Ca2+-promoted free radical grafting of whey protein to EGCG: As a novel nanocarrier for the encapsulation of apigenin.

Whey protein (WP) is often used as a delivery carrier due to its superior biological activity and nutritional value. Covalent binding of WP to epigallocatechin gallate (EGCG) can significantly improve the performance of WP in encapsulated materials. Nevertheless, the preparation of WP-EGCG covalent complexes still suffers from low grafting rates. Studies have shown that calcium ions (Ca2+) can modify the structure of proteins. We therefore explored the effect of calcium chloride (CaCl2) on the free radical grafting of EGCG and WP. The experimental results showed that the grafting rate of free radicals increased by 17.89% after adding Ca2+. Furthermore, the impact of WP-EGCG-Ca2+ covalent complex on the entrapment efficiency of apigenin (AP) was further examined, and the results revealed that the entrapment rate could reach 93.66% at an apigenin concentration of 0.2 mg/mL. Simulated gastrointestinal digestion showed that WP-EGCG-Ca2+ covalent complex could significantly improve the bioavailability of AP. The study provides new ideas to broaden the application of WP as a carrier for delivering bioactive substances.

Preclinical Evaluation of JAB-2485, a Potent AURKA Inhibitor with High Selectivity and Favorable Pharmacokinetic Properties.

As a critical mitotic regulator, Aurora kinase A (AURKA) is aberrantly activated in a wide range of cancers. Therapeutic targeting of AUKRA is a promising strategy for the treatment of solid tumors. In this study, we evaluated the preclinical characteristics of JAB-2485, a small-molecule inhibitor of AURKA currently in Phase I/IIa clinical trial in the US (NCT05490472). Biochemical studies demonstrated that JAB-2485 is potent and highly selective on AURKA, with subnanomolar IC50 and around 1500-fold selectivity over AURKB or AURKC. In addition, JAB-2485 exhibited favorable pharmacokinetic properties featured by low clearance and good bioavailability, strong dose-response relationship, as well as low risk for hematotoxicity and off-target liability. As a single agent, JAB-2485 effectively induced G2/M cell cycle arrest and apoptosis and inhibited the proliferation of small cell lung cancer, triple-negative breast cancer, and neuroblastoma cells. Furthermore, JAB-2485 exhibited robust in vivo antitumor activity both as monotherapy and in combination with chemotherapies or the bromodomain inhibitor JAB-8263 in xenograft models of various cancer types. Together, these encouraging preclinical data provide a strong basis for safety and efficacy evaluations of JAB-2485 in the clinical setting.

Magnolol ameliorates fumonisin B1-induced oxidative damage and lipid metabolism dysfunction in astrocyte-like C6 cells.

The neurotoxicity of fumonisin B1 (FB1), a commonly detected mycotoxin in crops and the environment, has attracted considerable attention in recent years. However, no effective method for eliminating FB1 completely exists due to the thermal stability and water solubility of this mycotoxin. Magnolol (MAG) is a neolignane with antioxidative and neuroprotective effects. It has been applied in neurotoxicity treatment. However, the application of MAG to attenuate FB1-induced toxicity has not been reported. This study explored the protective mechanism of MAG against FB1-induced damage in C6 cells through antioxidant and lipid metabolism modulation. Results showed that exposure to 15 µM FB1 caused oxidative stress by changing the levels of malondialdehyde, reactive oxygen species, total superoxide dismutase, catalase, and total glutathione. These changes were reversed by MAG addition, especially at the concentration of 80 µM. The protective effects of MAG were further confirmed by the reduction in the phosphorylation levels of proteins in the MAPK signaling pathway. Lipidomics analysis identified 263 lipids, which belong to 24 lipid classes. Among all of the identified lipids, triglycerides (TGs), diglycerides (DGs), phosphatidylcholines (PCs), wax monoesters (WEs), Cers, and phosphatidylethanolamines (PEs) were major categories. Moreover, nine categories of lipids showed the opposite change trend in the FB1 exposure and MAG 80 groups. A further investigation of the 34 co-occurring differential lipids with remarkable changes (P value < 0.05 and VIP value > 1) in the control, FB1 exposure, and MAG 80 groups was performed. Therein, nine lipids (PCs, LPCs, and SM) were screened out as potential biomarkers to reveal the cytoprotective effects of MAG. This work is the first to investigate the rescue mechanism of MAG in FB1-induced cytotoxicity. The obtained results may expand the application of MAG to alleviate the toxicity of mycotoxins.

A Simulation of the Mechanical Testing of the Cell Membrane and Cytoskeleton.

Cell models play a crucial role in analyzing the mechanical response of cells and quantifying cellular damage incurred during micromanipulation. While traditional models can capture the overall mechanical behavior of cells, they often lack the ability to discern among distinct cellular components. Consequently, by employing dissipative particle dynamics, this study constructed a triangular network-like representation of the cell membrane along with cross-linked cytoskeletal chains. The mechanical properties of both the membrane and cytoskeleton were then analyzed through a series of simulated mechanical tests, validated against real-world experiments. The investigation utilized particle-tracking rheology to monitor changes in the mean square displacements of membrane particles over time, facilitating the analysis of the membrane's storage and loss moduli. Additionally, the cytoskeletal network's storage and loss moduli were examined via a double-plate oscillatory shear experiment. The simulation results revealed that both the membrane and cytoskeleton exhibit viscoelastic behavior, as evidenced by the power-law dependency of their storage and loss moduli on frequency. Furthermore, indentation and microinjection simulations were conducted to examine the overall mechanical properties of cells. In the indentation experiments, an increase in the shear modulus of the membrane's WLCs correlated with a higher Young's modulus for the entire cell. Regarding the microinjection experiment, augmenting the microinjection speed resulted in reduced deformation of the cell at the point of membrane rupture and a lower percentage of high strain.

In silico prediction aided preparation of antioxidant soybean peptides by enzymatic hydrolysis for ameliorating lead exposure-induced toxicity.

Food derived bioactive peptides are prominent dietary supplements to protect against oxidative stress induced by lead (Pb) exposure. This study aimed to develop a new strategy for rapid preparation of highly active antioxidant soybean polypeptides (ASPs) against Pb toxicity. In silico enzymatic hydrolysis simulation and antioxidant activity prediction showed that pepsin, chymotrypsin and bromelain can produce peptides with the highest activity. The preparation process was then optimized, and the obtained ASP showed good antioxidant and metal-chelating activities in vitro. An in vivo study showed that ASP exerted prominent protective effects against Pb-induced cognitive impairment and tissue damage in mice by reducing Pb deposition and enhancing the antioxidant capacity in tissues and was superior to Vc, DMSA or their combination in some aspects. ASP composition analysis demonstrated that its prominent antioxidant activity might be attributed to the high proportion of amino acid residues E, L, P and V in the peptide sequence and L, V and A at the C- and N-termini. In conclusion, in silico prediction could facilitate the preparation of ASP. And the ASP prepared with the new strategy exerted prominent protective effects against Pb toxicity.

Purslane (Portulacae oleracea L.) polysaccharide relieves cadmium-induced colonic impairments by restricting Cd accumulation and inhibiting inflammatory responses.

This study aimed to assess the protective effects of purslane polysaccharide (PP) on colonic impairments in mice exposed to cadmium (Cd). C57BL/6 mice were administered with PP (200-800 mg/kg/day) by gavage for 4 weeks after treatment with 100 mg·L-1 CdCl2. PP significantly reduced Cd accumulation in the colon tissue and promoted the excretion of Cd in the feces. PP could reduce the expression levels of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6) and inhibit the activation of the TLR4/MyD88/NF-κB signaling pathway. In addition, the results of 16S rRNA analysis revealed that PP significantly increased the abundance of probiotics (Lactobacillus), while decreased the abundance of pathogenic bacteria (Lachnospiraceae_NK4A136_group). Following the augmentation of beneficial intestinal bacteria, the treatment with PP led to an increase in the levels of intestinal microbial metabolites, specifically short-chain fatty acids (SCFAs). The SCFAs are known for their anti-inflammatory properties, immune-regulatory effects, and promotion of intestinal barrier function. Additionally, the results suggested that PP effectively impeded the enterohepatic circulation by inhibiting the FXR-FGF15 axis in the intestines of Cd-exposed mice. In summary, PP mitigated the toxic effects of Cd by limiting its accumulation and suppressing inflammatory responses in colon.

Reproductive behavior of fruit flies: courtship, mating, and oviposition.

Many species of the Tephritidae family are invasive and cause huge damage to agriculture and horticulture, owing to their reproductive characteristics. In this review, we have summarized the existing studies on the reproductive behavior of Tephritidae, particularly those regarding the genes and external factors that are associated with courtship, mating, and oviposition. Furthermore, we outline the issues that still need to be addressed in fruit fly reproduction research. The review highlights the implications for understanding the reproductive behavior of fruit flies and discusses methods for their integrated management and biological control. © 2023 Society of Chemical Industry.

Aluminum-maltol induced oxidative stress and reduced AMPK activity via BCK-related energy supply failure in C6 cell.

Aluminum (Al) exposure significantly interferes with the energy supply in astrocytes, which may be a potential mechanism of Al-induced neurotoxicity. This study was designed to explore the mechanisms of Al-induced energy supply impairment in rat C6 astroglioma cell line. Aluminum-maltolate (Al(mal)3) (0.1 mM, 24 h) exposure significantly decreased brain-type creatine kinase (BCK) co-localization with the endoplasmic reticulum (ER) and resulted in mitochondrial dysfunctions, accompanied by a decrease in AMPK phosphorylation. The results of molecular docking showed that Al(mal)3 increased BCK's hydrophobicity and hindered the localization movement of BCK between subcells·H2O2 co-administration was found to exacerbate mitochondrial dysfunction, Ca2+ dyshomeostasis, and apoptosis. After treated with Al(mal)3, additional oxidative stress contributed to BCK activity inhibition but did not promote a further decrease in AMPK phosphorylation. The activation of p-AMPK by its agonist can partially restore mitochondrial function, BCK activity, and ER-localized-BCK levels in Al(mal)3-treated astrocytes. In summary, Al exposure resulted in a sustained depletion of the mitochondrial and antioxidant systems, which was associated with reduced p-AMPK activity and decreased ER-localized-BCK levels in astrocytes. This study provides a theoretical basis for exploring the mechanisms of neurotoxicity induced by Al exposure.

Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Adult patients with tetanus in Anhui Province of China from 2013 to 2022: A retrospective study.

Tetanus is a highly fatal infectious disease with an incubation period of 7 to 8 days. The aim of this study was to identify risk factors for death in tetanus patients, develop a nomogram model for predicting mortality risk. This retrospective study included tetanus patients who were admitted to the intensive care unit department between January 2013 and December 2022. The patients were divided into 2 groups based on their final outcome, namely death group and survival group. Risk factors associated with mortality were analyzed using univariate and multivariate logistic regression analysis. Finally, a nomogram model was developed using the rms package. A total of 91 patients were enrolled in this study, including 54 males and 37 females. The average age of the tetanus patients was 52.88 ±â€…16.56 years, with a mean incubation period of 8.51 ±â€…3.97 days. The foot was the most common injury site (42.86%), and metal product stabbing was the leading cause of injury (48.78%). Ventilator-associated pneumonia was the most frequent complication (21.98%). Univariate and multivariate logistic regression analyses revealed that Ablett classification (odds ratio [OR], 21.999; 95% confidence interval [CI], 4.124-117.352), white blood cell count (OR, 6.033; 95%CI, 1.275-28.552), and autonomic nervous dysfunction (OR, 22.663; 95%CI, 4.363-117.728) as independent risk factors for tetanus patients. The C-index of the nomogram model was 0.942, with an area under the curve of the receiver operating characteristic curve at 0.942 (95%CI, 0.871-0.905). Ablett classification, white blood cell count, autonomic nervous dysfunctions were associated with the prognosis of patients with tetanus. The nomogram model developed based on risk factors has high accuracy.

Discovery of the TLR7/8 Antagonist MHV370 for Treatment of Systemic Autoimmune Diseases.

Toll-like receptor (TLR) 7 and TLR8 are endosomal sensors of the innate immune system that are activated by GU-rich single stranded RNA (ssRNA). Multiple genetic and functional lines of evidence link chronic activation of TLR7/8 to the pathogenesis of systemic autoimmune diseases (sAID) such as Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). This makes targeting TLR7/8-induced inflammation with small-molecule inhibitors an attractive approach for the treatment of patients suffering from systemic autoimmune diseases. Here, we describe how structure-based optimization of compound 2 resulted in the discovery of 34 (MHV370, (S)-N-(4-((5-(1,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide). Its in vivo activity allows for further profiling toward clinical trials in patients with autoimmune disorders, and a Phase 2 proof of concept study of MHV370 has been initiated, testing its safety and efficacy in patients with Sjögren's syndrome and mixed connective tissue disease.

Segmentation of pancreatic tumors based on multi-scale convolution and channel attention mechanism in the encoder-decoder scheme.

BACKGROUND: Computer-aided diagnosis is of great significance to improve the diagnostic accuracy of pancreatic cancer that has an insidious course and does not have obvious symptoms at first. However, segmentation of pancreatic cancer is challenging because the tumors vary in size with the smallest tumor having a size of about 0.5 c m $cm$ in diameter, and most of them have irregular shapes and unclear boundaries. PURPOSE: In this study, we developed a deep learning architecture Multi-Scale Channel Attention Unet (MSCA-Unet) for pancreatic tumor segmentation and collected CT images of 419 patients from The Affiliated Hospital of Qingdao University and a public dataset. We embedded the multi-scale network into the encoder to extract semantic information at different scales and the decoder to provide supplemental information to overcome the loss of information in the upsampling and the drift of the localized tumor due to the upsampling and skip connections. METHODS: We adopted the channel attention unit after the multi-scale convolution to emphasize the informative channels, which was observed to have the effects of accelerating the positioning process, reducing false positives, and improving the accuracy of outlining very small, irregular pancreatic tumors. RESULTS: Our results show that our network outperformed the other current mainstream segmentation networks and achieved a Dice index of 68.03%, a Jaccard of 59.31%, and an FPR of 1.36% on the private dataset Task-01 without data pre-processing. Compared with the other pancreatic tumor segmentation networks on the public dataset Task-02, our network produced the best Dice index, 80.12%, with the assistance of the data pre-processing scheme. CONCLUSIONS: This study strategically utilizes the multi-scale convolution and channel attention mechanism of the architecture to provide a dedicated network for segmentation of small and irregular pancreatic tumors.

Rapid detection of Heterobasidion annosum using a loop-mediated isothermal amplification assay.

Heterobasidion annosum is one of the most aggressive pathogens of Pinus forests in Europe, causing considerable economic losses. To detect H. annosum for disease diagnosis and control, we developed a loop-mediated isothermal amplification (LAMP) reaction with a primer set designed from the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA sequences of H. annosum. In our study, this LAMP assay was found to be capable of efficiently amplifying the target gene within 60 min at 63°C. In specificity tests, H. annosum was positively detected, and other species were negative. The detection limit of this assay was found to be 100 pg·µL-1, and the assay was also successfully tested for use with basidiospore suspensions and wood samples. This study provides a rapid method for diagnosing root and butt rot caused by H. annosum, which will be of use in port surveillance of logs imported from Europe.

Lethal and sublethal effects of broflanilide on four tephritid pests (Diptera: Tephritidae).

BACKGROUND: Fruit flies are internationally important quarantine or invasive pests of many fruits and vegetables and can cause serious economic losses. Long-term reliance on insecticides for controlling these pests has led to increasing resistance to multiple insecticides; hence, a new agent is needed. In this study, the acute toxicity and sublethal effects of the novel insecticide broflanilide on four adult fruit fly species, Bactrocera dorsalis, Bactrocera cucurbitae, Bactrocera tau, and Bactrocera correcta, were evaluated. RESULTS: Broflanilide was effective against B. dorsalis and B. correcta, with lethal concentration values (amount required to kill 50% of animals; LC50 ) of 0.390 and 1.716 mg/L. However, for B. cucurbitae (19.673 mg/L) and B. tau (24.373 mg/L), the LC50 was 50-60 times higher than that of B. dorsalis. The survival rates of B. correcta and B. cucurbitae were significantly lower under LC50 treatment than those of the control (corrected for mortality rate). Sublethal concentrations of broflanilide stimulated fecundity in all species except B. tau. The hatching rate at LC50 was significantly lower for B. correcta and B. tau compared with the control and even more so for B. correcta, which was zero. CONCLUSION: Broflanilide is potentially an effective insecticide for controlling B. dorsalis and B. correcta. However, the variation in toxicity of broflanilide to the four fruit flies suggests that species variation needs to be carefully considered. Our results highlight the importance of clarifying the sublethal effects of insecticides on target insects to ensure the comprehensive evaluation and rational use of insecticides. © 2023 Society of Chemical Industry.

The full model of micropipette aspiration of cells: A mesoscopic simulation.

Studies on the interaction between cells and micromanipulation tools are necessary to optimize the procedures and improve the developmental potential of cells. The molecular dynamics simulation is not possible for such a large-scale simulation, and the spring-damped viscoelastic models and the constitutive equations of the continuum are usually adopted to model the cells as a whole without consideration of the different properties presented by the heterogeneous subcellular components. In this study, we utilized coarse-grained modeling to develop a subcellular model of suspension cell dynamics and a model of a holding micropipette for the fixation of a suspension cell, and designed a large-scale, accurate mesoscopic simulation environment for specific cell micromanipulation. We established a triangular mesh cell membrane and a uniformly distributed, non-intersecting cytoskeleton network and added polymerization/depolymerization processes to connect the cytoskeleton chains with the membrane and cross-linking proteins. In the cell aspiration model, we adopted the profile of the reversed Poiseuille flow to calibrate the viscosity of the fluid and set the bounce-back condition and the appropriate solid-fluid force coefficient to realize non-slip flow at the boundary. The rheological properties of the cells during micropipette aspiration were further analyzed in the simulation by varying parameters such as the inner diameter of the micropipette, negative pressure, and maximum bond length. The model well reproduced the experimentally observed cell deformation phenomenon at low and high pressures. The dynamic response of the cell elongation observed from the simulation was consistent with that obtained from the analysis of the experimental data collected from a custom-designed micromanipulation system. STATEMENT OF SIGNIFICANCE: In this study, we extended the coarse-grained modeling of cells by developing a relatively large-scale micromanipulation environment consisting of a subcellular cell dynamics model and a fluid flow model for cell aspiration. We simulated cytoskeleton filaments that were uniformly distributed in space via applying Harmonic energy to model cytoskeleton with a high level of fidelity. The shortcoming of the soft repulsion in the solid-fluid interaction in the current simulation technique was solved by implementing the bounce-back boundary and the condition that the total force imposed by the wall particles on the fluid particles was equal to the pressure of the fluid. This work paved the way for understanding the mechanical properties of cells and improving the biological efficacy of micromanipulation.

Comparative study of aluminum speciation on brain-type creatine kinase: Enzyme kinetic, molecular docking, cellular experiment, and mouse model study.

Brain-type Creatine kinase (CK-BB), which has a high affinity for Aluminum (Al), and its abnormality is closely related to neurodegenerative diseases. In this study, the comparative effect of Al speciation on the bioactivity of CK-BB has been studied by the inhibition kinetics method, molecular docking, cellular experiment, and mouse model study. Results showed that the half-inhibitory concentration of AlCl3 was 0.67 mM, while Al(mal)3 was 3.81 mM. Fluorescence spectra showed that Al(mal)3 had a more substantial effect on the endogenous fluorescence of CK-BB than AlCl3. Molecular docking showed that AlCl3 was closer to the active site of CK-BB. C6 cells were used to explore the enzyme activity and intracellular distribution of CK-BB by AlCl3 or Al(mal)3. AlCl3 treatment may directly affect CK-BB activity and cause insufficient local ATP supply in cells which affected the formation of F-actin and cell morphology. The change in the hydrophobicity of CK-BB induced by Al(mal)3 affected the movement of CK-BB, which subsequently activated thecytochrome C (Cyt C)/Caspase 9/Caspase 3 pathway. Similar results have been found in vivo experiments. This study demonstrated that interaction between Al and CK-BB might be related to the process of Al-induced energy metabolism disorders, in which the Al speciation revealed differentiated toxicity mechanisms.

Mechanical Characterization and Modelling of Subcellular Components of Oocytes.

The early steps of embryogenesis are controlled exclusively by the quality of oocyte that linked closely to its mechanical properties. The mechanical properties of an oocyte were commonly characterized by assuming it was homogeneous such that the result deviated significantly from the true fact that it was composed of subcellular components. In this work, we accessed and characterized the subcellular components of the oocytes and developed a layered high-fidelity finite element model for describing the viscoelastic responses of an oocyte under loading. The zona pellucida (ZP) and cytoplasm were isolated from an oocyte using an in-house robotic micromanipulation platform and placed on AFM to separately characterizing their mechanical profiling by analyzing the creep behavior with the force clamping technique. The spring and damping parameters of a Kelvin-Voigt model were derived by fitting the creeping curve to the model, which were used to define the shear relaxation modulus and relaxation time of ZP or cytoplasm in the ZP and cytoplasm model. In the micropipette aspiration experiment, the model was accurate sufficiently to deliver the time-varying aspiration depth of the oocytes under the step negative pressure of a micropipette. In the micropipette microinjection experiment, the model accurately described the intracellular strain introduced by the penetration. The developed oocyte FEM model has implications for further investigating the viscoelastic responses of the oocytes under different loading settings.

Rice hull insoluble dietary fiber alleviated experimental colitis induced by low dose of dextran sulfate sodium in cadmium-exposed mice.

Cadmium (Cd), an important toxic environmental pollutant, can invade the gastrointestinal tract and induce the occurrence of gastrointestinal diseases. This study aimed to investigate the protective effect of rice hull insoluble dietary fiber (RHF) on Cd-promoted colitis induced by low dose of dextran sulfate sodium. Administration of RHF attenuated inflammation by limiting Cd accumulation and regulating intestinal immune homeostasis in colitis mice with Cd exposure. RHF could maintain the structure of the gut barrier by increasing mucin secretion and intestinal tight connectivity in mice. Subsequently, RHF repressed the colonic inflammation mediated by the TLR4/MyD88/NF-κB pathway, and inhibited the transcription regulation of inflammatory cytokines. Furthermore, RHF showed an enhancement of a variety of probiotics, such as Eubacterium and Faecalibaculum. RHF also inhibited the growth of pathogenic bacteria, including Erysipelatoclostridium, Helicobacter and Bacteroides. The growth of beneficial bacteria was also accompanied by reversing the decline in short-chain fatty acids, supporting the initial potentiality of RHF as a prebiotic in cases of damage by Cd exposure in colitis mice. Importantly, RHF also remained resistant to Cd toxicity in colitis mice when the gut microbiota was depleted by antibiotics. We suggest that RHF could be used as a novel dietary supplement strategy against Cd-exacerbated colitis.

Comparative study of aluminum (Al) speciation on apoptosis-promoting process in PC12 cells: Correlations between morphological characteristics and mitochondrial kinetic disorder.

Aluminum contamination in environment is very serious and the central nervous system is the main target of aluminum toxicity. The neurotoxic of aluminum is closely related to its speciation. PC12 cells were taken as the cell model to compare the morphological characteristics and mitochondrial kinetic disorder of two speciation of aluminum compounds (AlCl3 and aluminum-maltolate (Al(mal)3)). When the concentration of AlCl3 was 3 mM, the intracellular aluminum ion content was 3.87 times that of the 0.5 mM Al(mal)3 treatment group. At the 3 mM AlCl3 treatment group, intracellular ion homeostasis was disrupted. Abnormally elevated Ca2+ levels inhibited protein kinase B (AKT) phosphorylation, resulting in impaired cell morphology. At the 0.5 mM Al(mal)3 treatment group, abnormally high levels of Ca2+ caused mitochondrial kinetic disorder, which led to impaired cellular energy metabolism. Al(mal)3 had shown more cytotoxic in PC12 than AlCl3 at the same concentration. AlCl3 tended to inhibit the phosphorylation of AKT and damages cell morphology. Al(mal)3 mainly affected mitochondrial kinetic disorder, which led to impaired cellular energy metabolism. These findings provided experimental evidence for in-depth research on aluminum-induced neurotoxicity.

Low Serum Superoxide Dismutase Is Associated With a High Risk of Cognitive Impairment After Mild Acute Ischemic Stroke.

Background: Post-stroke cognitive impairment (PSCI) is a common complication after stroke, but effective therapy is limited. Identifying potential risk factors for effective intervention is warranted. We investigated whether serum superoxide dismutase (SOD) levels were related to cognitive impairment after mild acute ischemic stroke (AIS) by using a prospective cohort design. Methods: A total of 187 patients diagnosed with mild AIS (National Institutes of Health Stroke Scale ≤ 8) were recruited. Serum SOD, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured, and cognitive assessments (Mini-Mental State Examination, MMSE; Montreal Cognitive Assessment, MoCA) were performed in the early phase (within 2 weeks). These indexes and assessments were repeated at 3 months after onset. MoCA < 22 was defined as early cognitive impairment (CI-E) within 2 weeks and late cognitive impairment (CI-L) at 3 months after stroke. Results: In a survey, 105 of 187 (56.1%) patients were identified as CI-E after mild AIS. Lower serum SOD associated with higher inflammatory biomarkers (ESR, CRP, and IL-6) and worse cognitive scores was observed in CI-E patients. In a survey, 39 of 103 (37.9%) stroke patients who completed the 3-month follow-up were identified as CI-L. Serum SOD was consistently lower in CI-L patients at baseline and 3 months and positively associated with cognitive scores. In adjusted analyses, low serum SOD at baseline was independently associated with high risks of CI-E and CI-L, with odds ratios (ORs) of 0.64 and 0.33 per standard deviation increase in serum SOD, respectively. Multiple-adjusted spline regression models showed linear associations between serum SOD and CI-E (P = 0.044 for linearity) and CI-L (P = 0.006 for linearity). Moreover, 35.2% (19/54) of CI-E patients cognitively recovered during the 3-month follow-up. In multivariable analysis, SOD was identified as a protective factor for cognitive recovery after stroke (OR 1.04, 95% CI: 1.01-1.08, P = 0.024). Conclusion: We demonstrate that low serum SOD is associated with a high risk of cognitive impairment after mild AIS, indicating SOD may be a potential modifiable factor for PSCI.