Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.

A mammalian cell houses two genomes located separately in the nucleus and mitochondria. During evolution, communications and adaptations between these two genomes occur extensively to achieve and sustain homeostasis for cellular functions and regeneration. Mitochondria provide the major cellular energy and contribute to gene regulation in the nucleus, whereas more than 98% of mitochondrial proteins are encoded by the nuclear genome. Such two-way signaling traffic presents an orchestrated dynamic between energy metabolism and consumption in cells. Recent reports have elucidated the way how mitochondrial bioenergetics synchronizes with the energy consumption for cell cycle progression mediated by cyclin B1/CDK1 as the communicator. This review is to recapitulate cyclin B1/CDK1 mediated mitochondrial activities in cell cycle progression and stress response as well as its potential link to reprogram energy metabolism in tumor adaptive resistance. Cyclin B1/CDK1-mediated mitochondrial bioenergetics is applied as an example to show how mitochondria could timely sense the cellular fuel demand and then coordinate ATP output. Such nucleus-mitochondria oscillation may play key roles in the flexible bioenergetics required for tumor cell survival and compromising the efficacy of anti-cancer therapy. Further deciphering the cyclin B1/CDK1-controlled mitochondrial metabolism may invent effect targets to treat resistant cancers

Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures

OBJECTIVE: The ideal solution for fluid management during neurosurgical procedures remains controversial. The aim of this study was to compare the effects of a 7.2% hypertonic saline - 6% hydroxyethyl starch (HS-HES) solution and a 6% hydroxyethyl starch (HES) solution on clinical, hemodynamic and laboratory variables during elective neurosurgical procedures. METHODS: Forty patients scheduled for elective neurosurgical procedures were randomly assigned to the HS-HES group orthe HES group. Afterthe induction of anesthesia, patients in the HS-HES group received 250 mL of HS-HES (500 mL/h), whereas the patients in the HES group received 1,000 mL of HES (1000 mL/h). The monitored variables included clinical, hemodynamic and laboratory parameters. Chictr.org: ChiCTR-TRC-12002357 RESULTS: The patients who received the HS-HES solution had a significant decrease in the intraoperative total fluid input (

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023

Simulation Data.zip

This package includes our designed model and simulation data in two kinds of networks with 1005 and 2540 nodes, respectively. The model is built based on Anylogic software. </p

Facile engineering of chitosan-coated aminopterin loaded zeolitic imidazolate framework: promising drug delivery system for breast cancer

AbstractIn this study, we have designed an anticancer drug delivery framework by a one-pot technique using a zeolitic imidazolate framework (ZIF) as the carrier. The chitosan-coated Aminopterin (AMT) loaded with zeolitic imidazolate framework (ZIF-90) CS@AMT@ZIF-90 (CAZ-90) for breast cancer cells. The particle’s outer layer changed Chitosan (CS), a pH-sensitive biomaterial, to increase the composite CAZ-90’s reactivity to pH during drug release. CAZ-90 displayed target-selective and pH-responsive by releasing a significant ratio of AMT under an acidic milieu and a considerably reduced amount of AMT in a normal milieu. Additionally, CAZ-90 was found to have low toxicity to normal Human umbilical vein endothelial cells (HUVECs) cells while inhibiting breast cancer 4T1, MDA-MB-231, and MCF-7 cells in vitro. Further, cell death was investigated by two different staining methods (AO-EB and DAPI nuclear staining). RNase-PI staining by flow cytometry techniques investigated the cell cycle arrest in breast (4T1, MDA-MB-231, and MCF-7) cancer cells. CAZ-90 showed high AMT drug loading, cancer-targeted release, and excellent biocompatibility in the related tests, making it a promising option for an anticancer drug delivery system

Response Analysis of Asymmetric Monostable Harvesters Driven by Color Noise and Band-Limited Noise

In this paper, we investigate the response of asymmetric potential monostable energy harvesters (MEHs) excited by color noise and band-limited noise. The motivation for this study is that environmental vibrations always have the characteristic of randomness, and it is difficult to modulate a perfectly symmetric MEH. For the excitation of exponentially correlated color noise, the moment differential equation was applied to evaluate the output performance of the asymmetric potential MEHs. Numerical and theoretical analyses were carried out to investigate the influence of noise intensity and internal system parameters on the output power of the system. Our results demonstrate that the output performance of the asymmetric MEH decreases with the increase in the correlation time, which determines the character of the color noise. On the contrary, the increase in the asymmetric degree enhances the output power of the asymmetric MEH subjected to color noise. For the band-limited noise excitation, numerical simulation is undertaken to consider the response of the asymmetric MEHs, and outcomes indicate that the frequency bandwidth and center frequency have a significant influence on the output performance. Regarding the asymmetric potential, its appearance leads the MEHs to generate higher output power at lower frequencies and this phenomenon is more obvious with the increase in the degree of asymmetry. Finally, we observed that the characteristics of the response bandwidth of asymmetric MEHs subjected to band-limited noise excitation are similar to the response under harmonic excitation