Ultrastructural Changes, Nuclear Factor-κB Activation, and Tumor Necrosis Factor-α Expression in Brain after Acute Normovolemic Hemodilution and Controlled Hypotension in Rats

Cilj Ispitati moždana oštećenja u štakora nakon različitih stupnjeva akutne normovolemične hemodilucije i kontrolirane hipotenzije s pomoću morfološke analize neurona i provjeriti aktivaciju jezgrenog faktora-κB (NF- κB) i izražaj čimbenika nekroze tumora-α (TNF-α). Postupci Četrdeset štakora nasumično je raspoređeno u one lažno operirane i one s normovolemičnom hemodilucijom i kontroliranom hipotenzijom (s hematokritom od 30%, 25%, 20%, and 15%). Normovolemična hemodilucija i kontrolirana hipotenzija izazvane su nakon što su osnovni fiziološki parametri praćeni 20 minuta. Kontrolirana hipotenzija izazvana je nakon 30 minuta s pomoću natrijeva nitroprusida, a srednji arterijski tlak održavao se sljedeći sat vremena na 50-60 mmHg. Tri i pol sata nakon operacije životinje su eutanazirane. Razina TNF-α i aktivnost NF-κB određene su u temporalnoj moždanoj kori. Ultrastrukturna oštećenja ocijenjena su u području CA1 u hipokampusu. Promjene mitohondrija ocijenjene su polukvantitativno. Rezultati U skupinama s hematokritom od 20% i 15% nađena su izražena ultrastrukturna oštećenja, poput denaturacije mitohondrija i izobličenja jezgara. Izražaj TNF-α i aktivnost NF-κB bila je značajno povišena u svim skupinama s normovolemičnom hemodilucijom i kontroliranom hipotenzijom, a najviše su bile u skupini s hematokritom od 25%. Zaključak Izražena normovolemična hemodilucija i kontrolirana hipotenzija s hematokritom ≤20% mogu izazvati moždana oštećenja pa ih treba izbjegavati. U stanju ishemije, aktivacija NF-κB i izražaj TNF-α mogu predstavljati funkcionalne korelate. Bolje upoznavanje uloge NF-κB i TNF-α u mozgu može otvoriti nove pristupe prevenciji i liječenju neuroloških bolesti.Aim To examine brain damage following different degrees of acute normovolemic hemodilution combined with controlled hypotension (ANH-CH) by neuronal morphological analysis and investigate the expression of nuclear factor-kappa B (NF-κB) activity and tumor necrosis factor-alpha (TNF-α) in the rat. Methods Forty rats were randomly assigned to receive a sham operation or ANH-CH (with hematocrit 30%, 25%, 20%, and 15%). ANH was performed after baseline physiological parameters had been monitored for 20 minutes. CH was induced 30 minutes later using sodium nitroprusside and mean arterial pressure was maintained at 50-60 mm Hg for 1 hour. Rats were euthanatized 3 and a half hours after operation. TNF-α levels and NF-κB activities in cerebral temporal cortex were measured. Ultrastructural alterations in the CA1 region of the rat hippocampi were observed. Changes in mitochondria were evaluated semiquantitatively. Results Marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the CA1 region of the hippocampus in the ANH-CH hematocrit 20% group and ANH-CH hematocrit 15% group. TNF-α expression and NF-κB activity in the cerebral temporal cortex significantly increased in all ANHCH groups and peaked in the ANH-CH hematocrit 25% group. Conclusion Severe ANH-CH with hematocrit ≤20% may induce cerebral damage and should be avoided. NF-κB activation and TNF-α expression may play a functional role under the ischemic condition. A better understanding of the role of NF-κB and TNF-α in the brain may lead to a novel approach for preventing and treating various neurological disorders

Optimization of a tri-drug treatment against lung cancer using orthogonal design in preclinical studies

A growing body of evidence suggests that anesthetics impact the outcome of patients with cancer after surgical intervention. However, the optimal dose and underlying mechanisms of co-administered anesthetics in lung tumor therapy have been poorly studied. Here, we aimed to investigate the role of combined anesthetics propofol, sufentanil, and rocuronium in treating lung cancer using an orthogonal experimental design and to explore the optimal combination of anesthetics. First, we evaluated the effects of the three anesthetics on the proliferation and invasion of A-549 cells using Cell Counting Kit 8 and Transwell migration and invasion assays. Subsequently, we applied the orthogonal experimental design (OED) method to screen the appropriate concentrations of the combined anesthetics with the most effective antitumor activity. We found that all three agents inhibited the proliferation of A-549 cells in a dose- and time-dependent manner when applied individually or in combination, with the highest differences in the magnitude of inhibition occurring 24 h after combined drug exposure. The optimal combination of the three anesthetics that achieved the strongest reduction in cell viability was 1.4 µmol/L propofol, 2 nmol/L sufentanil, and 7.83 µmol/L rocuronium. This optimal 3-drug combination produced a more beneficial result at 24 h than either single drug. Our results provide a theoretical basis for improving the efficacy of lung tumor treatment and optimizing anesthetic strategies

Risk factors for acute postoperative hypertension in non-cardiac major surgery: a case control study

Abstract Purpose Acute postoperative hypertension (APH) is a common complication during the anesthesia recovery period that can lead to adverse outcomes, including cardiovascular and cerebrovascular accidents. Identification of risk factors for APH will allow for preoperative optimization and appropriate perioperative management. This study aimed to identify risk factors for APH. Patients and methods In this retrospective single-center study, 1,178 cases were included. Data was entered by two investigators, and consistency analysis was performed by another. Patients were divided into APH and non-APH groups. A predictive model was built by multivariate stepwise logistic regression. The predictive ability of the logistic regression model was tested by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Hosmer and Lemeshow goodness-of-fit (GOF) test was performed to reflect the goodness of fit of the model. Calibration curve was created to represent the relationship between predicted risk and observed frequency. Sensitivity analysis was performed to evaluate the robustness of the results. Results Multivariate logistic regression analysis showed that age over 65 years (OR = 3.07, 95% CI: 2.14 ~ 4.42, P < 0.001), female patients (OR = 1.37, 95% CI: 1.02 ~ 1.84, P = 0.034), presence of intraoperative hypertension (OR = 2.15, 95% CI: 1.57 ~ 2.95, P < 0.001), and use of propofol in PACU (OR = 2.14, 95% CI: 1.49 ~ 3.06, P < 0.001) were risk factors for APH. Intraoperative use of dexmedetomidine (OR = 0.66, 95% CI: 0.49 ~ 0.89, P = 0.007) was a protective factor. Higher baseline SBP (OR = 0.90, 95% CI: 0.89 ~ 0.92, P < 0.001) also showed some correlation with APH. Conclusions The risk of acute postoperative hypertension increased with age over 65 years, female patients, intraoperative hypertension and restlessness during anesthesia recovery. Intraoperative use of dexmedetomidine was a protective factor for APH

Rapid fabrication of complex nanostructures using room-temperature ultrasonic nanoimprinting

Despite its advantages of scalable process and cost-effectiveness, nanoimprinting faces challenges with imprinting hard materials (e.g., crystalline metals) at low/room temperatures, and with fabricating complex nanostructures rapidly (e.g., heterojunctions of metal and oxide). Herein, we report a room temperature ultrasonic nanoimprinting technique (named nanojackhammer) to address these challenges. Nanojackhammer capitalizes on the concentration of ultrasonic energy flow at nanoscale to shape bulk materials into nanostructures. Working at room temperature, nanojackhammer allows rapid fabrication of complex multi-compositional nanostructures made of virtually all solid materials regardless of their ductility, hardness, reactivity and melting points. Atomistic simulations reveal a unique alternating dislocation generation and recovery mechanism that significantly reduces the imprinting force under ultrasonic cyclic loading. As a proof-of-concept, a metal-oxide-metal plasmonic nanostructure with built-in nanogap is rapidly fabricated and employed for biosensing. As a fast, scalable, and cost-effective nanotechnology, nanojackhammer will enable various unique applications of complex nanostructures in optoelectronics, biosensing, catalysis and beyond.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityPublished versionThis work was supported by Nanyang Technological University under NAP award (M408050000), and Singapore Ministry of Education Tier 1 program (2018-T1-001-051). The authors acknowledge the Facility for Analysis, Characterization, Testing and Simulation (FACTS), Nanyang Technological University Singapore for use of electron microscopy and X-ray facilities. B.D. and H.G. are grateful for a research start-up grant (002479-00001) from Nanyang Technological University and the Agency for Science, Technology and Research (A*STAR) and the use of the A*STAR Computational Resource Centre, Singapore (ACRC) and National Supercomputing Centre, Singapore (NSCC)