Comparative observation of the effectiveness and safety of remimazolam besylate versus dexmedetomidine in gastrointestinal surgery in obese patients.

BACKGROUND: Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. AIM: To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. METHODS: The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). RESULTS: At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO2 than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. CONCLUSION: Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

Exploring adequate CO2 elevation for optimum tomato growth and yield under protected cultivation.

The adequate elevation of CO2 concentrations (e [CO2]) could not be assessed by constrained analysis of comparative experimental study for optimum plant growth and yield with improved fruit quality owing to the lack of conjunctive investigation of plant parametric responses. Instead, the principal component analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS) assessed and quantified the parametric plant responses to identify the adequate level of e [CO2] for optimum plant growth and yield. In this study, tomato plants were grown under an ambient CO2 (a [CO2], 500 µmol mol-1) and three e [CO2] (700, 850 and 1000 µmol mol-1): named EC700, EC850 and EC1000, respectively, in autumn-winter (AW) 2020 and spring summer (SS) 2021 growing seasons to investigate and evaluate the plant parametric responses under e [CO2]. The tomato plant's response with maximum transportability of biomass to fruits was observed under 700 µmol mol-1. The plant height, stem diameter and LAI were enhanced compared to a [CO2] at the optimum level under 1000 µmol mol-1 (by 50.53, 20.98 and 44.44%) and 700 µmol mol-1 (by 22.41, 12.09 and 26.88%) in Aw 2020; Ss 2021, respectively. The optimum yield was increased under 700 µmol mol-1 by 73.95% and 55.58% in Aw 2020; Ss 2021, respectively. EC700 was ranked as a priority by TOPSIS with 0.632 and 0.694 plant response performance index in Aw 2020; Ss 2021, respectively, to get optimum tomato growth, yield, water use efficiency and fruit quality. The results of this study are beneficial for commercial greenhouse crop production by fumigating the adequate level of e [CO2], to reduce the cost of CO2 fertigation, enhance the yield and save the water quantity.

Improvement of Biomineralization of Sporosarcina pasteurii as Biocementing Material for Concrete Repair by Atmospheric and Room Temperature Plasma Mutagenesis and Response Surface Methodology.

Microbially induced calcium carbonate precipitation (MICP) has recently become an intelligent and environmentally friendly method for repairing cracks in concrete. To improve on this ability of microbial materials concrete repair, we applied random mutagenesis and optimization of mineralization conditions to improve the quantity and crystal form of microbially precipitated calcium carbonate. Sporosarcina pasteurii ATCC 11859 was used as the starting strain to obtain the mutant with high urease activity by atmospheric and room temperature plasma (ARTP) mutagenesis. Next, we investigated the optimal biomineralization conditions and precipitation crystal form using Plackett-Burman experimental design and response surface methodology (RSM). Biomineralization with 0.73 mol/l calcium chloride, 45 g/l urea, reaction temperature of 45°C, and reaction time of 22 h, significantly increased the amount of precipitated calcium carbonate, which was deposited in the form of calcite crystals. Finally, the repair of concrete using the optimized biomineralization process was evaluated. A comparison of water absorption and adhesion of concrete specimens before and after repairs showed that concrete cracks and surface defects could be efficiently repaired. This study provides a new method to engineer biocementing material for concrete repair.

Regulation of mitochondrial cristae remodelling by acetylcholine alleviates palmitate-induced cardiomyocyte hypertrophy.

Mitochondrial dysfunction is associated with obesity-induced cardiac remodelling. Recent research suggests that the cristae are the true bioenergetic components of cells. Acetylcholine (ACh), the major neurotransmitter of the vagus nerve, exerts cardio-protective effects against ischaemia. This study investigated the role of cristae remodelling in palmitate (PA)-induced neonatal rat cardiomyocyte hypertrophy and explored the beneficial effects of ACh. We found loose, fragmented and even lysed cristae in PA-treated neonatal cardiomyocytes along with declines in mitochondrial network and complex expression and overproduction of mitochondrial reactive oxygen species (ROS); these changes ultimately resulted in increased myocardial size. Overexpression of mitofilin by adenoviral infection partly improved cristae shape, mitochondrial network, and ATP content and attenuated cell hypertrophy. Interestingly, siRNA-mediated AMP-activated protein kinase (AMPK) silencing increased the number of cristae with a balloon-like morphology without disturbing mitofilin expression. Furthermore, AMPK knockdown abolished the effects of mitofilin overexpression on cristae remodelling and inhibited the interaction of mitofilin with sorting and assembly machinery 50 (Sam50) and coiled-coil helix coiled-coil helix domain-containing protein 3 (CHCHD3), two core components of the mitochondrial contact site and cristae organizing system (MICOS) complex. Intriguingly, ACh upregulated mitofilin expression and AMPK phosphorylation via the muscarinic ACh receptor (MAChR). Moreover, ACh enhanced protein-protein interactions between mitofilin and other components of the MICOS complex, thereby preventing PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy; however, these effects were abolished by AMPK silencing. Taken together, our data suggest that ACh improves cristae remodelling to defend against PA-induced myocardial hypertrophy, presumably by increasing mitofilin expression and activating AMPK to form the MICOS complex through MAChR. These results suggest new and promising therapeutic approaches targeting mitochondria to prevent lipotoxic cardiomyopathy.

[Recent progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis].

Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a "healthy" state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.

Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.

AIMS: Obesity is associated with increased cardiovascular morbidity and mortality. It is accompanied by augmented O-linked ß-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux. However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear. MAIN METHODS: High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh). KEY FINDINGS: PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice. HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner. Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK). Interestingly, ACh significantly blocked damage to HUVECs induced by HG. Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor). Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh. SIGNIFICANCE: Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.

Pyridostigmine alleviates cardiac dysfunction via improving mitochondrial cristae shape in a mouse model of metabolic syndrome.

Insulin resistance and autonomic imbalance are important pathological processes in metabolic syndrome-induced cardiac remodeling. Recent studies determined that disruption of mitochondrial cristae shape is associated with myocardial ischemia; however, the change in cristae shape in metabolic syndrome-induced cardiac remodeling remains unclear. This study determined the effect of pyridostigmine (PYR), which reversibly inhibits cholinesterase to improve autonomic imbalance, on high-fat diet (HFD)-induced cardiac insulin resistance and explored the potential effect on the shape of mitochondrial cristae. Feeding of a HFD for 22 weeks led to an irregular and even lysed cristae structure in cardiac mitochondria, which contributed to decreased mitochondrial content and ATP production and increased oxygen species production, ultimately impairing insulin signaling and lipid metabolism. Interestingly, PYR enhanced vagal activity by increasing acetylcholine production and exerted mito-protective effects by activating the LKB1/AMPK/ACC signal pathway. Specifically, PYR upregulated OPA1 and Mfn1/2 expression, promoted the formation of the mitofilin/CHCHD3/Sam50 complex, and decreased p-Drp1 and Fis1 expression, resulting in tight and parallel cristae and increasing cardiac mitochondrial complex subunit expression and ATP generation as well as decreasing release of cytochrome C from mitochondria and oxidative damage. Furthermore, PYR improved glucose and insulin tolerance and insulin-stimulated Akt phosphorylation, decreased lipid toxicity, and ultimately ameliorated HFD-induced cardiac remodeling and dysfunction. In conclusion, PYR prevented cardiac and insulin insensitivity and remodeling by stimulating vagal activity to regulate mitochondrial cristae shape and function in HFD-induced metabolic syndrome in mice. These results provide novel insights for the development of a therapeutic strategy for obesity-induced cardiac dysfunction that targets mitochondrial cristae.

Choline ameliorates cardiac hypertrophy by regulating metabolic remodelling and UPRmt through SIRT3-AMPK pathway.

AIMS: Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline. METHODS AND RESULTS: The experiments were conducted using a model of ventricular hypertrophy by partially banding the abdominal aorta of Sprague Dawley rats. Cardiomyocyte size and cardiac fibrosis were significantly increased in hypertrophic hearts. In vitro cardiomyocyte hypertrophy was induced by exposing neonatal rat cardiomyocytes to angiotensin II (Ang II) (10-6 M, 24 h). Choline attenuated the mito-nuclear protein imbalance and activated the mitochondrial-unfolded protein response (UPRmt) in the heart, thereby preserving the ultrastructure and function of mitochondria in the context of cardiac hypertrophy. Moreover, choline inhibited myocardial metabolic dysfunction by promoting the expression of proteins involved in ketone body and fatty acid metabolism in response to pressure overload, accompanied by the activation of sirtuin 3/AMP-activated protein kinase (SIRT3-AMPK) signalling. In vitro analyses demonstrated that SIRT3 siRNA diminished choline-mediated activation of ketone body metabolism and UPRmt, as well as inhibition of hypertrophic signals. Intriguingly, serum from choline-treated abdominal aorta banding models (where ß-hydroxybutyrate was increased) attenuated Ang II-induced myocyte hypertrophy, which indicates that ß-hydroxybutyrate is important for the cardioprotective effects of choline. CONCLUSION: Choline attenuated cardiac dysfunction by modulating the expression of proteins involved in ketone body and fatty acid metabolism, and induction of UPRmt; this was likely mediated by activation of the SIRT3-AMPK pathway. Taken together, these results identify SIRT3-AMPK as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to cardiac stress. Choline treatment may represent a new therapeutic strategy for optimizing myocardial metabolism in the context of hypertrophy and heart failure.

[Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

Comparison of T lymphocyte subsets in aplastic anemia and hypoplastic myelodysplastic syndromes.

AIMS: This study aims to compare the proportion of peripheral blood T lymphocyte subsets and related blood cell and bone marrow cytology indexes between patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS), and investigate the clinical identification significance. MATERIALS AND METHODS: A total of 41 patients with AA and 46 patients with hypo-MDS were collected, and the proportions of peripheral blood T lymphocyte subsets, CD3-CD16/CD56+NK cells, CD3+CD57+T-LGL cells and CD19+B lymphocytes were detected by flow cytometry. KEY FINDINGS: The CD4+/CD8+ ratio decreased in the AA and hypo-MDS groups, and the difference was statistically significant when compared with that in the control group (P<0.05). However, there was no significant difference between AA and hypo-MDS groups (P>0.05). The proportions of CD3-CD16/CD56+NK cells and CD3+CD57+T-LGL cells in the hypo-MDS group were distinctly higher than those in the AA group (P<0.05). However, the proportion of CD19+B lymphocyte was obviously lower than that in the AA group (P<0.05). Furthermore, the proportions of reticulocytes, bone marrow progenitor cells and immature red blood cells in the hypo-MDS group were significantly more than those in the AA group (P<0.05), and the proportion of mature lymphocytes in the hypo-MDS group was distinctly lower than that in the AA group (P<0.05). SIGNIFICANCE: Changes of T lymphocyte subsets and the proportions of large granular lymphocytes and B lymphocytes can be utilized as indexes in the differential diagnosis between AA and hypo-MDS.

Vagal nerve stimulation improves mitochondrial dynamics via an M3 receptor/CaMKKß/AMPK pathway in isoproterenol-induced myocardial ischaemia.

Mitochondrial dynamics-fission and fusion-are associated with ischaemic heart disease (IHD). This study explored the protective effect of vagal nerve stimulation (VNS) against isoproterenol (ISO)-induced myocardial ischaemia in a rat model and tested whether VNS plays a role in preventing disorders of mitochondrial dynamics and function. Isoproterenol not only caused cardiac injury but also increased the expression of mitochondrial fission proteins [dynamin-related peptide1 (Drp1) and mitochondrial fission protein1 (Fis-1)) and decreased the expression of fusion proteins (optic atrophy-1 (OPA1) and mitofusins1/2 (Mfn1/2)], thereby disrupting mitochondrial dynamics and leading to increase in mitochondrial fragments. Interestingly, VNS restored mitochondrial dynamics through regulation of Drp1, Fis-1, OPA1 and Mfn1/2; enhanced ATP content and mitochondrial membrane potential; reduced mitochondrial permeability transition pore (MPTP) opening; and improved mitochondrial ultrastructure and size. Furthermore, VNS reduced the size of the myocardial infarction and ameliorated cardiomyocyte apoptosis and cardiac dysfunction induced by ISO. Moreover, VNS activated AMP-activated protein kinase (AMPK), which was accompanied by phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinase ß (CaMKKß) during myocardial ischaemia. Treatment with subtype-3 of muscarinic acetylcholine receptor (M3 R) antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide or AMPK inhibitor Compound C abolished the protective effects of VNS on mitochondrial dynamics and function, suggesting that M3 R/CaMKKß/AMPK signalling are involved in mediating beneficial effects of VNS. This study demonstrates that VNS modulates mitochondrial dynamics and improves mitochondrial function, possibly through the M3 R/CaMKKß/AMPK pathway, to attenuate ISO-induced cardiac damage in rats. Targeting mitochondrial dynamics may provide a novel therapeutic strategy in IHD.

Analysis of anti-depressant potential of curcumin against depression induced male albino wistar rats.

The present study investigated the antidepressant potential of curcumin in olfactory bulbectomy and forced swimming test models of depression in male albino rats under chronic treatment. The experimental animals were divided into four groups, and curcumin was administered for 45 days. Our results showed that the curcumin significantly reduced olfactory bulbectomy-induced behavioral abnormalities including deficits in step-down passive avoidance, increased activity in the open area and immobility time. Chronic administration of curcumin significantly reversed levels of 3, 4-dihydroxyphenylacetic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid in the hippocampus region of male albino rats. Also, curcumin normalizes the levels of dopamine, noradrenaline, and 5-hydroxyindoleacetic acid in the frontal cortex of rats. Taking all these results together, it may suggest that curcumin is potent compound acting against the depression in the male albino rats.

Acetylcholine Attenuates Hypoxia/Reoxygenation Injury by Inducing Mitophagy Through PINK1/Parkin Signal Pathway in H9c2 Cells.

Acetylcholine (ACh) protected against cardiac injury via promoting autophagy and mitochondrial biogenesis, however, the involvement of mitophagy in ACh-elicited cardioprotection remains unknown. In the present study, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) and ACh treatment during reoxygenation. Mitophagy markers PTEN-induced kinase 1 (PINK1) and Parkin translocation were examined using western blot and confocal fluorescence microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) were detected with fluorescence staining. We found that H/R-treated cells exhibited reduced levels of PINK1 and Parkin in mitochondria, accompanied with decreased autophagy flux (reduced LC3-II/LC3-I and increased p62). Conversely, ACh increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy proteins. Confocal imaging of Parkin and MitoTracker Green-labeled mitochondria further confirmed ACh-induced mitochondrial translocation of Parkin, which was reversed by M2 receptor antagonist methoctramine and M2 receptor siRNA, suggesting ACh could induce mitophagy by M2 receptor after H/R. Mitophagy inhibitor 3-methaladenine abolished ACh-induced mitoprotection, manifesting as aggravated mitochondrial morphology disruption, ATP and membrane potential depletion, increased ROS overproduction, and apoptosis. Furthermore, PINK1/Parkin siRNA attenuated the protective effects of ACh against ATP loss and oxidative stress due to mitochondrial-dependent injury. Taken together, ACh promoted mitochondrial translocation of PINK1/Parkin to stimulate cytoprotective mitophagy via M2 receptor, which may provide beneficial targets in the preservation of cardiac homeostasis against H/R injury.