BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases

Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings

Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Design of Closed-Loop Control Schemes Based on the GA-PID and GA-RBF-PID Algorithms for Brain Dynamic Modulation

Neurostimulation can be used to modulate brain dynamics of patients with neuropsychiatric disorders to make abnormal neural oscillations restore to normal. The control schemes proposed on the bases of neural computational models can predict the mechanism of neural oscillations induced by neurostimulation, and then make clinical decisions that are suitable for the patient’s condition to ensure better treatment outcomes. The present work proposes two closed-loop control schemes based on the improved incremental proportional integral derivative (PID) algorithms to modulate brain dynamics simulated by Wendling-type coupled neural mass models. The introduction of the genetic algorithm (GA) in traditional incremental PID algorithm aims to overcome the disadvantage that the selection of control parameters depends on the designer’s experience, so as to ensure control accuracy. The introduction of the radial basis function (RBF) neural network aims to improve the dynamic performance and stability of the control scheme by adaptively adjusting control parameters. The simulation results show the high accuracy of the closed-loop control schemes based on GA-PID and GA-RBF-PID algorithms for modulation of brain dynamics, and also confirm the superiority of the scheme based on the GA-RBF-PID algorithm in terms of the dynamic performance and stability. This research of making hypotheses and predictions according to model data is expected to improve and perfect the equipment of early intervention and rehabilitation treatment for neuropsychiatric disorders in the biomedical engineering field

Synergistic Acid-Catalyzed Synthesis of <i>N</i>‑Aryl-Substituted Azacycles from Anilines and Cyclic Ethers

A metal-free and efficient approach to <i>N</i>-aryl-substituted azacycles from arylamines and cyclic ethers is described. In this synthesis, the synergistic effect between Lewis and Brønsted acids is crucial to the ring-opening of cyclic ethers and the subsequent cyclization. The use of B­(C₆F₅)₃ enabled the formation of frustrated Lewis pairs (FLPs) from the reactants, and the resulting FLPs allowed ready access to the <i>N</i>-arylazacycles in moderate to good yields via further cyclization. Water is the sole waste resulting from the reaction, thereby making it an environmentally benign process

Efficient Benzylic and Aliphatic C–H Oxidation with Selectivity for Methylenic Sites Catalyzed by a Bioinspired Manganese Complex

A benzimidazole-based nonheme manganese complex efficiently catalyzes benzylic, aliphatic C–H as well as tertiary C–H oxidation with hydrogen peroxide as the oxidant in the presence of acetic acid as additive. ¹⁸O labeling experiments suggest the reaction may proceed via a high-valent manganese-oxo intermediate

Highly Efficient Oxidation of Secondary Alcohols to Ketones Catalyzed by Manganese Complexes of N₄ Ligands with H₂O₂

The manganese complex Mn­(<i>S</i>-PMB)­(CF₃SO₃)₂ was proven to be highly efficient in the catalytic oxidation of several benzylic and aliphatic secondary alcohols with H₂O₂ as the oxidant and acetic acid as the additive. A maximum turnover number of 4700 was achieved in the alcohol oxidation. In addition, the Hammett analysis unveiled the electrophilic nature of this manganese catalyst with N₄ ligand