Characterization of aroma characteristics of silver carp mince glycated with different reducing sugars.

The purpose of this study was to investigate the volatile flavor changes in silver carp mince (SCM) gel glycated with different reducing sugars (glucose, L-arabinose, and xylose) based on E-nose, GC-IMS, and sensory evaluation. These results showed that glycation reduced the fishy smell of SCM gel and increased the meaty, toasty, and burnt smell. A total of 10 volatile compounds were considered as characteristic flavor compounds and potential markers. Among them, the main contributors of fishy included hexanal, heptanal, n-nonanal, octanal, etc. Toasty and burnt were mainly related to the production of 3-methylbutanal and furfurol. These results heralded that glycation could be used to improve the volatile flavor of SCM. This research provided a theoretical basis and technical support for glycation in aquatic food flavor quality control, aquatic pre-made food development, and aquatic leisure food processing.

[Investigation on the signaling pathways in the mechanism of hyperoxia-induced acute lung injury based on transcriptomics sequencing].

OBJECTIVE: To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI. METHODS: Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis. RESULTS: Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2-ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/ß-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2-ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/ß-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2-ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/ß-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2-ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/ß-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2-ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/ß-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. CONCLUSIONS: HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Enhancement mechanism of glycation with l-arabinose and xylose on texture properties of silver carp mince gel.

BACKGROUND: Glycation is a green processing technology. Based on our previous studies, glycation with l-arabinose and xylose was beneficial to enhance the texture properties of silver carp mince (SCM) gels. However, the possible enhancement mechanism remained unclear. Therefore, in this study, SCM gels with different types of reducing sugar (glucose, l-arabinose, and xylose) were prepared based on our previous study. The possible mechanism of texture enhancement of SCM gels was analyzed by investigating the changes in water distribution, protein structures, and microstructure in the gel system. RESULTS: The glycation of l-arabinose and xylose enhanced the hardness, cohesiveness, chewiness, and resilience of SCM gels. Hardness increased from 1883.04 (control group) to 3624.54 (l-arabinose group) and 4348.18 (xylose group). Low-field nuclear magnetic resonance (LF-NMR) showed that glycation promoted the tight binding of immobilized water to proteins. Raman spectroscopic analysis showed that glycation increased the surface hydrophobicity and promoted the formation of disulfide bonds. Scanning electron microscopy (SEM) showed that glycation promoted the formation of uniform and dense three-dimensional network structure in SCM gels. CONCLUSION: In summary, glycation enhanced the binding ability of immobilized water to proteins, improved the surface hydrophobicity, promoted the formation of disulfide bonds, and led to a more uniform and dense gel network structure of proteins, thus enhancing the texture properties of SCM gels. This research provided a theoretical basis for a better understanding of the mechanism of the effect of glycation on the quality of gel products and also provided technical support for the application of l-arabinose and xylose in new functional gel foods. © 2024 Society of Chemical Industry.

Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis.

Background: Hyperoxia-induced acute lung injury (HALI) is a complication to ventilation in patients with respiratory failure, which can lead to acute inflammatory lung injury and chronic lung disease. The aim of this study was to integrate bioinformatics analysis to identify key genes associated with HALI and validate their role in H2O2-induced cell injury model.Methods: Integrated bioinformatics analysis was performed to screen vital genes involved in hyperoxia-induced lung injury (HLI). CCK-8 and flow cytometry assays were performed to assess cell viability and apoptosis. Western blotting was performed to assess protein expression.Results: In this study, glycoprotein non-metastatic melanoma protein B (Gpnmb) was identified as a key gene in HLI by integrated bioinformatics analysis of 4 Gene Expression Omnibus (GEO) datasets (GSE97804, GSE51039, GSE76301 and GSE87350). Knockdown of Gpnmb increased cell viability and decreased apoptosis in H2O2-treated MLE-12 cells, suggesting that Gpnmb was a proapoptotic gene during HALI. Western blotting results showed that knockdown of Gpnmb reduced the expression of Bcl-2 associated X (BAX) and cleaved-caspase 3, and increased the expression of Bcl-2 in H2O2 treated MLE-12 cells. Furthermore, Gpnmb knockdown could significantly reduce reactive oxygen species (ROS) generation and improve the mitochondrial membrane potential.Conclusion: The present study showed that knockdown of Gpnmb may protect against HLI by repressing mitochondrial-mediated apoptosis.

A linear energy transfer distributions computation method for inhomogeneous medium by using the water equivalent ratio approximation.

Dose-averaged linear energy transfer (LET), LETd is widely used in proton therapy. Compared with analytical models, Monte Carlo (MC) simulations are more accurate in obtaining LETd distributions, but they are time-consuming. This study used the 3D LETd distributions of proton beam spots in water by MC simulations as a benchmark data set. Subsequently, by combining the water equivalent ratio of various human tissues, the 3D LETd distributions of clinical cases could be quickly obtained. Our method was applied to a single spot of 160 MeV proton beam in a water-bone phantom and a pelvic case. We also computed the 3D LETd distributions for multiple proton beam spots in the pelvic case and a lung case. The results of our method were compared with the results of MC simulations, demonstrating that our method can rapidly provide 3D LETd distributions of clinical cases with acceptable differences from MC simulations.

ANXA1sp attenuates sepsis-induced myocardial injury by promoting mitochondrial biosynthesis and inhibiting oxidative stress and autophagy via SIRT3 upregulation.

Sepsis-induced myocardial injury is one of the most difficult complications of sepsis in intensive care units. Annexin A1 (ANXA1) short peptide (ANXA1sp) protects organs during the perioperative period. However, the protective effect of ANXA1sp against sepsis-induced myocardial injury remains unclear. We aimed to explore the protective effects and mechanisms of ANXA1sp against sepsis-induced myocardial injury both in vitro and in vivo. Cellular and animal models of myocardial injury in sepsis were established with lipopolysaccharide. The cardiac function of mice was assessed by high-frequency echocardiography. Elisa assay detected changes in inflammatory mediators and markers of myocardial injury. Western blotting detected autophagy and mitochondrial biosynthesis-related proteins. Autophagic flux changes were observed by confocal microscopy, and autophagosomes were evaluated by TEM. ATP, SOD, ROS, and MDA levels were also detected.ANXA1sp pretreatment enhanced the 7-day survival rate, improved cardiac function, and reduced TNF-α, IL-6, IL-1ß, CK-MB, cTnI, and LDH levels. ANXA1sp significantly increased the expression of sirtuin-3 (SIRT3), mitochondrial biosynthesis-related proteins peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), and mitochondrial transcription factor A (TFAM). ANXA1sp increased mitochondrial membrane potential (△Ψm), ATP, and SOD, and decreased ROS, autophagy flux, the production of autophagosomes per unit area, and MDA levels. The protective effect of ANXA1sp decreased significantly after SIRT3 silencing in vitro and in vivo, indicating that the key factor in ANXA1sp's protective role is the upregulation of SIRT3. In summary, ANXA1sp attenuated sepsis-induced myocardial injury by upregulating SIRT3 to promote mitochondrial biosynthesis and inhibit oxidative stress and autophagy.

[Wedelolactone alleviates hyperoxia-induced acute lung injury by regulating ferroptosis].

OBJECTIVE: To study whether wedelolactone can reduce hyperoxia-induced acute lung injury (HALI) by regulating ferroptosis, and provide a basic theoretical basis for the drug treatment of HALI. METHODS: A total of 24 C57BL/6J mice were randomly divided into normal oxygen control group, HALI model group and wedelolactone pretreatment group, with 8 mice in each group. Mice in wedelolactone pretreatment group were treated with wedelolactone 50 mg/kg intraperitoneally for 6 hours, while the other two groups were not given with wedelolactone. After that, the HALI model was established by maintaining the content of carbon dioxide < 0.5% and oxygen > 90% in the molding chamber for 48 hours, and the normal oxygen control group was placed in indoor air. After modeling, the mice were sacrificed and lung tissues were collected. The lung histopathological changes were observed under light microscope and pathological scores were performed to calculate the ratio of lung wet/dry mass (W/D). The levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1ß), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in lung tissues of mice in each group were determined. The protein expression of glutathione peroxidase 4 (GPX4) in lung tissue was detected by Western blotting. RESULTS: Under light microscope, the alveolar structure of HALI model group was destroyed, and a large number of neutrophils infiltrated the alveolar and interstitial lung, and the interstitial lung was thickened. The pathological score of lung injury (score: 0.75±0.02 vs. 0.11±0.01) and the ratio of lung W/D (6.23±0.34 vs. 3.68±0.23) were significantly higher than those in the normal oxygen control group (both P < 0.05). Wedelolactone pretreated mice had clear alveolar cavity and lower neutrophil infiltration and interstitial thickness than HALI group. Pathological scores (score: 0.43±0.02 vs. 0.75±0.02) and W/D ratio (4.56±0.12 vs. 6.23±0.34) were significantly lower than HALI group (both P < 0.05). Compared with the normal oxygen control group, the levels of SOD (kU/g: 26.41±4.25 vs. 78.64±3.95) and GSH (mol/g: 4.51±0.33 vs. 12.53±1.25) in HALI group were significantly decreased, while the levels of MDA (mmol/g: 54.23±4.58 vs. 9.65±1.96), TNF-α (µg/L: 96.32±3.67 vs. 11.65±2.03), IL-6 (ng/L: 163.35±5.89 vs. 20.56±3.63) and IL-1ß (µg/L: 72.34±4.64 vs. 15.64±2.47) were significantly increased, and the protein expression of GPX4 (GPX4/ß-actin: 0.44±0.02 vs. 1.00±0.09) was significantly decreased (all P < 0.05). Compared with the HALI group, the levels of SOD (kU/g: 53.28±3.69 vs. 26.41±4.25) and GSH (mol/g: 6.73±0.97 vs. 12.53±1.25) were significantly higher in the wedelolactone pretreatment group, and the levels of MDA (mmol/g: 25.36±1.98 vs. 54.23±4.58), TNF-α (µg/L: 40.25±4.13 vs. 96.32±3.67), IL-6 (ng/L: 78.32±4.65 vs. 163.35±5.89), and IL-1ß (µg/L: 30.65±3.65 vs. 72.34±4.64) were significantly lower (all P < 0.05), and protein expression of GPX4 was significantly higher (GPX4/ß-actin: 0.68±0.04 vs. 0.44±0.02, P < 0.05). CONCLUSIONS: Wedelolactone attenuates HALI injury by regulating ferroptosis.

Hyperoxia can Induce Lung Injury by Upregulating AECII Autophagy and Apoptosis Via the mTOR Pathway.

Oxygen therapy is a crucial medical intervention, but it is undeniable that it can lead to lung damage. The mTOR pathway plays a pivotal role in governing cell survival, including autophagy and apoptosis, two phenomena deeply entwined with the evolution of diseases. However, it is unclarified whether the mTOR pathway is involved in hyperoxic acute lung injury (HALI). The current study aims to clarify the molecular mechanism underlying the pathogenesis of HALI by constructing in vitro and in vivo models using H2O2 and hyperoxia exposure, respectively. To investigate the role of mTOR, the experiment was divided into five groups, including normal group, injury group, mTOR inhibitor group, mTOR activator group, and DMSO control group. Western blotting, Autophagy double labeling, TUNEL staining, and HE staining were applied to evaluate protein expression, autophagy activity, cell apoptosis, and pathological changes in lung tissues. Our data revealed that hyperoxia can induce autophagy and apoptosis in Type II alveolar epithelial cell (AECII) isolated from the treated rats, as well as injuries in the rat lung tissues; also, H2O2 stimulation increased autophagy and apoptosis in MLE-12 cells. Noticeably, the experiments performed in both in vitro and in vivo models proved that the mTOR inhibitor Rapamycin (Rapa) functioned synergistically with hyperoxia or H2O2 to promote AECII autophagy, which led to increased apoptosis and exacerbated lung injury. On the contrary, activation of mTOR with MHY1485 suppressed autophagy activity, consequently resulting in reduced apoptosis and lung injury in H2O2-challenged MLE-12 cells and hyperoxia-exposed rats. In conclusion, hyperoxia caused lung injury via mTOR-mediated AECII autophagy.

ROS-mediated MAPK activation aggravates hyperoxia-induced acute lung injury by promoting apoptosis of type II alveolar epithelial cells via the STAT3/miR-21-5p axis.

Inhibition of type II alveolar epithelial (AE-II) cell apoptosis is a critical way to cure hyperoxia-induced acute lung injury (HALI). It has been reported that miR-21-5p could reduce H2O2-induced apoptosis in AE-II cells. However, the upstream molecular mechanism remains unclear. Herein, we established a cellular model of HALI by exposing AE-II cells to H2O2 treatment. It was shown that miR-21-5p alleviated H2O2-induced apoptosis in AE-II cells. ROS inhibition decreased apoptosis of H2O2-evoked AE-II cells via increasing miR-21-5p expression. In addition, ROS induced MAPK and STAT3 phosphorylation in H2O2-treated AE-II cells. MAPK inactivation reduces H2O2-triggered AE-II cell apoptosis. MAPK activation inhibits miR-21-5p expression by promoting STAT3 phosphorylation in H2O2-challenged AE-II cells. Furthermore, STAT3 activation eliminated MAPK deactivation-mediated inhibition on the apoptosis of AE-II cells under H2O2 condition. In conclusion, ROS-mediated MAPK activation promoted H2O2-triggered AE-II cell apoptosis by inhibiting miR-21-5p expression via STAT3 phosphorylation, providing novel targets for HALI treatment.

ANXA1sp Protects against Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis-Induced Cardiomyocyte Death via SIRT3-Mediated p53 Deacetylation.

Sepsis-induced myocardial injury (SIMI), a common complication of sepsis, may cause significant mortality. Ferroptosis, a cell death associated with oxidative stress and inflammation, has been identified to be involved in SIMI. This study sought to investigate the role of ANXA1 small peptide (ANXA1sp) in SIMI pathogenesis. In this study, the mouse cardiomyocytes (H9C2 cells) were stimulated with lipopolysaccharide (LPS) to imitate SIMI in vitro. It was shown that ANXA1sp treatment substantially abated LPS-triggered H9C2 cell death and excessive secretion of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6). ANXA1sp pretreatment also reversed the increase of ROS and MDA generation as well as the decrease of SOD and GSH activity in H9C2 cells caused by LPS treatment. In addition, ANXA1sp considerably eliminated LPS-caused H9C2 cell ferroptosis, as revealed by the suppression of iron accumulation and the increase in GPX4 and FTH1 expression. Furthermore, the ameliorative effects of ANXA1sp on LPS-induced H9C2 cell damage could be partially abolished by erastin, a ferroptosis agonist. ANXA1sp enhanced SIRT3 expression in LPS-challenged H9C2 cells, thereby promoting p53 deacetylation. SIRT3 knockdown diminished ANXA1sp-mediated alleviation of cell death, inflammation, oxidative stress, and ferroptosis of LPS-treated H9C2 cells. Our study demonstrated that ANXA1sp is protected against LPS-induced cardiomyocyte damage by inhibiting ferroptosis-induced cell death via SIRT3-dependent p53 deacetylation, suggesting that ANXA1sp may be a potent therapeutic agent for SIMI.

[MicroRNA21-5p alleviates hyperoxia-induced acute lung injury in rats through activating phosphatidylinositol 3 kinase/serine-threonine protein kinase signaling pathway by regulating type II alveolar epithelial cell apoptosis].

OBJECTIVE: To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type II alveolar epithelial cell (AEC II). METHODS: Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 µL titer (1×1012 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AEC II cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. RESULTS: Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AEC II cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AEC II cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AEC II cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (µg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1ß (µg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AEC II cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg ≈ 0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2-ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AEC II cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. CONCLUSIONS: miR-21-5p attenuates HALI by inhibiting AEC II cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.

Phloroglucinol inhibits oxytocin-induced contraction in rat gastric circular muscle and uterine smooth muscle.

Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. In this study, a PD rat model was established. The effects of phloroglucinol on the contraction of rat gastric circular muscle and uterine smooth muscle induced by oxytocin (OT) were investigated. The writhing response, and levels of oestradiol (E2), prostaglandin e2 (PGE2), and prostaglandin f2α (PGF2α) were determined. The protein and mRNA levels of OT receptor (OTR) were detected. OT showed a significant promoting effect on gastric circular muscle and uterine smooth muscle contraction. However, phloroglucinol strongly inhibited the contraction induced by 10-6 mol/L of OT. We also found that phloroglucinol reduced writhing response and attenuated uterine damage. Compared to the blank group, E2 and PGF2α were significantly increased, but PGE2 was significantly decreased in the PD model group. Phloroglucinol was found to reverse the changes of E2, PGF2α and PGE2. Moreover, phloroglucinol reduced the protein and mRNA levels of OTR. In conclusion, phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The mechanism might be related with the regulation of OTR expression.IMPACT STATEMENTWhat is already known on this subject? Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development.What do the results of this study add? Phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The underlying mechanisms of phloroglucinol for PD treatment may be associated with OTR.What are the implications of these findings for clinical practice and/or further research? These findings provide novel ideas for the role of phloroglucinol in PD development.

Annexin-A1 short peptide alleviates septic myocardial injury by upregulating SIRT3 and inhibiting myocardial cell apoptosis.

Septic myocardial injury is a common complication of severe sepsis, which occurs in about 50% of cases. Patients with this disease may experience varying degrees of myocardial damage. Annexin-A1 short peptide (ANXA1sp), with a molecular structure of Ac-Gln-Ala-Tyr, has been reported to exert an organ protective effect in the perioperative period by modulating sirtuin-3 (SIRT3). Whether it possesses protective activity against sepsis-induced cardiomyopathy is worthy of study. This study aimed to investigate whether ANXA1sp exerts its anti-apoptotic effect in septic myocardial injury in vitro and in vivo via regulating SIRT3. In this study, we established in vivo and in vivo models of septic myocardial injury based on C57BL/6 mice and primary cardiomyocytes by lipopolysaccharide (LPS) induction. Results showed that ANXA1sp pretreatment enhanced the seven-day survival rate, improved left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and cardiac output (CO), and reduced the levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Western blotting results revealed that ANXA1sp significantly increased the expression of SIRT3, Bcl-2, and downregulated Bax expression. TUNEL staining and flow cytometry results showed that ANXA1sp could attenuate the apoptosis rate of cardiomyocytes, whereas this anti-apoptotic effect was significantly attenuated after SIRT3 knockout. To sum up, ANXA1sp can alleviate LPS-induced myocardial injury by reducing myocardial apoptosis via SIRT3 upregulation.

Physicochemical properties and gel-forming ability changes of duck myofibrillar protein induced by hydroxyl radical oxidizing systems.

This paper focuses on the changes of physicochemical properties and gel-forming ability of duck myofibrillar proteins (DMPs) induced using hydroxyl radical oxidizing systems. DMPs were firstly extracted and then oxidized at various H2O2 concentrations (0, 4, 8, and 12 mmol/L) using Fenton reagent (Fe3+-Vc-H2O2) to generate hydroxyl radicals, and the effects of hydroxyl radical oxidation on the physicochemical changes and heat-induced gel-forming capacity of DMPs were analyzed. We observed obvious increases in the carbonyl content (p < 0.05) and surface hydrophobicity of DMPs with increasing of H2O2 concentrations (0-12 mmol/L). In contrast, the free thiol content (p < 0.05) and water retention ability of DMPs decreased with increasing H2O2 concentrations (0-12 mmol/L). These physicochemical changes suggested that high concentrations of hydroxyl radicals significantly altered the biochemical structure of DMPs, which was not conducive to the formation of a gel mesh structure. Furthermore, the gel properties were reduced based on the significant decrease in the water holding capacity (p < 0.05) and increased transformation of immobilized water of the heat-induced gel to free water (p < 0.05). With the increase of H2O2 concentrations, secondary structure of proteins analysis results indicated α-helix content decreased significantly (p < 0.05), however, random coil content increased (p < 0.05). And more cross-linked myosin heavy chains were detected at higher H2O2 concentrations groups through immunoblot analysis (p < 0.05). Therefore, as H2O2 concentrations increased, the gel mesh structure became loose and porous, and the storage modulus and loss modulus values also decreased during heating. These results demonstrated that excessive oxidation led to explicit cross-linking of DMPs, which negatively affected the gel-forming ability of DMPs. Hence, when processing duck meat products, the oxidation level of meat gel products should be controlled, or suitable antioxidants should be added.

Effect of Malondialdehyde-Induced Oxidation Modification on Physicochemical Changes and Gel Characteristics of Duck Myofibrillar Proteins.

This paper focuses on the effect of malondialdehyde-induced oxidative modification (MiOM) on the gel properties of duck myofibrillar proteins (DMPs). DMPs were first prepared and treated with oxidative modification at different concentrations of malondialdehyde (0, 0.5, 2.5, 5.0, and 10.0 mmol/L). The physicochemical changes (carbonyl content and free thiol content) and gel properties (gel whiteness, gel strength, water holding capacity, rheological properties, and microstructural properties) were then investigated. The results showed that the content of protein carbonyl content increased with increasing MDA oxidation (p < 0.05), while the free thiol content decreased significantly (p < 0.05). Meanwhile, there was a significant decrease in gel whiteness; the gel strength and water-holding capacity of protein gels increased significantly under a low oxidation concentration of MDA (0−5 mmol/L); however, the gel strength decreased under a high oxidation concentration (10 mmol/L) compared with other groups (0.5−5 mmol/L). The storage modulus and loss modulus of oxidized DMPs also increased with increasing concentrations at a low concentration of MDA (0−5 mmol/L); moreover, microstructural analysis confirmed that the gels oxidized at low concentrations (0.5−5 mmol/L) were more compact and homogeneous in terms of pore size compared to the high concentration or blank group. In conclusion, moderate oxidation of malondialdehyde was beneficial to improve the gel properties of duck; however, excessive oxidation was detrimental to the formation of dense structured gels.

[Role and mechanism of signal transducer and activator of transcription protein STAT1/3/5 in hyperoxia-induced acute lung injury].

OBJECTIVE: To investigate whether signal transducer and activator of transcription (STAT1/3/5) have a protective effect on hyperoxia-induced acute lung injury (HALI) and its mechanism. METHODS: Seventy C57BL/6J mice were randomly divided into five groups: normoxia control group, HALI group, and STAT1/3/5 inhibitor groups, with 14 mice in each group. The HALI model was established by exposure to more than 90% hyperoxia for 48 hours; three STAT inhibitor groups were pretreated by intraperitoneal injection of STAT1 inhibitor 40 mg/kg and STAT3 inhibitor 5 mg/kg, and STAT5 inhibitor 10 mg/kg for 1 week. Six blood samples were randomly collected from each group, and microRNA-21 (miR-21) expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Lung tissue of the sacrificed mice was obtained, and enzyme linked immunosorbent assay (ELISA) was used to detect the contents of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1ß), superoxide dismutase (SOD), malonic dialdehyde (MDA), and matrix metalloproteinase 9 (MMP9). The water content of lung tissue was calculated. The pathological changes in lung tissue were observed under the light microscope, and the pathological score of lung injury was performed. Western blotting was used to detect the expression of phosphorylated STAT (p-STAT1, p-STAT3, p-STAT5) in lung tissue. The 7-day cumulative survival rates of the remaining 8 mice in each group were analyzed using Kaplan-Meier survival curves. RESULTS: Under the light microscope, the alveolar structures in the HALI group and the STAT1 inhibitor group were destroyed, a large number of neutrophils (NEU) infiltrated in the alveoli and lung interstitium, which were thickened. The pathological score of lung injury and the water content of the lung tissue was significantly increased. In STAT3 inhibitor and STAT5 inhibitor groups, the alveolar cavity was clear, the degree of NEU infiltration and the thickness of lung interstitium were lower than those in HALI group, the pathological score of lung injury and the water content of lung tissue were significantly decreased, especially in STAT3 inhibitor group. Compared with the normoxia control group, the contents of TNF-α, IL-6, IL-1ß, MDA, and MMP9, and the expression levels of p-STAT3 and p-STAT5 in the HALI group were significantly increased. In contrast, the content of SOD and the expression of miR-21 were significantly decreased. Compared with the HALI group, the contents of TNF-α, IL-6, IL-1ß, MDA, and MMP9 in the STAT3 inhibitor group and STAT5 inhibitor group were significantly decreased. At the same time, the content of SOD and the expression of miR-21 were significantly increased, especially in STAT3 inhibitor group [TNF-α (µg/L): 42.53±3.25 vs. 86.36±5.48, IL-6 (ng/L): 68.46±4.28 vs. 145.00±6.89, IL-1ß (µg/L): 28.74±3.53 vs. 68.00±5.64, MDA (µmol/g): 20.33±2.74 vs. 42.58±3.45, and MMP9 (ng/L): 128.55±6.35 vs. 325.13±6.65, SOD (kU/g): 50.53±4.19 vs. 22.53±3.27, miR-21 (2-ΔΔCt): 0.550±0.018 vs. 0.316±0.037, all P < 0.05]. Kaplan-Meier survival curve analysis showed that the 7-day cumulative survival rates of the STAT3 inhibitor group and STAT5 inhibitor group were significantly higher than those of the HALI group [62.5% (5/8), 37.5% (3/8) vs. 12.5% (1/8), both P < 0.05]. CONCLUSIONS: Inhibition of STAT3 hyperactivation may suppress the inflammatory response, regulate oxidative stress, improve lung permeability through regulating the expression of miR-21, which exert lung protection in HALI.

DTX-P7, a peptide-drug conjugate, is highly effective for non-small cell lung cancer.

Despite tremendous success of molecular targeted therapy together with immunotherapy, only a small subset of patients can benefit from them. Chemotherapy remains the mainstay treatment for most of tumors including non-small cell lung cancer (NSCLC); however, non-selective adverse effects on healthy tissues and secondary resistance are the main obstacles. Meanwhile, the quiescent or dormant cancer stem-like cells (CSLCs) are resistant to antimitotic chemoradiotherapy. Complete remission can only be realized when both proliferative cancer cells and quiescent cancer stem cells are targeted. In the present research, we constructed a cooperatively combating conjugate (DTX-P7) composed of docetaxel (DTX) and a heptapeptide (P7), which specifically binds to cell surface Hsp90, and assessed the anti-tumor effects of DTX-P7 on non-small cell lung cancer. DTX-P7 preferentially suppressed tumor growth compared with DTX in vivo with a favorable distribution to tumor tissues and long circulation half-life. Furthermore, we revealed a distinctive mechanism whereby DTX-P7 induced unfolded protein response and eventually promoted apoptosis. More importantly, we found that DTX-P7 promoted cell cycle reentry of slow-proliferating CSLCs and subsequently killed them, exhibiting a "proliferate to kill" pattern. Collecitvely, by force of active targeting delivery of DTX via membrane-bound Hsp90, DTX-P7 induces unfolded protein response and subsequent apoptosis by degrading Hsp90, meanwhile awakens and kills the dormant cancer stem cells. Thus, DTX-P7 deserves further development as a promising anticancer therapeutic for treatment of various membrane-harboring Hsp90 cancer types.

Effect of glycation on physicochemical properties and volatile flavor characteristics of silver carp mince.

The purpose of this study was to explore the effect of glycation on physicochemical properties and volatile flavor characteristics of silver carp mince (SCM). The changes in the degree of grafting, chemical composition, pH, color, total amino acid composition, and volatile flavor compounds of SCM with or without glucose were studied at different heating times. The results showed that the addition of glucose could promote the glycation reaction rate of SCM. Lysine and cysteine were the main amino acids involved in glycation. Glycation enhanced the overall aroma of SCM by accelerating lipid oxidation and Strecker degradation. In conclusion, these results suggest that glycation can enhance the volatile flavor of SCM during thermal processing and can be used as a volatile flavor enhancement technology for the development of protein nutrition food with good flavor from low-value fish.

Comparison of different edible parts of bighead carp (Aristichthys nobilis) flavor.

The study aims to obtain the information on taste and odor among different edible parts (white dorsal meat, white abdomen meat, white tail meat, and dark meat) of bighead carp. The results showed that the white dorsal meat and white abdomen meat had the higher content of total amino acids among all edible parts of bighead carp samples. The highest inosine monophosphate and adenosine monophosphate content presented in white abdomen meat, and the highest equivalent umami concentration value presented in dark meat. The principal component analysis result of electronic tongue and electronic nose showed significant differences in the overall taste and odor characteristics among four group samples. Additionally, 41, 30, 42, and 29 volatile compounds were identified by headspace solid-phase microextraction/gas chromatography-mass spectrometry among white dorsal meat, white abdomen meat, white tail meat, and dark meat of bighead carp, respectively. Based on the data of relative olfactory activity value (ROAV ≥ 1), 12 relative olfactory activity compounds may mainly contribute to the overall odor of bighead carp, including 2-methylbutanal, hexanal, heptanal, (E)-2-octenal, nonanal, dodecanal, undecanal, decanal, 3-methyl-1-pentanol, 1-octen-3-ol, (Z)-2-octen-1-ol, and eucalyptol. Furthermore, according to the Partial Least Squares Discriminant Analysis profile derived from the ROAV of 12 characteristic volatile compounds, significant variations in the odor of different edible parts of bighead carp. Overall, there was a significant difference in taste and odor among different edible parts of bighead carp, and this study may provide useful information for unraveling the flavor characteristics of each edible part of raw bighead carp. PRACTICAL APPLICATIONS: The comprehensive information on taste and odor among different edible parts (white dorsal meat, white abdomen meat, white tail meat, and dark meat) of bighead carp were obtained using liquid chromatography-mass spectrometry, automatic amino acid analyzer, electronic tongue (E-tongue), headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS), and electronic nose (E-tongue), respectively. This study may provide useful information for unraveling the flavor characteristics of each edible part of raw bighead carp and improving the flavor of bighead carp products.