PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.
Chemoradiotherapy ; Colorectal Neoplasms ; Dysbiosis ; Fusobacterium ; Gastrointestinal Microbiome ; Genes, vif ; Genome ; Humans ; Microbiota ; Neoadjuvant Therapy ; Prevotella ; Radiotherapy ; Rectal Neoplasms ; Sequence Analysis, RNA ; Transcriptome

PURPOSE: Stress is associated with depression, which induces many psychiatric disorders. Serotonin, also known as 5-hydroxy-tryptamine (5-HT), acts as a biochemical messenger and regulator in the brain. It also mediates several important physiological functions. Depression is closely associated with an overactive bladder. In the present study, we investigated the effect of treadmill exercise on stress-induced depression while focusing on the expression of 5-HT 1A (5-H(1A)) receptors in the dorsal raphe. METHODS: Stress was induced by applying a 0.2-mA electric foot shock to rats. Each set of electric foot shocks comprised a 6-second shock duration that was repeated 10 times with a 30-second interval. Three sets of electric foot shocks were applied each day for 7 days. For the confirmation of depressive state, a forced swimming test was performed. To visualize the expression of 5-HT and tryptophan hydroxylase (TPH), immunohistochemistry for 5-HT and TPH in the dorsal raphe was performed. Expression of 5-H(1A) receptors was determined by western blot analysis. RESULTS: A depressive state was induced by stress, and treadmill exercise alleviated the depression symptoms in the stress-induced rats. Expressions of 5-HT, TPH, and HT 1A in the dorsal raphe were reduced by the induction of stress. Treadmill exercise increased 5-HT, TPH, and HT 1A expressions in the stress-induced rats. CONCLUSIONS: Treadmill exercise enhanced 5-HT synthesis through the up-regulation of 5-HT(1A) receptors, and improved the stress-induced depression. In the present study, treadmill exercise improved depression symptoms by enhancing 5-HT(1A) receptor expression. The present results suggest that treadmill exercise might be helpful for the alleviation of overactive bladder and improve sexual function.
Animals ; Blotting, Western ; Brain ; Depression* ; Exercise Test ; Exercise* ; Foot ; Immunohistochemistry ; Physical Exertion ; Rats* ; Receptor, Serotonin, 5-HT1A* ; Serotonin ; Shock ; Stress, Psychological ; Tryptophan Hydroxylase ; Up-Regulation* ; Urinary Bladder, Overactive

No abstract available.
Glycopeptides*

BACKGROUND: Recent studies demonstrated that volatile anesthetics suppress the NO-cGMP system in the vascular system. It has been known that the hemodynamic changes produced by volatile anesthetics in septic patients are mediated by upregulation of iNOS leading to excessive release of NO. The mechanisms underlying suppression of the NO-cGMP system by anesthetics are still controversial. It has been elucidated that nitric oxide synthase (NOS) plays a major role in the regulatory function in the L-arginine-NO system. So we examined the effects of NOS inhibitor (L-NAME, aminoguanidine) and NO scavenger (hydroxocobalamin) on vascular smooth muscle contractile function in lipopolysaccharide (LPS)-treated rat aorta during halothane administration. METHODS: Aortic ring preparations were obtained from LPS-treated (1.5 mg/kg, ip, for 18 h) rats. We evaluated the effects of hydroxocobalamin, L-NAME and aminoguanidine on contractile responses to phenylephrine during halothane (1 & 2 MAC) administration respectively. Statistical significances (P<0.05) were analyzed according to data characterictics by repeated measures ANOVA test and student's t-test. RESULTS: The contractile responses to phenylephrine in LPS-treated rats aorta were significantly (P<0.05) increased in the presence of hydroxocobalamin and L-NAME. During the halothane (1 and 2 MAC) administration, the contractile responses to phenylephrine in LPS-treated rats aorta were increased significantly (P<0.05) in the presence of hydroxocobalamin and L-NAME. CONCLUSIONS: From these results, it is suggested that hydroxocobalamin and L-NAME may be useful in the therapy of septic shock.
Anesthetics ; Animals ; Aorta ; Halothane* ; Hemodynamics ; Humans ; Hydroxocobalamin* ; Muscle, Smooth, Vascular ; NG-Nitroarginine Methyl Ester* ; Nitric Oxide Synthase ; Phenylephrine ; Rats* ; Shock, Septic ; Up-Regulation

BACKGROUND: Anesthesia and surgery may exacerbate liver function in patients with pre-existing liver disease so it is important to choose less hepatotoxic anesthetics in patients with chronic liver disease. METHODS: This study was designed to examine the postoperative liver function test in 150 patients after hepatectomy with portal triad clamping through retrospective chart review. Patients were divided into an isoflurane group (group I, n = 56) and a propofol group (group P, n = 57) by used anesthetics for maintaining anesthesia. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, alkaline phosphatase, total bilirubin, albumin, and prothrombin time were checked at preoperation, and postoperatively at 1, 3, 7 and 14 days in the two groups. Indocyanine retention rate (ICG-R15) was measured at preoperation, and postoperatively at 1 and 7 days. RESULTS: AST values increased postoperatively at 1, 3, 7, and 14 days compared with preoperation. ALT values increased postoperatively at 1, 3 and 7 days compared with preoperation and there was difference between group I (443.8 +/- 52.1 U/L) and group P (202.7 +/- 24.7 U/L) at postoperative 1 day. Other values had no significant difference between the two groups. CONCLUSIONS: Though it might need a well controlled study to find the differences in effect between isoflurane and propofol on the postoperative liver function test, we concluded that total intravenous anesthesia using propofol is also one of the safest anesthetic methods for hepatic resection with minimal hepatotoxicity.
Alanine Transaminase ; Alkaline Phosphatase ; Anesthesia ; Anesthesia, Intravenous ; Anesthetics ; Aspartate Aminotransferases ; Bilirubin ; Constriction* ; Hepatectomy ; Humans ; Isoflurane* ; L-Lactate Dehydrogenase ; Liver Diseases ; Liver Function Tests* ; Liver* ; Propofol* ; Prothrombin Time ; Retrospective Studies

Purpose: Surgical resection, the primary treatment for colorectal cancer (CRC), is often linked with postoperative complications that adversely affect the overall survival rates (OS). The pan-immune-inflammation value (PIV), a novel biomarker, is promising in evaluating cancer prognoses. We aimed to explore the impact of preoperative immune inflammation status on postoperative and long-term oncological outcomes in patients with CRC. Methods: A retrospective analysis of 203 patients with CRC who underwent surgery (January 2016–June 2020) was conducted. The preoperative PIV was calculated as [(neutrophil count + platelet count + monocyte count) / lymphocyte counts]. The PIV optimal cutoff value was determined based on the OS using the Contal and O’Quigley methods. Results: A PIV value ≥155.90 was defined as high. Patients were categorized into low-PIV (n = 85) and high-PIV (n = 118) groups. Perioperative clinical outcomes (total operation time, time to gas out, sips of water, soft diet, and hospital stay) were not significantly different between the groups. The high-PIV group exhibited more postoperative complications (P = 0.024), and larger tumor size compared with the low-PIV group. Multivariate analysis identified that American Society of Anesthesiologists grade III (P = 0.046) and high-PIV (P = 0.049) were significantly associated with postoperative complications. The low-PIV group demonstrated higher OS (P = 0.001) and disease-free survival rates (DFS) (P = 0.021) compared with the high-PIV group. Advanced N stage (P = 0.005) and high-PIV levels (P = 0.047) were the identified independent prognostic factors for OS, whereas advanced N stage (P = 0.045) was an independent prognostic factor for DFS. Conclusion Elevated preoperative PIV was associated with an increased incidence of postoperative complications and served as an independent prognostic factor for OS.

PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.
Animals ; Apoptosis ; Astrocytes ; Blotting, Western ; Calbindins ; Cell Count ; Cerebellar Vermis ; Cerebellum ; Gait ; Glial Fibrillary Acidic Protein ; Immunohistochemistry ; Microglia ; Models, Animal ; Neurodegenerative Diseases ; Parkinson Disease* ; Parturition ; Posture ; Purkinje Cells* ; Rats* ; Rotenone ; Running ; Tremor

The objective of this study was to analyze the concurrent treatment effects of ursolic acid (UA) and low-intensity treadmill exercise and to confirm the effectiveness of UA as an exercise mimetic to safely improve muscle atrophy-related diseases using Sprague-Dawley (SD) rats with skeletal muscle atrophy. Significant muscle atrophy was induced in male SD rats through hind limb immobilization using casting for 10 days. The muscle atrophy-induced SD rats were group into four: SED, sedentary; UA, daily intraperitoneal UA injection, 5 mg/kg; EX, low-intensity (10–12 m/min, 0° grade) treadmill exercise; and UEX, daily intraperitoneal UA injection, 5 mg/kg, and low-intensity (10–12 m/min, 0° grade) treadmill exercise. After 8 weeks of treatment, endurance capacity was analyzed using a treadmill, and tissues were extracted for analysis of visceral fat mass, body weight, muscle mass, expression of muscle atrophy- and hypertrophy-related genes, and endurance capacity. Although the effects of body weight gain control, muscle mass increase, and endurance capacity improvement were inadequate in the UA group, significant results were confirmed in the UEX group. The UEX group had significantly reduced body weight and visceral fat, significantly improved mass of tibialis anterior and gastrocnemius muscles, and significantly decreased atrophy-related gene expression of MuRF1 and atrogin-1, but did not have significant change in hypertrophy-related gene expression of Akt and mTOR. The endurance capacity was significantly improved in the EX and UEX groups. These data suggest that concurrent treatment with low-intensity exercise and UA is effective for atrophy-related physical dysfunctions.
Aging ; Animals ; Atrophy ; Body Weight ; Extremities ; Gene Expression ; Humans ; Immobilization ; Intra-Abdominal Fat ; Male ; Muscle, Skeletal ; Muscles ; Muscular Atrophy* ; Rats* ; Rats, Sprague-Dawley

Sodium nitroprusside (SNP) is an anti-hypertensive drug, commonly used to decrease the systemic vascular resistance and lower the blood pressure. When the amount of cyanide generated by the SNP exceeds the metabolic capacity for detoxification, cyanide toxicity occurs. Under general anesthesia and cardiopulmonary bypass (CPB), it may be difficult to detect the development of cyanide toxicity. In cardiac surgical patients, hemolysis, hypothermia and decreased organ perfusion, which emphasize the risk of cyanide toxicity, may develop as a consequence of CPB. In particular, hemolysis during CPB may cause an unexpected overproduction of cyanide due to free hemoglobin release. We experienced a patient who demonstrated SNP tachyphylaxis and cyanide toxicity during CPB, even though the total amount of SNP administered was much lower than the recommended dose. We therefore report this case with a review of the relevant literature.
Anesthesia, General ; Blood Pressure ; Cardiopulmonary Bypass* ; Cyanides ; Hemolysis ; Humans ; Hypothermia ; Nitroprusside* ; Perfusion ; Tachyphylaxis ; Vascular Resistance

BACKGROUND: The purpose of this study was to investigate the effectiveness of ondansetron and midazolam in the prevention of PONV after thyroidectomy. METHODS: One hundred nineteen women undergoing thyroidectomy under general anesthesia were randomized to receive midazolam 0.075 mg/kg (Group M, n = 41), ondansetron 4 mg (Group O, n = 39), or normal saline 10 ml (Group C, n = 39) intravenously. The incidence and severity of nausea, vomiting, and pain were assessed as 6 and 24 h after the end of surgery. RESULTS: The incidence of PONV was 34% in Group M, 46% in Group O, and 64% in Group C, which showed a significant difference between Group C and Group M, but not Group O. However, there were no significant differences between groups in pain scores and the incidence of sedation. CONCLUSIONS: We recommend the use of midazolam as an effective antiemetic after thyroidectomy.
Anesthesia, General ; Female ; Humans ; Incidence ; Midazolam* ; Nausea ; Ondansetron* ; Postoperative Nausea and Vomiting* ; Thyroidectomy* ; Vomiting