Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Comparing different postoperative sedation strategies for patients in the intensive care unit after cardiac surgery: A systematic review of randomized controlled trials and network meta-analysis.

BACKGROUND: Various postoperative sedation protocols with different anaesthetics lead to profound effects on the outcomes for post-cardiac surgery patients. However, a comprehensive analysis of optimal postoperative sedation strategies for patients in the intensive care unit (ICU) after cardiac surgery is lacking. METHODS: We systematically searched for randomized controlled trials (RCTs) in databases including PubMed and Embase. The primary outcome measured the duration of mechanical ventilation (MV) in the ICU, and the secondary outcome encompassed the length of stay (LOS) in the ICU and hospital and the monitoring adverse events. RESULTS: The literature included 18 RCTs (1652 patients) with 13 sedation regimens. Dexmedetomidine plus ketamine and sevoflurane were associated with a significantly reduced duration of MV when compared with propofol. Our results also suggested that dexmedetomidine plus ketamine may associated with a shorter LOS in ICU, and sevoflurane associated with a shorter LOS in the hospital, respectively. CONCLUSIONS: The combination of dexmedetomidine and ketamine seems to be a better option for adult patients needing sedation after cardiac surgery, and the incidence of side effects is lower with dexmedetomidine. These findings have potential implications for medication management in the perioperative pharmacotherapy of cardiac surgery patients.

RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway.

BACKGROUND: RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. AIMS: We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms. METHODS: The expression of RBM3 in cSCC tissues and A431 cells was determined via immunohistochemistry and western blotting. Plenti-CMV-RBM3- Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting. RESULTS: RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway. CONCLUSION: This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.

Overcoming cancer drug-resistance calls for novel strategies targeting abnormal alternative splicing.

Abnormal gene alternative splicing (AS) events are strongly associated with cancer progression. Here, we summarize AS events that contribute to the development of drug resistance and classify them into three categories: alternative cis-splicing (ACS), alternative trans-splicing (ATS), and alternative back-splicing (ABS). The regulatory mechanisms underlying AS processes through cis-acting regulatory elements and trans-acting factors are comprehensively described, and the distinct functions of spliced variants, including linear spliced variants derived from ACS, chimeric spliced variants arising from ATS, and circRNAs generated through ABS, are discussed. The identification of dysregulated spliced variants, which contribute to drug resistance and hinder effective cancer treatment, suggests that abnormal AS processes may together serve as a precise regulatory mechanism enabling drug-resistant cancer cell survival or, alternatively, represent an evolutionary pathway for cancer cells to adapt to changes in the external environment. Moreover, this review summarizes recent advancements in treatment approaches targeting AS-associated drug resistance, focusing on cis-acting elements, trans-acting factors, and specific spliced variants. Collectively, gaining an in-depth understanding of the mechanisms underlying aberrant alternative splicing events and developing strategies to target this process hold great promise for overcoming cancer drug resistance.

Self-degradable photosensitizer exhibiting bacterial agglutination and membrane insertion toward safe photodynamic ablation.

Self-oxidative degradation photosensitizers capable of bacterial agglutination and membrane insertion were fabricated based on a simple co-assembly strategy, for efficiently killing P. aeruginosa and rapidly deactivating their function post-treatment.

Metabolomic screening of radioiodine refractory thyroid cancer patients and the underlying chemical mechanism of iodine resistance.

Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.

New insights into the roles of Irisin in diabetic cardiomyopathy and vascular diseases.

Diabetes mellitus (DM) is a prevalent chronic disease in the 21st century due to increased lifespan and unhealthy lifestyle choices. Extensive research indicates that exercise can play a significant role in regulating systemic metabolism by improving energy metabolism and mitigating various metabolic disorders, including DM. Irisin, a well-known exerkine, was initially reported to enhance energy expenditure by indicating the browning of white adipose tissue (WAT) through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling. In this review, we summarize the potential mechanisms underlying the beneficial effects of Irisin on glucose dysmetabolism, including reducing gluconeogenesis, enhancing insulin energy expenditure, and promoting glycogenesis. Additionally, we highlight Irisin's potential to improve diabetic vascular diseases by stimulating nitric oxide (NO) production, reducing oxidative and nitrosative stress, curbing inflammation, and attenuating endothelial cell aging. Furthermore, we discuss the potential of Irisin to improve diabetic cardiomyopathy by preventing cardiomyocyte loss and reducing myocardial hypertrophy and fibrosis. Given Irisin's promising functions in managing diabetic cardiomyopathy and vascular diseases, targeting Irisin for therapeutic purposes could be a fruitful avenue for future research and clinical interventions.

Irisin attenuates ventilator-induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK.

Mechanical ventilation (MV) is an essential life-saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator-induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague-Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross-sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

Development of aptamer surface-enhanced Raman spectroscopy sensor based on Fe3O4@Pt and Au@Ag nanoparticles for the determination of acetamiprid.

As a common chlorinated nicotinic pesticide with high insecticidal activity, acetamiprid has been widely used for pest control. However, the irrational use of acetamiprid will pollute the environment and thus affect human health. Therefore, it is crucial to develop a simple, highly sensitive, and rapid method for acetamiprid residue detection. In this study, the capture probe (Fe3O4@Pt-Aptamer) was connected with the signal probe (Au@DTNB@Ag CS-cDNA) to form an assembly with multiple SERS-enhanced effects. Combined with magnetic separation technology, a SERS sensor with high sensitivity and stability was constructed to detect acetamiprid residue. Based on the optimal conditions, the SERS intensity measured at 1333 cm-1 is in relation to the concentration of acetamiprid in the range 2.25 × 10-9-2.25 × 10-5 M, and the calculated limit of detection (LOD) was 2.87 × 10-10 M. There was no cross-reactivity with thiacloprid, clothianidin, nitenpyram, imidacloprid, and chlorpyrifos, indicating that this method has good sensitivity and specificity. Finally, the method was applied to the detection of acetamiprid in cucumber samples, and the average recoveries were 94.19-103.58%, with RSD < 2.32%. The sensor can be used to analyse real samples with fast detection speed, high sensitivity, and high selectivity.

Health risk assessment of soil heavy metals in a typical mining town in north China based on Monte Carlo simulation coupled with Positive matrix factorization model.

The accumulation of heavy metals (HMs) in soil caused by mineral resource exploitation and its ancillary industrial processes poses a threat to ecology and public health. Effective risk control measures require a quantification of the impacts and contributions to health risks from individual sources of soil HMs. Based on high-density sampling, soil contamination risk indexes, positive matrix factorization (PMF) model, Monte Carlo simulation and human health risk analysis model were applied to investigate the risk of HMs in a typical mining town in North China. The results showed that As was the most dominant soil pollutant factor, Cd and Hg were the most dominant soil ecological risk factors, and Cr and Ni were the most dominant health risk factors in the study area. Overall, both pollution and ecological risks were at low levels, while there were still some higher hazard areas located in the central and south-central part of the region. According to the probabilistic health risk assessment (HRA), children suffered greater health risks than adults, with 21.63% of non-carcinogenic risks and 53.24% of carcinogenic risks exceeding the prescribed thresholds (HI > 1 and TCR>1E-4). The PMF model identified five potential sources: fuel combustion (FC), processing of building materials with limestone as raw materials (PBML), industry source (IS), iron ore mining combined with garbage (IOG), and agriculture source (AS). PBML is the primary source of soil HM contamination, as well as the major anthropogenic source of carcinogenic risk for all populations. Agricultural inputs associated with As are the major source of non-carcinogenic risk. This study offers a good example of probabilistic HRA using specific sources, which can provide a valuable reference for strategy establishment of pollution remediation and risk prevention and control.

TXNIP/NLRP3 aggravates global cerebral ischemia-reperfusion injury-induced cognitive decline in mice.

Global cerebral ischemia/reperfusion (GCI/R) injury poses a risk for cognitive decline, with neuroinflammation considered pivotal in this process. This study aimed to unravel the molecular mechanisms underlying GCI/R injury and propose a potential therapeutic strategy for associated cognitive deficits. Utilizing bioinformatics analysis of a public microarray profile (GSE30655 and GSE80681) in cerebral ischemic mice, it was observed that neuroinflammation emerged as a significant gene ontology item, with an increase in the expression of thioredoxin-interacting protein (TXNIP) and NLRP3 genes. Experimental models involving bilateral occlusion of the common carotid arteries in mice revealed that GCI/R induced cognitive impairment, along with a time-dependent increase in TXNIP and NLRP3 levels. Notably, TXNIP knockdown alleviated cognitive dysfunction in mice. Furthermore, the introduction of adeno-associated virus injection with TXNIP knockdown reduced the number of activated microglia, apoptosis neurons, and levels of oxidative stress and inflammatory cytokines in the hippocampus. Collectively, these findings underscore the significance of TXNIP/NLRP3 in the hippocampus in exacerbating cognitive decline due to GCI/R injury, suggesting that TXNIP knockdown holds promise as a therapeutic strategy.

A biodegradable oxidized starch/carboxymethyl chitosan film coated with pesticide-loaded ZIF-8 for tomato fusarium wilt control.

Film mulching is one of the most important methods to control soil-borne diseases. However, the traditional mulch may cause microplastic pollution and soil ecological damage. Herein, a biodegradable film was developed using oxidized starch and carboxymethyl chitosan and incorporated ZIF-8 carrying fludioxonil to sustainably control soil-borne disease. The microstructure, mechanical properties, optical properties, and water barrier properties of the composite films (Flu@ZIF-8-OS/CMCS) were investigated. The results show that Flu@ZIF-8-OS/CMCS had a smooth and uniform surface and excellent light transmittance. The excellent mechanical properties of the films were verified by tensile strength, elongation at break and Young's modulus. Higher contact angle and lower water vapor permeability indicate water retention capacity of the soil was improved through using Flu@ZIF-8-OS/CMCS. Furthermore, the release properties, biological activity, degradability and safety to soil organisms of Flu@ZIF-8-OS/CMCS was determined. The addition of ZIF-8 significantly improved the film's ability to retard the release of Flu, while the Flu@ZIF-8-OS/CMCS has good soil degradability. In vitro antifungal assays and pot experiments demonstrated excellent inhibitory activity against Fusarium oxysporum f. sp. Lycopersici. Flu@ZIF-8-OS/CMCS caused only 13.33 % mortality of earthworms within 7 d. This research provides a new approach to reducing microplastic pollution and effectively managing soil-borne diseases.

Construction and biological effects of a redox-enzyme dual-responsive lufenuron nano-controlled release formulation.

BACKGROUND: Pesticide formulations based on nanotechnology can effectively improve the efficiency of pesticide utilization and reduce pesticide residues in the environment. In this study, mesoporous silica nanoparticles containing disulfide bonds were synthesized by the sol-gel method, carboxylated and adsorbed with lufenuron, and grafted with cellulose to obtain a lufenuron-loaded nano-controlled release formulation (Luf@MSNs-ss-cellulose). RESULTS: The structure and properties of Luf@MSNs-ss-cellulose were characterized. The results showed that Luf@MSNs-ss-cellulose exhibits a regular spherical shape with 12.41% pesticide loading. The highest cumulative release rate (73.46%) of this pesticide-loaded nanoparticle was observed at 7 days in the environment of glutathione and cellulase, which shows redox-enzyme dual-responsive performance. As a result of cellulose grafting, Luf@MSNs-ss-cellulose had a small contact angle and high adhesion work on corn leaves, indicating good wetting and adhesion properties. After 14 days of spraying with 20 mg L-1 formulations in the long-term control efficacy experiment, the mortality of Luf@MSNs-ss-cellulose against Ostrinia furnacalis larvae (56.67%) was significantly higher than that of commercial Luf@EW (36.67%). Luf@MSNs-ss-cellulose is safer for earthworms and L02 cells. CONCLUSION: The nano-controlled release formulation obtained in this study achieved intelligent pesticide delivery in time and space under the environmental stimulation of glutathione and cellulase, providing an effective method for the development of novel pesticide delivery systems. © 2023 Society of Chemical Industry.

Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.

BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness. METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored. RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels. CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.

Research progress on the pathogenesis and treatment of ventilator-induced diaphragm dysfunction.

Prolonged controlled mechanical ventilation (CMV) can cause diaphragm fiber atrophy and inspiratory muscle weakness, resulting in diaphragmatic contractile dysfunction, called ventilator-induced diaphragm dysfunction (VIDD). VIDD is associated with higher rates of in-hospital deaths, nosocomial pneumonia, difficulty weaning from ventilators, and increased costs. Currently, appropriate clinical strategies to prevent and treat VIDD are unavailable, necessitating the importance of exploring the mechanisms of VIDD and suitable treatment options to reduce the healthcare burden. Numerous animal studies have demonstrated that ventilator-induced diaphragm dysfunction is associated with oxidative stress, increased protein hydrolysis, disuse atrophy, and calcium ion disorders. Therefore, this article summarizes the molecular pathogenesis and treatment of ventilator-induced diaphragm dysfunction in recent years so that it can be better served clinically and is essential to reduce the duration of mechanical ventilation use, intensive care unit (ICU) length of stay, and the medical burden.

A novel UVA-associated circUBE2I mediates ferroptosis in HaCaT cells.

Alternative splicing of precursor messenger RNA (pre-mRNA), including linear splicing and back splicing, produces multiple isoforms that lead to diverse cell fates in response to stimuli including ultraviolet radiation (UVR). Although UVR-induced linear gene splicing has been extensively studied in skin cells, the UVR-induced gene back-splicing events that lead to the production of circular RNAs (circRNAs) have not been thoroughly investigated. The present study used circRNA transcriptome sequencing to screen the differentially expressed circRNAs in human keratinocytes (HaCaT) after UVA irradiation. A total of 312 differentially expressed circRNAs were found in HaCaT cells post-UVR. Among the UVA-induced differentially expressed circRNAs, circUBE2I-a novel circRNA formed by exons 2-6 of the UBE2I gene-was the most significantly upregulated circRNA. RT-qPCR assay further confirmed the increase of circUBE2I level in HaCaT cells after UVA irradiation or H2 O2 treatment. RNase R digestion experiment revealed the stability of circUBE2I. Overexpression of circUBE2I in keratinocytes induced ferroptosis after UVA or H2 O2 , preventable by the ferroptosis inhibitor ferrostatin-1. Our study provides new insights into the role of circular RNAs in UVA-induced skin cell damage and suggests that circUBE2I could be a therapeutic target in UVR-aroused ferroptosis in skin cells.

The anticancer mechanisms of exopolysaccharide from Weissella cibaria D-2 on colorectal cancer via apoptosis induction.

Exopolysaccharide (EPS) from Weissella cibaria has been devoted to the study of food industry. However, the anticancer activity of W. cibaria derived EPS has not yet been investigated. In this study, we obtained the EPS from W. cibaria D-2 isolated from the feces of healthy infants and found that D-2-EPS, a homopolysaccharide with porous web like structure, could effectively inhibit the proliferation, migration, invasion and induce cell cycle arrest in G0/G1 phase of colorectal cancer (CRC) cells. In HT-29 tumor xenografts, D-2-EPS significantly retarded tumor growth without obvious cytotoxicity to normal organs. Furthermore, we revealed that D-2-EPS promoted the apoptosis of CRC cells by increasing the levels of Fas, FasL and activating Caspase-8/Caspase-3, indicating that D-2-EPS might induce apoptosis through the extrinsic Fas/FasL pathway. Taken together, the D-2-EPS has the potential to be developed as a nutraceutical or drug to prevent and treat colorectal cancer.

Exopolysaccharide from Weissella confusa J4-1 inhibits colorectal cancer via induction of cell cycle arrest.

Exopolysaccharide (EPS), a bioproduct of lactic acid bacteria (LAB), has various health-promoting biological activities that may be beneficial for cancer therapy. This in vivo and in vitro study aimed to elucidate the anti-colorectal cancer (CRC) capacity of a homopolysaccharide EPS obtained from Weissella confusa J4-1 (EPSJ4-1) isolated from the faeces of healthy infants. We confirmed that EPSJ4-1 contained glucose and effectively suppressed the proliferation, migration, and invasion of CRC cells. EPSJ4-1 treatment significantly retarded the growth of HT-29 tumour xenografts without causing cytotoxicity to normal organs. EPSJ4-1 exerts an inhibitory effect on cell proliferation by inducing G0/G1 phase cell cycle arrest in CRC cells. Furthermore, EPSJ4-1 upregulated p21 levels and downregulated mutant p53 and cyclin kinase 2 levels. This is the first study to demonstrate the antitumour effects of EPS from W. confusa on CRC via cell cycle arrest and inhibition of cell migration and invasion, suggesting that EPSJ4-1 has the potential to be developed as a nutraceutical or pharmaceutical drug to prevent and treat CRC.

The SIRT3 activator ganoderic acid D regulates airway mucin MUC5AC expression via the NRF2/GPX4 pathway.

PURPOSE: The expression of MUC5AC, a highly prevalent airway mucin, is regulated by stimulatory factors such as oxidative stress. Ganoderic acid D (GAD) activates mitochondrial deacetylase SIRT3. SIRT3 regulates mitochondrial function through deacetylation of mitochondrial proteins, thereby playing a significant role in alleviating oxidative stress-related diseases. Therefore, this study aimed to investigate the mechanisms and rationale underlying the regulation of MUC5AC expression by GAD. METHODS: Human airway epithelial cells (NCI-H292) were exposed to pyocyanin (PCN) to establish an in vitro cell model of airway mucus hypersecretion. The expression of SIRT3, MUC5AC, and NRF2 pathway proteins in cells was assessed. Cellular mitochondrial morphology and oxidative stress markers were analyzed. C57BL/6 mice were induced with Pseudomonas aeruginosa (PA) to establish an in vivo mouse model of airway mucus hypersecretion. The expression of SIRT3 and MUC5AC in the airways was examined. In addition, the differential expression of target genes in the airway epithelial tissues of patients with chronic obstructive pulmonary disease (COPD) was analyzed using publicly available databases. RESULTS: The results revealed a significant upregulation of MUC5AC expression and a significant downregulation of SIRT3 expression in relation to airway mucus hypersecretion. GAD inhibited the overexpression of MUC5AC in PCN-induced NCI-H292 cells and PA-induced mouse airways by upregulating SIRT3. GAD activated the NRF2/GPX4 pathway and inhibited PCN-induced oxidative stress and mitochondrial morphological changes in NCI-H292 cells. However, ML385 inhibited the regulatory effects of GAD on MUC5AC expression. CONCLUSION: The SIRT3 activator GAD downregulated MUC5AC expression, potentially through activation of the NRF2/GPX4 pathway. Accordingly, GAD may be a potential treatment approach for airway mucus hypersecretions.