Corticosterone Inhibits LPS-Induced NLRP3 Inflammasome Priming in Macrophages by Suppressing Xanthine Oxidase.

Following traumatic insult and associated pathogen infection, innate immunity is activated during the perioperative period, especially the NLRP3 inflammasome in macrophages. The neuroendocrine response is also rapidly activated to regulate excessive inflammation; however, the molecular mechanisms are still not completely clear. This study is aimed at investigating the modulation of NLRP3 inflammasome priming by endogenous glucocorticoids (corticosterone, CORT) and its relationship with xanthine oxidase (XO). RAW264.7 murine macrophages were stimulated with LPS (1 µg/ml). LPS-induced NLRP3 expression was pretreated by CORT at different concentrations (0-900 ng/ml). Then, the effect of higher concentrations of CORT (700 ng/ml) on LPS-induced NLRP3 expression and the effect of allopurinol (250 µg/ml) were observed. Finally, the effects of a CORT antagonist (RU486) on XO expression and activity and NLRP3 expression in macrophages were further analyzed. Supernatant levels IL-1ß and IL-18 were measured. The results showed that LPS-induced NLRP3 expression was upregulated further by pretreatment with CORT (300 ng/ml) (P < 0.05); however, higher concentrations of CORT (greater than 700 ng/ml) downregulated NLRP3 expression (P < 0.01) and the expression and activity of XO (P < 0.05 and P < 0.01, respectively). Allopurinol significantly inhibited NLRP3 expression. However, XO expression and activity, NLRP3 expression, and supernatant IL-1ß and IL-18 levels were significantly increased in the RU486 group compared with the CORT group. In conclusion, our results suggested that CORT inhibits LPS-induced NLRP3 inflammasome priming in macrophages. The underlying mechanism is related to the modulation of XO expression and activity, which may be involved in priming and activating the NLRP3 inflammasome.

Native tissue-based strategies for meniscus repair and regeneration.

Meniscus injuries appear to be becoming increasingly common and pose a challenge for orthopedic surgeons. However, there is no curative approach for dealing with defects in the inner meniscus region due to its avascular nature. Numerous strategies have been applied to regenerate and repair meniscus defects and native tissue-based strategies have received much attention. Native tissue usually has good biocompatibility, excellent mechanical properties and a suitable microenvironment for cellular growth, adhesion, redifferentiation, extracellular matrix deposition and remodeling. Classically, native tissue-based strategies for meniscus repair and regeneration are divided into autogenous and heterogeneous tissue transplantation. Autogenous tissue transplantation is performed more widely than heterogeneous tissue transplantation because there is no immunological rejection and the success rates are higher. This review first discusses the native meniscus structure and function and then focuses on the use of the autogenous tissue for meniscus repair and regeneration. Finally, it summarizes the advantages and disadvantages of heterogeneous tissue transplantation. We hope that this review provides some suggestions for the future design of meniscus repair and regeneration strategies.

The von Hippel-Lindau protein pVHL inhibits ribosome biogenesis and protein synthesis.

pVHL, the product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase complex that targets hypoxia inducible factor α (HIF-α) for ubiquitination and degradation. Besides HIF-α, pVHL also interacts with other proteins and has multiple functions. Here, we report that pVHL inhibits ribosome biogenesis and protein synthesis. We find that pVHL associates with the 40S ribosomal protein S3 (RPS3) but does not target it for destruction. Rather, the pVHL-RPS3 association interferes with the interaction between RPS3 and RPS2. Expression of pVHL also leads to nuclear retention of pre-40S ribosomal subunits, diminishing polysomes and 18S rRNA levels. We also demonstrate that pVHL suppresses both cap-dependent and cap-independent protein synthesis. Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL.

Correction: Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery.

Correction for 'Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery' by Ronggang Liu et al., Food Funct., 2023, 14, 4254-4266, https://doi.org/10.1039/D3FO00092C.

The impact of pre-rehydration guided by carotid corrected flow time on hypotension prevention following general anesthesia induction in patients undergoing gastrointestinal surgery: a prospective randomized controlled trial.

Background: Patients undergoing gastrointestinal surgery often experience hypotension following general anesthesia induction due to insufficient volume. This study aimed to assess whether pre-rehydration guided by carotid corrected flow time (FTc) could mitigate post-induction hypotension induced by general anesthesia. Methods: Patients undergoing resection of gastrointestinal tumors were assigned to either the conventional treatment group (Group C) or the fluid treatment group based on FTc (Group F). Within Group F, patients were further divided into Group A (carotid FTc <340.7 ms) and Group B (carotid FTc ≥340.7 ms) based on pre-rehydration carotid FTc values. Group A patients received pre-rehydration with 250 mL of colloids (hydroxyethyl starch-HES) administered within 15 min until carotid FTc reached ≥340.7 ms to counteract hypovolemia prior to induction. Patients in Group B and Group C received a continuous HES infusion at a rate of 6 mL/kg/h 30 min before induction to compensate for physiological fluid loss. All patients received a perioperative background infusion of 3 mL/kg/h compound sodium chloride, with infusion rates optimized based on mean arterial pressure (MAP) and heart rate (HR). The incidence of post-induction hypotension was compared between Group C and Group F, as well as between Group A and Group B. Results: The incidence of hypotension after induction was significantly lower in Group F compared to Group C (26.4% vs. 46.7%, respectively; p < 0.001). Patients in Group A received significantly more pre-rehydration, leading to a greater increase in carotid FTc values compared to Group B (336.5 ± 64.5 vs. 174.3 ± 34.1 ms, p = 0.002). However, no significant difference in carotid FTc values after pre-rehydration was observed between the groups. There was no significant difference in the incidence of hypotension after general anesthesia induction between Group A and Group B (22.9% vs. 28.8%, p = 0.535). Conclusion: Pre-rehydration based on FTc can effectively reduce the occurrence of post-induction hypotension in patients undergoing gastrointestinal surgery who present with insufficient volume. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=201481.

Value of carotid corrected flow time or changes value of FTc could be more useful in predicting fluid responsiveness in patients undergoing robot-assisted gynecologic surgery: a prospective observational study.

Background: The aim of this study was to evaluate the ability of point-of-care Doppler ultrasound measurements of carotid corrected flow time and its changes induced by volume expansion to predict fluid responsiveness in patients undergoing robot-assisted gynecological surgery. Methods: In this prospective study, carotid corrected flow time was measured using Doppler images of the common carotid artery before and after volume expansion. The stroke volume index at each time point was recorded using noninvasive cardiac output monitoring with MostCare. Of the 52 patients enrolled, 26 responded. Results: The areas under the receiver operating characteristic curves of the carotid corrected flow time and changes in carotid corrected flow time induced by volume expansion were 0.82 and 0.67, respectively. Their optimal cut-off values were 357 and 19.5 ms, respectively. Conclusion: Carotid corrected flow time was superior to changes in carotid corrected flow time induced by volume expansion for predicting fluid responsiveness in this population.

Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery.

Astaxanthin (AXT) is a lipid-soluble carotenoid with good anti-oxidation, hepatic steatosis reduction, anti-inflammation, and intestinal microbiota regulation ability, whose poor stability and pH vulnerability limit its bioavailability. Spirulina protein (SP) derived from spirulina has good emulsifying ability with potential application in nutraceuticals, medicines, and cosmetics. In this study, Pickering emulsions were prepared using a SP-chitosan (CS) complex as an emulsifier. The particle size, zeta potential, and three-phase contact angle of the SP-CS complex with different SP to CS ratios were investigated. A mass ratio of 1 : 2.5 SP-CS complex showed a good emulsifying ability in preparing Pickering emulsion. A higher storage modulus and viscoelasticity were observed with higher SP-CS complex concentrations and oil fractions. The SP-CS Pickering emulsion significantly improved the stability of AXT in different environments. The lipid release rate and AXT bioavailability after digestion of 3 wt% SP-CS complex-stabilized Pickering emulsion reached 70.54 ± 1.59% and 36.60 ± 3.44%, respectively. The results indicated that the SP-CS complex could act as a Pickering emulsion stabilizer and had the potential to deliver protective hydrophobic AXT.

Preparation and evaluation of ovalbumin-fucoidan nanoparticles for nicotinamide mononucleotide encapsulation with enhanced stability and anti-aging activity.

Nicotinamide mononucleotide (NMN) has been recognized as a promising bio-active compound in relieving aging-related mitochondrial dysfunction. Self-assembled nanoparticles were prepared based on interaction between ovalbumin (OVA) and fucoidan to improve the stability and bio-accessibility of NMN. The OVA-fucoidan nanoparticles (OFNPs) displayed outstanding thermal stability and entrapment ability of NMN. The reactive oxygen species (ROS) analysis and senescence-associated ß-galactosidase (SA-ß-gal) staining characterization indicated that NMN encapsulated by OFNPs could effectively alleviate the cellular senescence of d-galactose-induced senescent cells. In vivo Caenorhabitis elegans experiment demonstrated that NMN-loaded OFNPs caused less accumulation of lipofuscin and protected NMN from thermal damage. Compared with free NMN, the NMN-loaded OFNPs prolonged lifespan from 28 to 31 days, increased 26% reproductive ability, and improved 12% body length of Caenorhabitis elegans. The results indicated that the use of nanocarriers could be a good strategy to improve anti-oxidative stress and anti-aging ability of NMN.

Sea bass protein-polyphenol complex stabilized high internal phase of algal oil Pickering emulsions to stabilize astaxanthin for 3D food printing.

The protective effect of sea bass protein (SBP)-(-)-epigallocatechin-3-gallate (EGCG) covalent complex-stabilized high internal phase (algal oil) Pickering emulsions (HIPPEs) on astaxanthin and algal oils was demonstrated in this study. The SBP-EGCG complex with better wettability and antioxidant activity was formed by the free radical-induced reaction to stabilize HIPPEs. Our results show that the SBP-EGCG complex formed dense particle shells surrounding the oil droplets, and the shells were crosslinked with the complex in the continuous phase to produce a network structure. The rheological analysis demonstrated that the SBP-EGCG complex endowed HIPPEs with high viscoelasticity, high thixotropic recovery, and good thermal stability, which were beneficial for three-dimensional (3D) printing applications. HIPPEs stabilized by SBP-EGCG complex were applied to improve the stability and bioaccessibility of astaxanthin and to delay algal oil lipid oxidation. The HIPPEs might become a food-grade 3D printing material served as a delivery system for functional foods.

Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells.

Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.

High internal phase Pickering emulsions stabilized by a cod protein-chitosan nanocomplex for astaxanthin delivery.

High internal phase Pickering emulsions (HIPPEs) stabilized by a food protein have attracted widespread attention. In this study, a novel cod protein-chitosan nanocomplex was prepared through electrostatic interactions and used as a particle emulsifier to stabilize the oil-water interface. The application of the cod protein-chitosan nanocomplex was demonstrated in the formation of stable HIPPEs with an internal phase as high as 84%. The influence of the system composition on the stability, microstructure and rheology of the HIPPEs was determined. The HIPPEs stabilized by the cod protein-chitosan nanocomplex formed a compact three-dimensional network structure, which gave the emulsion a higher storage modulus, viscoelasticity and good thixotropy. Interestingly, the chemical stability of astaxanthin was significantly improved by the developed HIPPEs. The bioavailability of astaxanthin in the HIPPEs stabilized by the nanocomplexes of 2.0% (w/w) cod protein and 0.1% (w/w) chitosan reached 49%. In summary, these results demonstrated that the food-grade cod protein-chitosan nanocomplex had potential in the development of HIPPEs, which could be used as carriers for hydrophobic bioactive compound delivery.

miR-190b promotes colorectal cancer progression through targeting forkhead box protein P2.

microRNA-190b (miR-190b) is abnormally expressed in multiple types of cancer, however, its role in colorectal cancer (CRC) is largely unknown. In the present study, it was demonstrated that miR-190b expression was upregulated in CRC cell lines compared with the normal epithelial colon cell line. Knockdown of miR-190b decreased proliferation, colony formation and invasion, and increased apoptosis of CRC cells. Furthermore, forkhead box protein P2 (FOXP2) was predicted as a target of miR-190b and further validated by luciferase activity reporter assay and western blotting. Rescue experiments showed that knockdown of FOXP2 reversed the inhibitory effects of miR-190b inhibitor on the behavior of the CRC cell lines. Taken together, the present study demonstrated the oncogenic role of miR-190b in CRC through regulation of FOXP2 expression.

Do low-dose corticosteroids improve survival or shock reversal from septic shock in adults? Meta-analysis with trial sequential analysis.

Objective This meta-analysis with trial sequential analysis (TSA) was performed to determine whether low-dose corticosteroids (LDCs) can improve survival or shock reversal from septic shock in adults. Methods A literature search was performed using several databases (Medline, Cochrane Library, Embase, and Chinese Biological Medical Database) until 23 October 2017. The systematic review was registered in PROSPERO. Results Nine randomized controlled trials (RCTs) (n = 1182) were included. LDC intervention improved 7-day shock reversal compared with the control group (relative risk, 1.36; TSA-adjusted 95% confidence interval, 1.20-1.54). LDCs had no statistically significant effects on gastrointestinal bleeding or superinfection. LDCs did not reduce 28-day mortality from septic shock (relative risk, 0.96; TSA-adjusted 95% confidence interval, 0.74-1.24). The TSA indicated that RCTs of about 3000 patients would be needed to draw definitive conclusions; similar results were obtained in a subgroup analysis of nonresponders. Conclusions LDCs improve 7-day shock reversal. However, whether LDCs improve 28-day survival from septic shock in adults remains unclear. The results of well-designed larger RCTs are needed.

Applications of stem cell-derived exosomes in tissue engineering and neurological diseases.

Exosomes are extracellular vesicles with diameters of 30-100 nm that are key for intercellular communication. Almost all types of cell, including dendritic cells, T cells, mast cells, epithelial cells, neuronal cells, adipocytes, mesenchymal stem cells, and platelets, can release exosomes. Exosomes are present in human body fluids, such as urine, amniotic fluid, malignant ascites, synovial fluid, breast milk, cerebrospinal fluid, semen, saliva, and blood. Exosomes have biological functions in immune response, antigen presentation, intercellular communication, and RNA and protein transfer. This review provides a brief overview of the origin, morphological characteristics, enrichment and identification methods, biological functions, and applications in tissue engineering and neurological diseases of exosomes.

[Effects of ganoderma lucidum spores on mitochondrial calcium ion and cytochrome C in epididymal cells of type 2 diabetes rats].

OBJECTIVE: To observe the effects of ganoderma lucidum spores (GLS) on mitochondrial calcium ion and cytochrome C in the epididymal cells of type 2 diabetes rats. METHODS: Fifty adolescent rats were randomly divided into a model group (n=20), a GLS group (n=20) and a control group (n=10). The animals of the former two groups were injected with 2% STZ via vena caudalis for one time to induce type 2 diabetes. Then the model group was given high-fat-sugar diet, the GLS group high-fat-sugar diet + GLS (250 mg/kg x d), and the control group normal diet + CA-citrate sodium buffer. The bilateral epididymides were obtained 10 weeks later and the contents of mitochondrial calcium and cytochrome C detected. RESULTS: Type 2 diabetes models were successfully constructed. The content of mitochondrial calcium in the epididymal cells was significantly higher in the model group ([3.279 +/- 0.502] mg/L) than in the control group ([2.606 +/- 0.048] mg/L, P < 0.01), with no significant difference between the GLS group ([2.693 +/- 0. 196] mg/L) and the control (P > 0.05). In the model group, the content of mitochondrial cytochrome C ([3.213 +/- 1.511] micromol/L) was significantly lower (P < 0.05) while that of cytoplasm cytochrome C ([2.484 +/- 0.661] micromol/L) significantly higher (P < 0.05) than in the control ([5.688 +/- 1.679] micromol/L and [1.574 +/- 0.329] micromol/L, respectively). In the GLS group, the content of mitochondrial cytochrome C ([5.258 +/- 1.560] micromol/L) was higher, with no significant difference (P > 0.05), and that of cytoplasm cytochrome C ([1.727 +/- 0.396] micromol/L) significantly lower than in the model group (P < 0.05), but the difference between the GLS and the control group was not significant (P > 0.05). CONCLUSION: With disequilibrium of calcium homeostasis and damage to mitochondria, there might be excessive apoptosis in the epididymal cells of type 2 diabetes rats. Ganoderma lucidum spores could protect epididymal cells and counteract their apoptosis in diabetic condition.

A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.

FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice. Slug mediated FAM3B-258-induced downregulation of adhesion molecules, upregulation of Cdc42, and invasion of colon cancer cells. The expression of FAM3B-258 in human colorectal adenocarcinomas was positively correlated with Slug. These results suggest that FAM3B-258 promotes colon cancer cell invasion and metastasis through upregulation of Slug.

[Influence of obesity on short-term surgical outcome in patients with gastric cancer].

OBJECTIVE: To explore the influence of obesity on surgical procedure and short-term surgical outcome in patients with gastric carcinoma. METHODS: A total of 426 patients with gastric carcinoma underwent laparotomy in our hospital during January 2006 and June 2008. All the patients were divided into obesity group and non-obesity group according to body mass index (BMI). The thickness of subcutaneous fat (SCF), abdominal anterior-posterior diameter (APD) and transverse diameter (TD) at the umbilicus level were measured by abdominal CT. Furthermore, the surgical data and postoperative conditions including short-term outcome were reviewed and compared between two groups. RESULTS: The incidence of obesity was 29.8% in gastric carcinoma patients. Mean values of SCF thickness, APD and TD in obesity group and non-obesity group were (21.8+/-7.1) mm vs (14.4+/-7.5) mm, (223.2+/-24.6) mm vs (181.8+/-23.5) mm and (323.6+/-23.8) mm vs (285.8+/-24.4) mm (P=0.000). Longer operative time (P=0.007) and less amount of dissected lymph nodes were found in obesity group as compared to non-obesity group (P=0.000). Also, obesity group lasted a longer postoperative period of fever (P=0.000) and experienced more post-operative complications (P=0.005) than non-obesity group did. CONCLUSIONS: Abdominal CT scan may display the abdominal shape of gastric carcinoma patients, hence, it is useful to evaluate the difficulty of surgical procedure. These patients may involve in complicated surgical procedure and worse short-term outcome due to obese abdominal shape. Therefore, perioperative management should be emphasized for these patients.