The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

Relationship between Arachidonate 5-Lipoxygenase-Activating Protein Gene and Peripheral Arterial Disease in Elderly Patients Undergoing General Surgery: A Retrospective Observational Study.

Patients with peripheral arterial disease (PAD) are at a higher risk of developing postoperative complications. Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays an important role in atherosclerosis pathogenesis. In this study, the relationship between PAD and several single nucleotide polymorphisms (SNPs) of ALOX5AP (rs17216473, rs10507391, rs4769874, rs9551963, rs17222814, and rs7222842) was investigated in elderly patients undergoing general surgery. The medical records of 129 patients aged > 55 years who underwent elective general surgery between May 2018 and August 2019 were retrospectively reviewed. The A/A in rs17216473, A/A in rs10507391, G/G in rs4769874, and A/A in rs9551963 were calculated as 0 points and the rest as 1 point to define the genetic risk score. The prevalence of PAD tended to increase with higher genetic risk scores (patients had less ALOX5AP gene polymorphism of A/A in rs17216473, A/A in rs10507391, G/G in rs4769874, or A/A in rs9551963) (p = 0.005). Multivariate logistic regression analysis revealed that the genetic risk score (p = 0.009) and age (p = 0.007) were positively correlated with the prevalence of PAD. Genetic polymorphisms of ALOX5AP and age were associated with the prevalence of PAD in this study.

Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner: pilot study.

PURPOSE: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse during sleep, which induces chronic intermittent hypoxia (CIH). CIH results in low-grade inflammation, sympathetic overactivity, and oxidative stress. Nevertheless, it remains unclear how exposure to CIH affects olfaction. The purpose of this study was, therefore, to investigate the cytotoxic effects of CIH exposure on mouse olfactory epithelium and the underlying pathophysiology involved. METHODS: Mice were randomly divided into four groups: Youth mouse (You) + room air (RA), You + intermittent hypoxia (IH), Elderly mouse (Eld) + RA, and Eld + IH (n = 6 mice/group). Mice in the two hypoxia groups were exposed to CIH. The control condition involved exposure to room air (RA) for 4 weeks. Olfactory neuroepithelium was harvested for histologic examination, gene ontology analysis, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. RESULTS: Based on qRT-PCR analysis, olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL mRNA levels were lower, whereas NGFR, CNPase, NGFRAP1, NeuN, and MAP-2 mRNA levels were higher in the You + IH group than in the You + RA group. Olfactory receptor-regulated genes, neurogenesis-related genes and immunohistochemical results were altered in nasal neuroepithelium under CIH exposure. CONCLUSIONS: Based on genetic and cytologic analysis, CIH impacted the olfactory neuroepithelium in an age-dependent manner. Our findings suggest that CIH-induced damage to the olfactory neuroepithelium may induce more severe change in the youth than in the elderly.

Risk factors for heel pressure injury in cardiovascular intensive care unit patients.

This study analyzed the risk factors for heel pressure injury in cardiovascular intensive care unit patients with the aim of laying the groundwork for preventive nursing interventions. We conducted a retrospective case-control study of 92 patients who were admitted to the cardiovascular surgical or medical intensive care unit of a university hospital in South Korea between January and December 2017. Of these patients, 31 and 61 were included to the heel pressure injury group and the non-heel pressure injury group, respectively. Data on their demographic, disease-related, and intensive care unit treatment characteristics, as well as the degree of pressure injury, were collected from the hospital's electronic medical records using a standardized form. Cardiac surgery (P < .001), operation time (P = .001), use of a mechanical ventilator (P < .001), use of vasoconstrictors (P < .001), use of sedative drugs (P < .001), and extracorporeal membrane oxygenation treatment (P < .001) were identified as significant risk factors for heel pressure injury. A total of 22 patients (71%) from the heel pressure injury group developed deep tissue injury, and 16 patients (51.6%) who received extracorporeal membrane oxygenation treatment developed heel pressure injury.

Expanded Efficacy of Venovenous Extracorporeal Membrane Oxygenation Support for Deceased Donor Liver Transplantation.

BACKGROUND: Perioperative respiratory failure occurs frequently in liver transplantation (LT) recipients. Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been applied in patients with acute and potentially reversible life-threatening respiratory failure that is unresponsive to conventional therapies. VV-ECMO is used as a bridging device for lung transplantation. However, there are few reports on VV-ECMO as bridging therapy in LT patients with respiratory failure. This study assessed patient outcomes of VV-ECMO after LT and investigated its applicability and safety in LT surgery. METHODS: From January 2017 to May 2019, VV-ECMO was applied in 8 deceased donor LT patients at Pusan National University Yangsan Hospital. RESULTS: Patients administered pre- or postoperative VV-ECMO showed a 50% 1-year survival rate and 75% success rate for ECMO weaning. Six patients were administered preoperative VV-ECMO for respiratory failure, of whom 4 patients survived for longer than a year. Two patients who received VV-ECMO for refractory hypoxia during LT died; 1 failed ECMO weaning, and the other was successfully weaned off ECMO but died of other causes. CONCLUSION: VV-ECMO could lower the risk of hypoxemia-related organ failure while awaiting and during LT via better controlled gas exchange without significant acute morbidity. VV-ECMO may expand operability in patients with severe respiratory failure awaiting LT.

Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-II collagen-induced arthritis.

OBJECTIVE: SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA). METHODS: In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3. RESULTS: Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1ß, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3. CONCLUSION: These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.

The effect of dexmedetomidine and midazolam on combined spinal-epidural anesthesia in patients undergoing total knee arthroplasty.

BACKGROUND: Intravenous dexmedetomidine has been reported to potentiate the anesthetic effect of local anesthetics and improve the quality of postoperative analgesia when used as an adjuvant in neuraxial block. We compared the effects of intravenous dexmedetomidine and midazolam for sedation on combined spinal-epidural (CSE) anesthesia. METHODS: This study included 50 patients undergoing total knee arthroplasty. CSE anesthesia was given using 10 mg bupivacaine for all patients. After checking the maximum sensory and motor levels, the patients were randomly allocated into two groups of 25 each to receive intravenous continuous infusion of dexmedetomidine (Group D) or midazolam (Group M) for sedation during surgery. Regression block level, hemodynamic changes, and sedation score were compared between the groups when the patients entered the postanesthetic care unit (PACU). For patient-controlled epidural analgesia, 0.2% levobupivacaine with 650 µg of fentanyl (150 ml in total) was infused at a rate of 1 ml/h, in addition to a 3-ml bolus dose with a 30-min lockout time. The visual analogue scale scores, additional analgesic demand, patient satisfaction, and adverse events between the two groups were also compared postoperatively. RESULTS: A significant difference was observed in relation to the sensory block level in the PACU (Group D: 6.3 ± 2.1; Group M: 3.2 ± 1.9) (P = 0.002). The motor block level and other outcomes showed no significant intergroup differences. CONCLUSIONS: Intravenous injection of dexmedetomidine, rather than midazolam, for procedural sedation is associated with prolonged sensory block, with comparable incidences of adverse events during CSE anesthesia.

Effect of anesthetic method on incidence of delirium after total hip replacement arthroplasty in South Korea: a population-based study using National Health Insurance claims data.

BACKGROUND: There are various reports on the effects of the anesthetic method on neurologic complications. A population-based study was conducted to estimate the effect of anesthetic method on the incidence of postoperative delirium in patients that underwent total hip replacement arthroplasty in South Korea. METHODS: The Korean National Health Insurance claims database was used to retrospectively identify and analyze 24,379 cases of total hip replacement arthroplasty, defined as patients having a claim record with the operation code 'N0711,' from January 2008 to December 2017. Patients were divided into two groups, a general anesthesia group (n = 9,921) and a regional anesthesia group (n = 14,458). The incidence of delirium was assessed in cases when patients used medications for delirium, such as haloperidol, chlorpromazine, olanzapine, and risperidone. RESULTS: Of the 9,921 patients receiving general anesthesia and 14,458 receiving regional anesthesia, 142 (1.43%) and 209 (0.86%) experienced postoperative delirium after total hip replacement arthroplasty, respectively. There was no significant difference between the groups (P = 0.92). In logistic regression analysis, sex (P = 0.038) and patients with acquired immune deficiency syndrome (P = 0.008) were predictors of postoperative delirium. CONCLUSIONS: Our results revealed that the anesthetic method was not associated with the incidence of postoperative delirium. In addition, the results suggest that male patients and patients with acquired immune deficiency syndrome undergoing total hip replacement arthroplasty carefully managed for postoperative delirium after surgery.

Experience of operating an anesthesia preoperative evaluation clinic in South Korea: An observational study of surgeons' satisfaction.

The benefits of an anesthesia pre-operative evaluation clinic (APEC) based on outpatients are well described in previous literatures. In the majority of hospitals in South Korea, preoperative anesthetic evaluation for surgical patients is limited to hospitalized patients on the day before surgery. Thus, we would like to share our institutional experience of implementing an APEC based on outpatients and report on the attitudes and satisfaction of the medical staff (surgeons).A 2-page survey was distributed to all specialists and resident physicians involved in surgery at a single university hospital during a 3-month period. A 5-point Likert scale of agreement and an open-ended question examined perceptions of APEC. A total of 123 questionnaires were distributed and 67 surveys were collected over a 3-month period with a 54.5% collection rate. The surgeons' perceptions of APEC are summarized in . It is difficult to state the tendency of surgeons' perception of the clinic, including workload, patient satisfaction, patient safety, necessity, cost-effectiveness, and efficiency through this survey. However, many surgeons chose to comment on suggestions to improve the quality of the APEC through the open-ended question.The surgeons' attitude and satisfaction to anesthetic services including APEC are an important component of achieving quality improvement. Although it is difficult to state the tendency of surgeons' perception of the clinic, including workload, patient satisfaction, patient safety, necessity, cost-effectiveness, and efficiency through this survey, continuous assessment and feedback may improve efficiency of the APEC and affect patient perception as well.

The influence of rapid eye movement sleep deprivation on nociceptive transmission and the duration of facial allodynia in rats: a behavioral and Fos immunohistochemical study.

BACKGROUND: Disrupted sleep is associated with a reciprocal influence on headaches and is one of the contributing factors in the process of chronicity. The goal of the present study was to investigate the influence of sleep on headaches using animal rapid eye movement (REM) sleep deprivation and supradural capsaicin infusion models. METHOD: Sprague-Dawley rats underwent REM sleep deprivation (REMSD) for 96 h. The sensory threshold to mechanical stimuli, assessed by the von Frey monofilament test, was measured during the REMSD period. Additionally, the Fos protein expression level was measured in the trigeminocervical complex, periaqueductal gray, and hypothalamus. Following supradural infusion of capsaicin, we evaluated the duration of facial allodynia for 28 days after REMSD. RESULTS: After REMSD, the sensory threshold to mechanical stimuli was significantly decreased (p < 0.01) and Fos-positivity in the posterior (p = 0.010) and dorsomedial hypothalamus (p = 0.024), ventrolateral periaqueductal gray (p = 0.016), and superficial layer of the trigeminocervical complex (p = 0.019) were significantly increased. The duration of facial allodynia induced by supradural capsaicin infusion was significantly longer in the REM sleep deprivation and capsaicin infusion group (Day 10 PSD vs. Day 25 PSD). CONCLUSION: The present study demonstrates that REM sleep deprivation increased nociceptive transmission from trigeminal nerve endings. Furthermore, it suggests that sleep deprivation may contribute to the chronicity of facial allodynia.

A novel PI3K/mTOR dual inhibitor, CMG002, overcomes the chemoresistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of gynecologic-related mortality worldwide. Despite successful initial treatment, overall survival rates are very low because tumors develop resistance to chemotherapeutic drugs. The PI3K/mTOR pathway is a key signaling pathway involved in drug resistance of ovarian cancer cells. The aim of this study was to examine the effect of a newly developed PI3K/mTOR dual inhibitor, CMG002, on chemoresistant ovarian cancer cells. METHODS: We examined the effects of CMG002, and its synergistic effects when combined with paclitaxel or cisplatin, on cell viability, cell cycle arrest, and apoptosis of PTX-resistant SKpac17 or cisplatin-resistant A2780cis ovarian cancer cells in vitro. Western blot analysis was performed to assess expression of PI3K, p-mTOR, p-Akt, p-S6, Bim, and caspase-3. In vivo studies were carried out in a xenograft mouse model, followed by TUNEL and immunohistochemical staining of excised tumor tissue. RESULTS: CMG002 showed marked toxicity against chemoresistant ovarian cancer cells and re-sensitized these cells to chemotherapeutic agents by suppressing cell proliferation and inducing G1 cell cycle arrest and apoptosis. In vivo xenograft studies revealed that treatment with CMG002, either alone or in combination with paclitaxel or cisplatin, led to a marked reduction in tumor growth. CMG002 caused marked suppression of mTOR (Ser2448), Akt (Ser473), Akt (Thr308), and S6 (Ser235/236) phosphorylation, both in vitro and in vivo. CONCLUSION: Taken together, CMG002, a very potent PI3K/mTOR dual inhibitor, induced cytotoxicity in chemoresistant ovarian cancer cells, suggesting that this novel inhibitor might be a new therapeutic strategy for chemoresistant ovarian cancer.

Aqueous extract of Dipsacus asperoides suppresses lipopolysaccharide-stimulated inflammatory responses by inhibiting the ERK1/2 signaling pathway in RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci Radix, which is the dried root of Dipsacus asperoides C. Y. Cheng and T. M. Ai (Dipsacaceae), is used to treat back pain and blood stasis syndrome in Korean traditional medicine. AIM OF THE STUDY: To understand the mechanisms responsible for the pharmacological activities of D. asperoides, we investigated the inhibitory effect of D. asperoides on lipopolysaccharide (LPS)-induced inflammation in mouse macrophages RAW 264.7 cells. MATERIALS AND METHODS: Aqueous extract of D. asperoides (AEDA) was prepared by boiling D. asperoides in water and then administered to LPS treated RAW 264.7 cells. Cell viabilities were measured using an MTT assay, and protein levels were determined by western blotting. The ROS scavenging activity of AEDA was measured using a DCFH-DA assay and levels of nitric oxide (NO) were determined using a NO assay. The nuclear translocations of NF-κB and Nrf2 were investigated immunocytochemically, and pro-inflammatory cytokines in supernatant were evaluated by ELISA. RESULTS: Treatment with AEDA suppressed the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. AEDA also reduced ROS, pro-inflammatory cytokine (IL-6 and IL-1ß) levels, and iNOS-derived NO and COX-2-derived prostaglandin E2 release to medium, and suppressed the phosphorylation and degradation of IκB and the activation of NF-κB in macrophages. Furthermore, treatment with AEDA inhibited the ERK1/2 pathway but not the JNK or p38 MAPK pathways. In addition, AEDA significantly promoted Nrf2 translocation from cytoplasm to nucleus and up-regulated the expression of HO-1. CONCLUSION: These results suggest that AEDA has anti-inflammatory and anti-oxidative effects through the inhibition of NF-κB and ERK1/2 and the activation of Nrf2/HO-1 in macrophages.

Bloodless living donor liver transplantation: Risk factors, outcomes, and diagnostic predictors.

Massive bleeding is often unavoidable during liver transplantation (LT). However, blood transfusions are associated with risks and should be avoided whenever possible. This study compares preoperative factors and outcomes between non-transfusion and transfusion groups to identify variables that could be used to predict bloodless surgery in living donor liver transplantation (LDLT) patients.We conducted a retrospective study of 87 LDLT patients. The group of patients who did not require packed red blood cell (PRBC) transfusion (non-PRBC group, n = 44) was compared with those who did (PRBC group, n = 43). We compared risk factors, fluid management, and outcomes between the groups and identified variables for prediction of transfusion during LDLT.Compared with the PRBC group, the non-PRBC group had a lower model for end-stage liver disease (MELD) score (8.1 ±â€Š1.1 vs 18.2 ±â€Š8.8), international normalized ratio (INR) (1.16 ±â€Š0.1 vs 1.80 ±â€Š0.94), and partial thromboplastin time (PTT) (37.1 ±â€Š6.3 vs 54.1 ±â€Š24.0), but higher hemoglobin (Hb) (13.6 ±â€Š1.6 vs 11.5 ±â€Š2.2) and hematocrit (HCT) (39.1 ±â€Š4.4 vs 32.6 ±â€Š6.0). The non-PRBC group were more likely to receive colloid and albumin but had shorter intensive care unit (ICU) and hospital length of stay. The area under the receiver operative characteristic (ROC) curve of the MELD score was the highest (91%) using a cutoff value of 10.5.Patients without PRBC transfusion during LDLT were in better condition preoperatively and had better outcomes. The MELD score is a significant predictor for PRBC transfusion.

Inhaled nitric oxide therapy was not associated with postoperative acute kidney injury in patients undergoing lung transplantation: A retrospective pilot study.

Inhaled nitric oxide (iNO) therapy is commonly used in lung transplantation (LT) recipients during the perioperative periods. However, previous studies report that the use of iNO may increase the risk of renal dysfunction. Post-LT acute kidney injury (AKI) can lead to critical situations, including prolonged intensive care unit or hospital stays and increased morbidity and mortality. Accordingly, the aim of this study was to investigate the relationship between iNO therapy and incidence of post-LT AKI in LT recipients.The medical data of 36 patients who underwent LT surgery from January 2012 to July 2017 in a single university hospital setting were retrospectively collected and analyzed. Patients were divided into 2 groups: iNO (n = 14) and control (n = 19). The demographic data, anesthetic methods, complications, and perioperative laboratory test values of each patient were assessed. Patients were categorized according to changes in plasma creatinine (Cr) concentration levels within 48 hours after LT using Acute Kidney Injury Network criteria.There was no significant difference in the occurrence (P = .13) and severity (P = .9) of post-LT AKI between iNO and control groups. The mean serum Cr levels after surgery were 0.91 ±â€Š0.44 and 0.81 ±â€Š0.37 mg/dL in the iNO and control groups, respectively (P = .50).AKI plays a critical role in the prognosis of LT recipients. Our results revealed that iNO therapy was not associated with the incidence of post-LT AKI. Therefore, if iNO treatment is indicated, active use under close monitoring of renal function is recommended in LT-patients concerned about AKI after surgery.

Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide-Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression.

OBJECTIVE: To elucidate how ethanol extract of L. serratum (ELS) could exert anti-migratory effects on glioma with the suppression of nuclear factor kappa B (NF-κB) downstream pathway. METHODS: Cell viability of ELS on C6 glioma was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) assay and 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay were applied to measure NO production and reactive oxygen species (ROS) generation on lipopolysaccharide (LPS)-induced C6 glioma cells. NF-κB, mitogen-activated protein kinase (MAPK), inducible nictric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein were determined by Western blot. Wound healing assay was used to investigate the inhibitory effect of ELS on fetal bovine serum (FBS)-induced migration and matrix metalloproteinase (MMP)-9 and -2 activity was examined by zymography. RESULTS: ELS suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 through inhibiting the expression of chemokine CCL2 (or monocyte chemoattractant protein-1, MCP-1). In addition, ELS inhibited the expression of iNOS, COX-2, and the production of NO by LPS in C6 glioma cells. ELS also significantly decreased serum-induced migration of C6 glioma cells in scratch wound healing in a dose-dependent manner (P<0.01). The activity of MMP-9 and -2 were also significantly attenuated by ELS with LPS treatment (P<0.01). CONCLUSIONS: Our results suggest that downregulation of MMP-9 gene expression might be involved in the anti-migration effect of ELS against LPS-induced C6 glioma cells.

miR-150 enhances apoptotic and anti-tumor effects of paclitaxel in paclitaxel-resistant ovarian cancer cells by targeting Notch3.

Tumor recurrence by obtaining chemoresistance is a major obstacle to treating ovarian cancer. By TargetScan database and a luciferase reporter assay, we identified miR-150 directly targets Notch3, which is a key oncogene in ovarian cancer. We, therefore, investigated the role of miR-150 in ovarian cancer cells, and the usefulness of miR-150 as a therapeutic target in chemoresistant ovarian cancer, through examining miR-150 expression by qRT-PCR in ovarian cancer cell lines and tissues, and assessing the gain-of-function effect by WST, colony forming, TUNEL, wound healing and angiogenesis assays. Western blotting was performed to evaluate its downstream targets. The miR-150 expression was significantly downregulated in ovarian cancers. Treatment with pre-miR-150 significantly inhibited cancer cell proliferation, and induced apoptosis in PTX (paclitaxel) -resistant SKpac cells, which was not seen by PTX only treatment. On spheroid forming assay, an additional pre-miR-150 treatment with PTX decreased cancer stem cell activation in PTX-resistant SKpac cells. An experimental upregulation of miR-150 also decreased cancer cell migration and angiogenesis in SKpac cells. The Notch3 downstream proteins(NICD3 and HEY2), and cell cycle-related proteins (cyclinD3, pS6, and NF-kB), and apoptosis-related proteins (BCL-2 and BCL-W) were significantly downregulated by pre-miR-150 transfection. Taken together, miR-150 is related with PTX-resistance in ovarian cancer, and treatment with pre-miR-150 resensitizes cancer cells to PTX. Therefore, it may be a promising treatment strategy in chemoresistant and recurrent ovarian cancer.

The Association of Preoperative Body Mass Index with Acute Kidney Injury in Liver Transplantation Recipients: A Retrospective Study.

BACKGROUND: Liver transplantation (LT) is a complicated procedure with a high incidence of postoperative acute kidney injury (AKI). Previous studies indicate that even transient or mild post-LT AKI can result in critical conditions, including prolonged stays in hospitals and intensive care units and increased morbidity and mortality. The aim of this study was to investigate the association between body mass index (BMI) and occurrence of AKI in LT recipients. METHODS: Medical data from 203 patients who received LT surgery from January 2010 to August 2016 in a single university hospital setting were retrospectively collected and analyzed. Patients were classified as either underweight (BMI <20 kg/m2) or normal weight (20 ≤ BMI < 30 kg/m2). Demographic data, anesthetic methods, complications, and perioperative laboratory test values of each patient were assessed. Propensity analyses and logistic regression were performed to evaluate the association between BMI and post-LT AKI. RESULTS: There was no significant difference in occurrence of post-LT AKI between underweight and normal weight patients. The underweight patient group had significantly longer hospital stay compared with the normal weight patient group (P = 0.023). CONCLUSIONS: BMI classification was neither a positive nor negative predictor of postoperative AKI occurrence. However, patients with lower BMI had significantly longer hospital stay compared with their counterparts. Although our study was limited by its retrospective design, our observations suggest that lower BMI might play a role in post-LT AKI.

A Rice Gene Homologous to Arabidopsis AGD2-LIKE DEFENSE1 Participates in Disease Resistance Response against Infection with Magnaporthe oryzae.

ALD1 (ABERRANT GROWTH AND DEATH2 [AGD2]-LIKE DEFENSE1) is one of the key defense regulators in Arabidopsis thaliana and Nicotiana benthamiana. In these model plants, ALD1 is responsible for triggering basal defense response and systemic resistance against bacterial infection. As well ALD1 is involved in the production of pipecolic acid and an unidentified compound(s) for systemic resistance and priming syndrome, respectively. These previous studies proposed that ALD1 is a potential candidate for developing genetically modified (GM) plants that may be resistant to pathogen infection. Here we introduce a role of ALD1-LIKE gene of Oryza sativa, named as OsALD1, during plant immunity. OsALD1 mRNA was strongly transcribed in the infected leaves of rice plants by Magnaporthe oryzae, the rice blast fungus. OsALD1 proteins predominantly localized at the chloroplast in the plant cells. GM rice plants over-expressing OsALD1 were resistant to the fungal infection. The stable expression of OsALD1 also triggered strong mRNA expression of PATHOGENESIS-RELATED PROTEIN1 genes in the leaves of rice plants during infection. Taken together, we conclude that OsALD1 plays a role in disease resistance response of rice against the infection with rice blast fungus.