Cardiopulmonary Response to Robot-Assisted Tilt Table With Regard to Its Components.

Cardiopulmonary function is exceptionally critical during the early stages of rehabilitation after neurological disorders such as stroke, spinal cord injury and Parkinson's disease. This study aimed to demonstrate how robot-assisted and tilt table exercises affect cardiopulmonary function. In this study, ten healthy young adults performed six combinations of conditions according to robot-assisted mode (on/off), angle of tilt table (20°/60°), and functional electrical stimulation (FES) mode (on/off). Four conditions had FES mode off with combinations of robot-assisted mode (on/off) and tilt angle (20°/60°) and two conditions had robot-assisted mode and FES on with tilt angle (20°/60°). Cardiopulmonary effects (oxygen uptake [VO2], peak oxygen uptake [VO2peak], metabolic energy cost [MET], rate pressure product [RPP], heart rate [HR], maximum heart rate [%HRmax], and minute ventilation [VE]) were compared in each condition. As a result, in the angle and FES mode effect, VO2, VO2peak, MET, RPP, HR, and %HRmax, unlike that for VE, showed major effects in angle. In addition, in the robot-assisted mode and angle effect, when the FES was switched off, VO2, METs, and VE values showed major effects in the robot-assisted mode, whereas all other values showed major effects in angle. Compared to earlier reported findings, we can expect that robot-assisted tilt table training can lead to changes in the cardiopulmonary function.

Chloroquine reverses chemoresistance via upregulation of p21WAF1/CIP1 and autophagy inhibition in ovarian cancer.

Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells. The CQ-CDDP combination significantly decreased cell proliferation and increased apoptosis in all cell lines. The combination induced expression of γH2AX, a DNA damage marker protein, and induced G2/M cell cycle arrest. Although the CQ-CDDP combination decreased protein expression of ATM and ATR, phosphorylation of ATM was increased and expression of p21WAF1/CIP1 was also increased in CQ-CDDP-treated cells. Knockdown of p21WAF1/CIP1 by shRNA reduced the expression of γH2AX and phosphorylated ATM and inhibited caspase-3 activity but induced ATM protein expression. Knockdown of p21WAF1/CIP1 partly inhibited CQ-CDDP-induced G2/M arrest, demonstrating that knockdown of p21WAF1/CIP1 overcame the cytotoxic effect of the CQ-CDDP combination. Ectopic expression of p21WAF1/CIP1 in CDDP-treated ATG5-shRNA/A2780-CP20 cells increased expression of γH2AX and caspase-3 activity, demonstrating increased DNA damage and cell death. The inhibition of autophagy by ATG5-shRNA demonstrated similar results upon CDDP treatment, except p21WAF1/CIP1 expression. In an in vivo efficacy study, the CQ-CDDP combination significantly decreased tumor weight and increased expression of γH2AX and p21WAF1/CIP1 in A2780-CP20 orthotopic xenografts and a drug-resistant patient-derived xenograft model of EOC compared with controls. These results demonstrated that CQ increases cytotoxicity in combination with CDDP by inducing lethal DNA damage by induction of p21WAF1/CIP1 expression and autophagy inhibition in CDDP-resistant EOC.

Cucurbitacin D Induces G2/M Phase Arrest and Apoptosis via the ROS/p38 Pathway in Capan-1 Pancreatic Cancer Cell Line.

Pancreatic cancer has a poor prognosis with a five-year survival rate of less than 10%. Moreover, chemotherapy is mostly rendered ineffective owing to chemotherapy resistance and cytotoxicity. Therefore, the development of effective therapeutic strategies and novel drugs against pancreatic cancer is an urgent need. Cucurbitacin D (CuD), a plant steroid derived from Trichosanthes kirilowii, is an anticancer agent effective against various cancer cell lines. However, the anticancer activity and molecular mechanism of CuD in pancreatic cancer remain unknown. Therefore, we aimed to investigate the anticancer activity and molecular mechanism of CuD in the human pancreatic cancer cell line, Capan-1. CuD induced cell cycle arrest at the G2/M phase, apoptosis, and reactive oxygen species generation in Capan-1 cell line. In addition, CuD induced the activation of the p38 MAPK signaling pathway that regulates apoptosis, which was also inhibited by N-acetyl-L-cysteine and the p38 inhibitor SB203580. These data suggest that CuD induces cell cycle arrest and apoptosis via the ROS/p38 pathway in Capan-1 pancreatic cancer cell line; hence, CuD is a promising candidate that should be explored further for its effectiveness as an anticancer agent against pancreatic cancer.

Pattern identification of lung cancer patients based on body constitution questionnaires (BCQ) and glycoproteomics for precision medicine.

BACKGROUND: The patient's pattern identification has been used for personalized medicine in traditional Korean medicine (TKM) and aims for patient-specific therapy by Korean medical doctors. The pattern identification in this trial will be diagnosed from body constitution questionnaire (BCQ) with a more objective diagnosis of it but this method still needs a more concrete scientific basis. Glycoproteins are well-known to be associated with diseases (especially cancers) so glycoproteomics can be applied to differentiate pattern identification types of lung cancer patients. Thus, for the first time proteomics approach will be applied to the pattern identification by comparing BCQ assessment in order to establish a scientific basis with clinical proteomics for precision medicine. METHODS: This observational trial will at first diagnose the pattern identification types of lung cancer patients with BCQ assessment and then elucidate their relationships with proteomics. Blood samples will be collected before surgery along with clinical information of participants. The patients' pattern identification in TKM will be diagnosed from BCQ assessment. Then, lung cancer patients will be divided and pooled into 3 lung cancer entire (LCE) groups according to their pattern identification types (Xu, Stasis, or Gentleness). Three lung cancer representative (LCR) groups will be selected and pooled from each LCE group by selecting those with the same control factors. The 3 LCE groups and the 3 LCR groups from lung cancer patients will be independently analyzed through the glycoproteomics approach based on the patients' pattern identification. Glycoproteins from the 6 groups will be identified through proteomics approach and then categorized for analysis. DISCUSSION: This study intends to diagnose pattern identification of patients in TKM with BCQ assessment and proteomics approach. The identification of the glycoproteins in each group will lead to the scientific foundation of personalized medicine in TKM according to patients' pattern identification for lung cancer therapy. We intend to(1) diagnose the pattern identification types of lung cancer patients with BCQ under the framework of TKM;(2) evaluate BCQ assessment with glycoproteomics approach for precision medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT03384680. Registered 27 December 2017. Retrospectively registered.

Anti-microbial, anti-biofilm activities and cell selectivity of the NRC-16 peptide derived from witch flounder, Glyptocephalus cynoglossus.

Previous studies had identified novel antimicrobial peptides derived from witch flounder. In this work, we extended the search for the activity of peptide that showed antibacterial activity on clinically isolated bacterial cells and bacterial biofilm. Pseudomonas aeruginosa was obtained from otitis media and cholelithiasis patients, while Staphylococcus aureus was isolated from otitis media patients. We found that synthetic peptide NRC-16 displays antimicrobial activity and is not sensitive to salt during its bactericidal activity. Interestingly, this peptide also led to significant inhibition of biofilm formation at a concentration of 4-16 µM. NRC-16 peptide is able to block biofilm formation at concentrations just above its minimum inhibitory concentration while conventional antibiotics did not inhibit the biofilm formation except ciprofloxacin and piperacillin. It did not cause significant lysis of human RBC, and is not cytotoxic to HaCaT cells and RAW264.7 cells, thereby indicating its selective antimicrobial activity. In addition, the peptide's binding and permeation activities were assessed by tryptophan fluorescence, calcein leakage and circular dichroism using model mammalian membranes composed of phosphatidylcholine (PC), PC/cholesterol (CH) and PC/sphingomyelin (SM). These experiments confirmed that NRC-16 does not interact with any of the liposomes but the control peptide melittin did. Taken together, we found that NRC-16 has potent antimicrobial and antibiofilm activities with less cytotoxicity, and thus can be considered for treatment of microbial infection in the future.