane potential depolarization, and multi-caspase activity. In addition apoptosis-, cell cycle-, and ER stress-related protein levels were confirmed by western blotting. Moreover, we verified ROS-mediated cell death by treatment with inhibitors such as N-acetyl-L-cysteine, SP600125, and SB203580. Taken together, Ech exhibits anticancer activity in oxaliplatin-sensitive and -resistant CRCs by inducing ROS-mediated apoptosis through the JNK/p38 MAPK signaling pathway. This is the first study to show that Ech has the potential to treat drug-resistant CRC, providing new directions for therapeutic strategies targeting drug-resistant CRC.

Impact of protocolized fluid management on electrolyte stability in patients undergoing continuous renal replacement therapy.

Objective: Continuous renal replacement therapy (CRRT) is the standard treatment for critically ill patients with acute kidney injury (AKI). Electrolyte disturbance such as hypokalemia or hypophosphatemia occurs paradoxically in patients undergoing CRRT due to high clearance. We developed a fluid management protocol for dialysate and replacement fluid that depends on serum electrolytes and focuses on potassium and phosphate levels to prevent electrolyte disturbance during CRRT. The impact of our new fluid protocol on electrolyte stability was evaluated. Methods: Adult patients who received CRRT between 2013 and 2017 were included. Patients treated 2 years before (2013-2014; pre-protocol group) and 2 years following development of the fluid protocol (2016-2017; protocol group) were compared. The primary outcomes were individual coefficient of variation (CV) and abnormal event rates of serum phosphate and potassium. Secondary outcomes were frequency of electrolyte replacement and incidence of cardiac arrhythmias. Individual CV and abnormal event rates for each electrolyte were analyzed using the Wilcoxon rank-sum test and Chi-square test with Yates' continuity correction. Results: A total of 1,448 patients was included. Both serum phosphate and potassium were higher in the protocol group. The CVs of serum phosphate (pre-protocol vs. protocol, 0.275 [0.207-0.358] vs. 0.229 [0.169-0.304], p < 0.01) and potassium (0.104 [0.081-0.135] vs. 0.085 [0.064-0.110], p < 0.01) were significantly lower in the protocol group. The abnormal event rates of serum phosphate (rate [95% CI], 0.410 [0.400-0.415] vs. 0.280 [0.273-0.286], p < 0.01) and potassium (0.205 [0.199-0.211] vs. 0.083 [0.079-0.087], p < 0.01) were also significantly lower in the protocol group. Conclusion: The protocolized management of fluid in CRRT effectively prevented hypophosphatemia and hypokalemia by inducing excellent stability of serum phosphate and potassium levels.

Clinical relevance of postoperative proteinuria for prediction of early renal outcomes after kidney transplantation.

BACKGROUND: Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. METHODS: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2-3 weeks postoperatively), and 3-6 months postoperatively. RESULTS: The median age of the patients was 51 years (interquartile range, 43-59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. CONCLUSION: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

Deoxypodophyllotoxin Induces ROS-Mediated Apoptosis by Modulating the PI3K/AKT and p38 MAPK-Dependent Signaling in Oral Squamous Cell Carcinoma.

Deoxypodophyllotoxin (DPT), a naturally occurring flavonolignan, possesses several pharmacological properties, including anticancer property. However, the mechanisms underlying DPT mode of action in oral squamous cell carcinoma (OSCC) remain unknown. This study aimed to investigate the anticancer effects of DPT on OSCC and the underlying mechanisms. Results of the MTT assay revealed that DPT significantly reduced the cell viability in a time- and dose-dependent manner. Flow cytometry analysis revealed that DPT induces apoptosis in OSCC cells in a dose-dependent manner. Moreover, DPT enhanced the production of mitochondrial reactive oxygen species (ROS) in OSCC cells. Mechanistically, DPT induced apoptosis in OSCC cells by suppressing the PI3K/AKT signaling pathway while activating the p38 MAPK signaling to regulate the expression of apoptotic proteins. Treatment with SC79, an AKT activator, reversed the effects of DPT on AKT signaling in OSCC cells. Taken together, these results provide the basis for the use of DPT in combination with conventional chemotherapy for the treatment of oral cancer.

Isolinderalactone sensitizes oxaliplatin-resistance colorectal cancer cells through JNK/p38 MAPK signaling pathways.

BACKGROUND: Isolinderalactone (ILL), a sesquiterpene lactone compound, can be extracted from the root of Lindera aggregate. Physiological activities of ILL, including anti-inflammatory and anti-proliferative effects, have been investigated in multiple diseases. Nevertheless, little is known regarding its anti-cancer activities and the mechanism of action of ILL in targeting human CRC cells. PURPOSE: To determine ILL-mediated anti-proliferative effects on oxaliplatin (Ox)-sensitive and resistant colorectal cancer (CRC) cells and underlying mechanisms involved in its effects focusing on signal transduction. METHODS: Inhibitory effect of ILL on CRC cells was evaluated by analyzing mitochondrial membrane potential (MMP) dysfunction and multi-caspase activity. Apoptosis-regulating proteins and JNK/p38 signaling molecules were monitored by Western blotting. ROS-dependent physiological modifications by ILL were confirmed by pretreatment with N-acetylcysteine (NAC). Moreover, the involvement of JNK/p38 signaling in ROS-mediated apoptosis was verified by treatment with SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor). RESULTS: ILL decreased cell viability and colony formation in both CRC Ox-sensitive (HCT116 and HT29) and Ox-resistant (OxR) (HCT116-OxR and HT29-OxR) cells. ILL induced G2/M phase cell cycle arrest, ROS generation, phosphorylated (p)JNK/p38 MAPK activation, mitochondrial membrane potential (MMP) depolarization, and multi-caspase activation, which eventually triggered apoptotic cell death of CRC cells. In addition, combined treatment with ILL and SP600125, SB203580, or pan-caspase inhibitor (Z-VAD-FMK) prevented decreases in cell viability seen after treatment with ILL alone. Pretreatment with NAC attenuated ILL-mediated apoptosis, ROS production, and p-JNK/p38 expression. CONCLUSION: Taken together, our results suggest that ILL can exert its anticancer effect in CRC Ox-sensitive and OxR cells by inducing ROS-mediated apoptosis through JNK/p38 MAPK signaling pathways. This is the first study demonstrating that ILL has a potential to improve drug efficacy against resistance mechanisms, providing a new insight into therapeutic strategies targeting drug-resistant CRC.