Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

N-octylpyridine hydrogen sulphate ionic liquid for multifunctional fluorescent response in different solvents.

Ionic liquids (ILs) have attracted considerable interest in the last two decades owing to their unique fluorescent properties. Herein, N-octylpyridine hydrogen sulphate ([OP]HSO4) was synthesised and characterised using 1H NMR and infrared spectroscopies. In addition, the fluorescence spectra of [OP]HSO4 in water, methanol, ethanol and acetonitrile were studied. In a single solvent, as the concentration of the solvent (methanol, ethanol or acetonitrile) increases, the fluorescence intensity of the IL first increases and then decreases. A similar trend was observed in their mixed solvents with water. Moreover, the fluorescence intensity of [OP]HSO4 decreases with increasing temperature. A fluorescence intensity reduction of only 4.46% for [OP]HSO4 after continuous scanning for 40 cycles under the maximum excitation state was analysed. The lack of photobleaching observed in [OP]HSO4 indicates its good photobleaching resistance.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.

Hierarchical Composite Scaffold with Deferoxamine Delivery System to Promote Bone Regeneration via Optimizing Angiogenesis.

A bone defect refers to the loss of bone tissue caused by trauma or lesions. Bone defects result in high morbidity and deformity rates worldwide. Autologous bone grafting has been widely applied in clinics as the gold standard of treatment; however, it has limitations. Hence, bone tissue engineering (BTE) has been proposed and developed as a novel therapeutic strategy for treating bone defects. Rapid and effective vascularization is essential for bone regeneration. In this study, a hierarchical composite scaffold with deferoxamine (DFO) delivery system, DFO@GMs-pDA/PCL-HNTs (DGPN), was developed, focusing on vascularized bone regeneration. The hierarchical structure of DGPN imitates the microstructure of natural bone and interacts with the local extracellular matrix (ECM), facilitating cell adhesion and proliferation. The addition of 1 wt% of halloysite nanotubes (HNTs) improved the material properties. Hydrophilic and functional groups conferred by polydopamine (pDA) modifications strengthened the scaffold bioactivity. Gelatin microspheres (GMs) protected the pharmacological activity of DFO, achieving local application and sustained release for seven days. DFO effectively promoted angiogenesis by activating the signaling pathway of hypoxia inducible factor-1 α (HIF-1 α). In addition, DFO synergized with HNTs to promote osteogenic differentiation and matrix mineralization. These results indicated that DGPN promoted bone regeneration and accelerated cranial defect healing. This article is protected by copyright. All rights reserved.

Polymerized PEI-modified lignin polyphenolic materials by acid hydrolysis-phase separation for removal of Cr (VI) from industrial wastewater.

Cr (VI) accumulates in an aqueous environment and exhibits huge harm to human health and the ecological system. Developed lignin biomass materials are complicated to prepare and have limited properties, and advances in lignin phenolic modification are lacking. Herein, an aminated poplar lignin-pyrogallol (PLP-PEI) with a simple design and adjustable phenolic hydroxyl content was developed using the acid hydrolysis-phase separation (AH-PS) method, and modified by the atom transfer radical polymerization (ATRP) strategy. Through diverse characterization analysis, the structural changes of PLP-PEI in the step-by-step synthesis process were monitored. An effective biomass capture system (Bio-Cap) was shown via systematically investigating the adsorption behaviors of Cr (VI) on PLP-PEI under various environmental conditions. Benefiting from introducing phenolic hydroxyl and amino groups, PLP-PEI demonstrated efficient adsorption capacity (598.80 mg/g for Cr (VI)). Additionally, the material also exhibited advantages, including monomeric chemisorption properties, strong reduction capability, and stable regeneration properties. Multiple driving forces were involved in the capture and removal process of Cr (VI), including complexation and electrostatic interaction. The low-cost natural biomass resources supported the industrial-scale synthesis and practical application of advanced aminated lignin polyphenol material, which showed outstanding advantages and enormous potential in the field of water environmental restoration.

First report of four rare strongylid species infecting endangered Przewalski's horses (Equus ferus przewalskii) in Xinjiang, China.

BACKGROUND: The Przewalski's horse (Equus ferus przewalskii) is the only surviving wild horse species in the world. A significant population of Przewalski's horses resides in Xinjiang, China. Parasitosis poses a considerable threat to the conservation of this endangered species. Yet, there is limited information on the nematode parasites that infect these species. To deepen our understanding of parasitic fauna affecting wild horses, we identified the intestinal nematodes of Przewalski's horses in Xinjiang and added new barcode sequences to a public database. METHODS: Between 2018 and 2021, nematodes were collected from 104 dewormed Przewalski's horses in Xinjiang. Each nematode was morphologically identified to the species level, and selected species underwent DNA extraction. The extracted DNA was used for molecular identification through the internal transcribed spacer 2 (ITS2) genetic marker. RESULTS: A total of 3758 strongylids were identified. To the best of our knowledge, this is the first study to identify four specific parasitic nematodes (Oesophagodontus robustus, Bidentostomum ivashkini, Skrjabinodentus caragandicus, Petrovinema skrjabini) and to obtain the ITS2 genetic marker for P. skrjabini. CONCLUSIONS: The ITS2 genetic marker for P. skrjabini enriches our understanding of the genetic characteristics of this species and expands the body of knowledge on parasitic nematodes. Our findings extend the known host range of four strongylid species, thereby improving our understanding of the relationship between Przewalski's horses and strongylids. This, in turn, aids in the enhanced conservation of this endangered species. This study introduces new instances of parasitic infections in wild animals and offers the DNA sequence of P. skrjabini as a valuable resource for molecular techniques in nematode diagnosis among wildlife.

All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity.

Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro-inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro-inflammatory M1 to anti-inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all-natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen-based all-natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.

Organic substitution stimulates ammonia oxidation-driven N2O emissions by distinctively enriching keystone species of ammonia-oxidizing archaea and bacteria in tropical arable soils.

Partial organic substitution (POS) is pivotal in enhancing soil productivity and changing nitrous oxide (N2O) emissions by profoundly altering soil nitrogen (N) cycling, where ammonia oxidation is a fundamental core process. However, the regulatory mechanisms of N2O production by ammonia oxidizers at the microbial community level under POS regimes remain unclear. This study explored soil ammonia oxidation and related N2O production, further building an understanding of the correlations between ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) activity and community structure in tropical arable soils under four-year field management regimes (CK, without fertilizer N; N, with only inorganic N; M1N1, with 1/2 organic N + 1/2 inorganic N; M1N2, with 1/3 organic N + 2/3 inorganic N). AOA contributed more to potential ammonia oxidation (PAO) than AOB across all treatments. In comparison with CK, N treatment had no obvious effects on PAO and lowered related N2O emissions by decreasing soil pH and downregulating the abundance of AOA- and AOB-amoA. POS regimes significantly enhanced PAO and N2O emissions relative to N treatment by promoting the abundances and contributions of AOA and AOB. The stimulated AOA-dominated N2O production under M1N1 was correlated with promoted development of Nitrososphaera. By contrast, the increased AOB-dominated N2O production under M1N2 was linked to the enhanced development of Nitrosospira multiformis. Our study suggests organic substitutions with different proportions of inorganic and organic N distinctively regulate the development of specific species of ammonia oxidizers to increase associated N2O emissions. Accordingly, appropriate options should be adopted to reduce environmental risks under POS regimes in tropical croplands.

Well-controlled gestational diabetes mellitus without pharmacologic therapy decelerates weight gain in infancy.

Aim: There are no prospective longitudinal studies on the association between well-controlled gestational diabetes mellitus (GDM) without pharmacologic therapy and the physical growth of offspring in infancy. We aimed to identify the trajectories in physical growth (from 0-12 months of age) in the offspring of mothers with well-controlled GDM without pharmacologic therapy in a prospective cohort in China. Methods: This study included 236 offspring of mothers with GDM and 369 offspring of mothers without GDM. Mothers with GDM were not on pharmacologic therapy. The length and weight of infants were measured at 0, 1, 3, 6, and 12 months. Linear mixed-effect models and linear mixed-effect models were applied. Results: The fully adjusted model showed that the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and BMI-for-age z-score (BMIZ) were similar at birth for the GDM and control groups. However, subsequent increases in WAZ and BMIZ for the GDM group lagged the increases for the control group at the subsequent periods of observation, 0-1, 0-6, and 0-12 months. Conclusions: Well-controlled GDM without pharmacologic therapy may normalize physical growth of offspring at birth and decelerate their weight gain in infancy. Whether glycemic control can mitigate the long-term effects of GDM on the growth trajectory in offspring remains unclear.

First record of traumatic myiasis obtained from forest musk deer (Moschus berezovskii).

Myiasis is an infestation of maggots on living tissue in humans and animals all over the world. It is known to occur in wild animals, while no information is reported in forest musk deer (Moschus berezovskii). During our research on the conservation of forest musk deer, we found a new record of traumatic myiasis of an injured forest musk deer. The flies are likely Lucilia caesar (Linnaeus, 1758) according to the results of DNA barcoding technology. We report traumatic myiasis of forest musk deer for the first time, which expands the information on parasite and myiasis of forest musk deer and confirms the potential risk of traumatic myiasis of forest musk deer.

Modulating the Acidic and Basic Site Concentration of Metal-Organic Framework Derivatives to Promote the Carbon Dioxide Epoxidation Reaction.

Metal-organic framework (MOF) is an ideal precursor/template for porous carbon, and its active components are uniformly doped, which can be used in energy storage and catalytic conversion fields. Metal-organic framework PCN-224 with carboxylporphyrin as the ligand was synthesized, and then Zn2+ and Co2+ ions were coordinated in the center of the porphyrin ring by post-modification. Here, PCN-224-ZnCo with different ratios of bimetallic Zn2+ /Co2+ ions were used as the precursor, and the metal-nitrogen-carbon(M-N-C) material of PCN-224-ZnCo-950 was obtained by pyrolyzing the precursor at 950 °C in Ar. Because Zn is easy to volatilize at 950 °C, the formed M-N-C materials can reflect different Co contents and different basic site concentrations. The formed material still maintains the original basic framework. With the increase of Zn2+ /Co2+ ratio in precursor, the concentration of N-containing alkaline sites in pyrolysis products gradually increase. Compared with the precursor, PCN-224-ZnCo1 -950 with Zn2+ /Co2+ =1 : 1 has greatly improved basicity and suitable acidic/ alkaline site concentration. It can be efficiently used to carbon dioxide absorption and catalyze the cycloaddition of CO2 with epoxide. More importantly, the current method of adjusting the acidic/basic sites in M-N-C materials through volatilization of volatile metals can provide an effective strategy for adjusting the catalysis of MOF derivatives with porphyrin structure.

Evaluation of isolated abdominal visceral artery dissection with multi-scale spiral computed tomography: a retrospective case series.

BACKGROUND: To evaluate the role of multi-slice spiral computed tomography (MSCT) angiography in the diagnosis of spontaneous isolated visceral artery dissection (SIVAD). METHODS: Twenty-seven patients with abdominal SIVAD were included in the study. The MSCT scans of the patients were subjected to various post-processing techniques to visualize the visceral artery wall. Clinical features including arterial dissection, thrombosis, dissection length, true/false lumen, and complications were recorded. RESULTS: Type I, IIa, and IIb SIVADs were observed in 11, 6, and 10 patients, respectively. Superior mesenteric artery (SMA) dissection was the most common (n = 16), followed by abdominal aortic dissection (n = 6), splenic artery dissection (n = 2), renal artery dissection (n = 2), and splenic artery dissection (n = 1). One patient with SMA dissection suffered small intestine ischemia, 1 with splenic artery dissection had splenic infarction, and 1 patient with left renal artery dissection experienced renal infarction. The false lumen was bigger than the true lumen in 20 patients, with 9 patients having thrombus. The true lumen was bigger than the false lumen in 7 patients. CONCLUSIONS: MSCT angiography is a valuable technique in the diagnosis and treatment of patients with SIVAD. Patients with abdominal pain suspected due to SIVAD should be examined with MSCT angiography for early detection of SIVAD.

Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14.

Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo. Exposure to LPS (1 µg/mL) induced inflammatory responses in RAW264.7 cells, evidenced by marked increases in the expression of MHC II molecules and the secretion of NO and IL-6, and by activation of MyD88/NF-κB p65 signaling pathway, as well as the expression of CD14 and TLR4. These changes were dose-dependently attenuated by pretreatment baicalin (12.5-50 µM), but not by baicalin post-treatment. In RAW264.7 cells without LPS stimulation, baicalin dose-dependently inhibit the protein and mRNA expression of CD14, but not TLR4. In RAW264.7 cells with CD14 knockdown, baicalin pretreatment did not prevent inflammatory responses and activation of MyD88/NF-κB p65 pathway induced by high concentrations (1000 µg/mL) of LPS. Furthermore, baicalin pretreatment also inhibited the expression of CD14 and activation of MyD88/NF-κB p65 pathway in LPS-induced hepatocyte-derived HepG2 cells and intestinal epithelial-derived HT-29 cells. In mice with intraperitoneal injection of LPS and in DSS-induced UC mice, oral administration of baicalin exerted protective effects by inhibition of CD14 expression and inflammation. Taken together, we demonstrate that baicalin pretreatment prevents LPS-induced inflammation in RAW264.7 cells in CD14-dependent manner. This study supports the therapeutic use of baicalin in preventing the progression of LPS-induced inflammatory diseases.

A wide-frequency range dielectric tuning of BaTiO3 by embedding metal nanocrystals.

Fe nanocrystals (NCs) were embedded into the epitaxial BaTiO3 (BTO) matrix. According to optimized growth processes, a novel nanocomposite system was constructed, which consisted a well epitaxial BTO layer and three-dimensional Fe NCs. Based on this, the different dielectric response in the regions of low temperature-high frequency and low frequency-high temperature were revealed by the contribution of hopping and interfacial polarizations, respectively. With the increased amount of Fe NCs, the obvious enhancement in the low-frequency conductivity, middle frequency capacitance, and high-frequency inductive effect was found. The embedded metal NCs play an important role in tuning the dielectric behaviors and AC conductivity of oxide dielectrics. This significant rectification effect in wide-frequency ranges opens up a new direction for designing embedded nano-capacitors.

Associations between gestational diabetes mellitus and the neurodevelopment of offspring from 1 month to 72 months: study protocol for a cohort study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common gestational disease and an important global public health problem. GDM may affect the short-term and long-term health of offspring, but the associations between GDM and the neurodevelopment of offspring of mothers with GDM (OGDM) are still unclear, and studies based on the Chinese population are lacking. We aim to determine the associations between GDM and the neurodevelopment of OGDM by studying a cohort of OGDM and offspring of non-GDM mothers. METHODS AND ANALYSIS: The single-centre prospective cohort study is being conducted in China over 7 years. A total of 490 OGDM (GDM group) and 490 fromof healthy mothers (control group) will be enrolled during the same period. Baseline characteristics, neuropsychological development scores and clinical data at specific time points (at 0, 1, 3, 6, 12, 24, 36, 48, 60 and 72 months old) will be collected from the children in both groups until the age of 6 years. The associations between GDM and the neurodevelopment of OGDM from infancy to preschool age will be analysed using a multiple linear regression model adjusted for confounders. In addition, we will compare longitudinal data to further assess the effects of GDM on neurodevelopmental trajectories. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Children's Hospital of Chongqing Medical University (Approval Number: (2019) Institutional Review Board (IRB) (STUDY) No. 85). The findings of this study will be disseminated through open access journals, peer-reviewed journals and scientific meetings. TRIAL REGISTRATION NUMBER: NCT03997396.

[Calculation of water equivalent diameter based on anteroposterior localizer CT images].

ObjectiveTo explore a method for calculating water equivalent diameter (Dw) based on localizer CT images for calculation of the size specific dose estimates (SSDE).MethodGE Revolution CT and LightSpeed VCT were used to scan CT dose index phantoms 16 cm and 32 cm in diameter at the tube voltages of 80, 100 and 120 kV to obtain the axial image and anteroposterior localizer radiograph. According to the definition of CT Hounsfield unit, the axial images were used to calculate the conversion factors that convert the phantom thickness to water equivalent thickness. The gray value of the localizer radiograph and the water equivalent thickness were calibrated with a linear equation, and the parameters of the calibration were used to calculate the water equivalent thickness. The method was verified using 2 CT dose index phantoms and in 22 patients undergoing chest and abdominal CT examination.ResultComparison of the water equivalent diameter (Dw) based on the localizer radiograph and axial image of the 2 phantoms showed that the percentage difference between Dw from the axial images and from the localizer radiograph was below 3%. The trend of Dw variations with location in the two methods was sonsistent. The difference in Dw in intermediate region of interest between the axial image and the localizer radiograph from the 22 patients was below 6.6%. With the mean Dw in the ROI, the maximum percentage difference was 7.5%.ConclusionCalibration of the gray value of the localizer radiograph and the water equivalent thickness using the axial image and localizer radiograph of CT dose index phantoms allows quick calculation of the SSDE based on the parameters of calibration.

Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway.

BACKGROUND: Intestinal epithelial barrier dysfunction, which involves myosin light chain kinase (MLCK) activation, contributes to the occurrence and progression of inflammation in inflammatory bowel disease (IBD). Wogonoside helps maintain intestinal homeostasis in mice with dextran sulfate sodium (DSS)-induced colitis, but it is unclear whether it modulates intestinal barrier function. PURPOSE: Here, we demonstrate that wogonoside protects against intestinal barrier dysfunction in colitis via the MLCK/pMLC2 pathway both in vivo and in vitro. METHODS: Caco-2 cell monolayers treated with the proinflammatory cytokine TNF-α showed barrier dysfunction and were assessed in the absence and presence of wogonoside for various physiological, morphological, and biochemical parameters. Colitis was induced by 3% DSS in mice, which were used as an animal model to explore the pharmacodynamics of wogonoside. We detected MLCK/pMLC2 pathway proteins via western blot analysis, assessed the cytokines IL-13 and IFN-γ via ELISA, tested bacterial translocation via fluorescence in situ hybridization (FISH) and a proper sampling of secondary lymphoid organs for bacterial culture. In addition, the docking affinity of wogonoside and MLCK was observed with DS2.5 software. RESULTS: Wogonoside alleviated the disruption of transepithelial electrical resistance (TER) in TNF-α exposured Caco-2 cell; FITC-dextran hyperpermeability; loss of the tight junction (TJ) proteins occludin, ZO-1 and claudin-1 in Caco-2 cell monolayers; and bacterial translocation in colitic mice. Moreover, wogonoside reduced the levels of the proinflammatory cytokines IL-13 and IFN-γ to maintain intestinal immune homeostasis. Transmission electron microscopy (TEM) confirmed that wogonoside ameliorated the destruction of intestinal epithelial TJs. Wogonoside not only inhibited the cytoskeletal F-actin rearrangement induced by TNF-α, stabilized the cytoskeletal structure, suppressed MLCK protein expression, and reduced MLC2 phosphorylation. In addition, the results of molecular docking analysis showed that wogonoside had a high affinity for MLCK and formed hydrogen bonds with the amino acid residue LYS261 and π bonds with LYS229. CONCLUSION: Collectively, our study indicates that wogonoside alleviates colitis by protecting against intestinal barrier dysfunction, and the potential mechanism may involve regulation of TJs via the MLCK/pMLC2 signaling pathway. Meanwhile, our study also explains the success of S. baicalensis in the treatment of ulcerative colitis (UC).

Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway.

Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg-1 ·d-1, i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1ß and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5-50 µM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC.

Polysaccharide from Radix Codonopsis has beneficial effects on the maintenance of T-cell balance in mice.

Immunity due to immune balance contributes to disease prevention and treatment. Radix Codonopsis polysaccharide (RCP) is isolated from the root of the Chinese herb Codonopsis pilosula. Previous studies have indicated that RCP has immunomodulatory activities; however, the effects of RCP on immunity, especially immune balance, are still largely unknown. In the present study, we investigated the effects of RCP on T-cell balance in mice. The mice were pretreated intragastrically with or without RCP for 15 days and injected with hydrocortisone on days 10-15 to disturb the immune system. The spleen and thymus were weighed and used to calculate immune organ indexes. The percentages of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, regulatory T cells (Tregs) and Th17 cells in peripheral blood were assayed by flow cytometry. Pro-inflammatory and anti-inflammatory cytokines, TNF-α, IL-1ß and IL-10, in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that RCP pretreatment could maintain the homeostasis of CD8+ T cells, Tregs, Th17 cells, TNF-α, IL-1ß and IL-10 in hydrocortisone-treated mice. Furthermore, RCP pretreatment maintained the immune balance of CD4+/CD8+ T cells, Th1/Th2 cells, Tregs/Th17 cells, IL-10/TNF-α and IL-10/IL-1ß. Taken together, RCP pretreatment had beneficial effects on the maintenance of T-cell balance against hydrocortisone disturbance in mice and potential to be developed into novel functional food.

Long non-coding RNA MALAT1 regulates BLCAP mRNA expression through binding to miR-339-5p and promotes poor prognosis in breast cancer.

The human genome transcribes a large amount of non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs. LncRNAs and microRNAs have been shown to play a critical regulatory role in tumorigenesis and progression. Competitive endogenous RNAs (ceRNAs) affect other RNAs transcription through competitively binding to common microRNAs (miRNAs). MALAT1 is a typical lncRNA that is markedly up-regulated in breast cancer. However, current understanding of the involvement of MALAT1 in breast cancer development and prognosis remains unclear. In the present study, the expression of MALAT1 in clinical samples of breast cancer tissues was found to be significantly up-regulated that was consistent with the result based on the dataset of the Cancer Genome Atlas (TCGA) at cBioportal. A negative correlation between overall survival and the expression of MALAT1 was statistically significant in the group of diagnosis age below 60 or in the group of infiltrating ductal carcinoma analyzed by TCGA database, which declared that MALAT1 might be a potentially useful prognostic factor. Furthermore, the combination of bioinformatics prediction with experimental verifications indicated that lncRNA MALAT1 can regulate BLCAP mRNA expression through binding to miR-339-5p.