Polydopamine-Based Resveratrol-Hyaluronidase Nanomedicine Inhibited Pancreatic Cancer Cell Invasive Phenotype in Hyaluronic Acid Enrichment Tumor Sphere Model.

The dense storm microenvironment formed by an excessively cross-linked extracellular matrix, such as hyaluronic acid and collagens, serves as a major barrier that prevents drugs from reaching the deeper tumor. Current traditional two-dimensional (2D) cultures are not capable of modeling this drug delivery barrier in vitro. Thus, tumor spheroids have become increasingly important in cancer research due to their three-dimensional structure. Currently, various methods have been developed to construct tumor spheroids. However, there are still challenges, such as lengthy construction time, complex composition of added growth factors, and high cultivation costs. To address this technical bottleneck, our study combined the GelMA hydrogel system to develop a rapid and high-yield method for tumor spheroids generation. Additionally, we proposed an evaluation scheme to assess the effects of drugs on tumor spheroids. Building on the hyaluronic acid-rich pathological tumor microenvironment, we constructed a resveratrol-loaded nano-drug delivery system with tumor stroma modulation capability and used a three-dimensional (3D) tumor sphere model to simulate in vivo tumor conditions. This process was utilized to completely evaluate the ability of the nano-drug delivery system to enhance the deep penetration of resveratrol in the tumor microenvironment, providing new insights into future oncology drug screening, efficacy assessment, and drug delivery methods.

Sodium butyrate administration improves intestinal development of suckling lambs.

This study was conducted to investigate the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. Forty lambs of 7 d old, with an average body weight (BW) of 4.46 ±â€…0.45 kg, were allocated into the control (CON) or SB group, with each group having five replicate pens (n = 5). Lambs were orally administered SB at 1.8 mL/kg BW in the SB group or the same volume of saline in the CON group. Treatments were administered from 7 to 35 d of age, when one lamb from each replicate was slaughtered to obtain intestinal tissues and contents. The results showed that supplementation with SB tended to increase the BW (P = 0.079) and the starter intake (P = 0.089) of lambs at 35 d of age. The average daily gain of lambs in the SB group was significantly greater than that in the CON group (P < 0.05). The villus height of jejunum in the SB group was markedly higher (P < 0.05) than that in the CON group. In ileum, lambs in the SB group had lower (P < 0.05) crypt depth and greater (P < 0.05) villus-to-crypt ratio than those in the CON group. Compared with the CON group, the mRNA and protein expressions of Claudin-1 and Occludin were increased (P < 0.05) in the SB group. Supplementation with SB decreased the relative abundances of pathogenic bacteria, including Clostridia_UCG-014 (P = 0.094) and Romboutsia (P < 0.05), which were negatively associated with the intestinal barrier function genes (P < 0.05). The relative abundance of Succiniclasticum (P < 0.05) was higher in the SB group, and it was positively correlated with the ratio of villi height to crypt depth in the jejunum (P < 0.05). Compared with the CON group, the function "Metabolism of Cofactors and Vitamins" was increased in the SB group lambs (P < 0.05). In conclusion, SB orally administration during suckling period could improve the small intestine development and growth performance of lambs by inhibiting the harmful bacteria (Clostridia_UCG-014, Romboutsia) colonization, and enhancing intestinal barrier functions.

It is well known that butyrate and its derivatives have various benefits for the rumen development of ruminants, whereas its effects on the small intestine in preweaned lambs have received little attention. Therefore, the present study investigated the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. The results indicated that SB dietary treatment has beneficial effects on the small intestine development and growth performance of suckling lambs.

Influence of probiotic supplementation on the growth performance, plasma variables, and ruminal bacterial community of growth-retarded lamb.

Introduction: Growth-retarded lambs would reduce the economic incomes of sheep farming. Nutritional interventions are supposed to promote gastrointestinal health and the compensatory growth of growth-retarded lambs. This study evaluated the effects of probiotic supplementation on the growth performance, plasma characteristics and ruminal bacterial community of growth-retarded lambs. Methods: Twenty-four 50-days old male Hu lambs, including 8 healthy lambs (13.2 ± 1.17 kg) and 16 growth-retarded lambs (9.46 ± 0.81 kg), were used in this study. The 8 healthy lambs were fed the basal diet and considered the positive control (GN), and the other 16 growth-retarded lambs were randomly assigned into 2 groups (basal diet without probiotic [negative control, GR] and basal diet supplementation with 1 g/kg concentrate feed probiotic [GRP]), with each group having 4 replicate pens. The feeding trial lasted for 60 days with 7 days for adaptation. Results: The results showed that dietary supplementation with probiotic increased (p < 0.05) the average daily gain and dry matter intake of growth-retarded lambs. For growth-retarded lambs, supplementation with probiotic increased (p < 0.05) the activities of superoxide dismutase and glutathione peroxidase, as well as the concentrations of growth hormone and immunoglobulin G. Furthermore, the highest (p < 0.05) concentrations of interleukin-6, interferon-gamma and tumor necrosis factor alpha were observed in the GR group. The concentrations of total volatile fatty acids and acetate in growth-retarded lambs were increased by probiotic supplementation (p < 0.05). The relative abundances of Ruminococcus, Succiniclasticum and Acidaminococcus were lower (p < 0.05) in growth-retarded lambs. However, probiotic supplementation increased (p < 0.05) the relative abundances of these three genera. Discussion: These results indicate that dietary supplementation with probiotic are promising strategies for improving the growth performance of growth-retarded lambs by enhancing immunity and altering the ruminal microbiota.

Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds.

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.

Supramolecular self-assembled AIE molecules are used in the search for target proteins in norcantharidin.

Norcantharidin (NCTD), a demethylated derivative of cantharidin, is an anticancer active component in traditional Chinese medicine. At present, the main methods for finding its target proteins are pharmacological methods and biophysical screening, which cannot achieve the purpose of efficient and accurate screening. Here we established a new analytical method for specific fishing and assisted imaging for norcantharidin target proteins. For the AIE supramolecule probe, the benzophenone azide (BPA) fluorescent nanoparticles with strong AIE properties were encapsulated in biocompatible DSPE-PEG that covalently coupled with NCTD (named BPA@NCTD NPs). The target proteins of NCTD can be captured by BPA@NCTD NPs, and then be detected to investigate the potential signaling pathways. The screened differential proteins were analysed through the protein and signaling pathway database, and multiple signaling pathways were obtained and verified. The mechanism of norcantharidin in inhibiting the migration and invasion of A549 cells through the P53 signaling pathway was confirmed by Western blot experiments. Our research showed that AIE supramolecule probe BPA@NCTD NPs has the dual functions of specific screening of A549 cells target proteins and biological imaging, which not only offers a good anti-fluorescence quenching ability for the dynamic imaging process of NCTD, but also provides a novel and efficient specific method for efficient analysis of target proteins and signal pathways.

Leucine protects bovine intestinal epithelial cells from hydrogen peroxide-induced apoptosis by alleviating oxidative damage.

BACKGROUND: The present study aimed to investigate whether leucine (Leu) alleviates oxidative injury in bovine intestinal epithelial cells (BIECs) induced by hydrogen peroxide (H2 O2 ), as well as the underlying molecular mechanisms. RESULTS: BIECs were treated with H2 O2 (1 mmol L-1 ) and/or Leu (0, 0.9, 1.8 or 3.6 mmol L-1 ) for 2 h. Leu increased cell viability (P < 0.05) and decreased the release of lactate dehydrogenase (P < 0.05) in BIECs challenged by H2 O2 . Then, the cells were treated with H2 O2 (1 mmol L-1 ) and/or Leu (1.8 mmol L-1 ) for 2 h. Compared with the H2 O2 group, cells treated with Leu and Leu + H2 O2 exhibited increased (P < 0.05) mRNA and protein expression of superoxide dismutase 2 (SOD2), catalase (CAT), glutathione peroxidase 1 (GPx1), heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). BIECs treatment with Leu significantly reduced (P < 0.05) apoptosis induced by H2 O2 . BIECs were transfected with Nrf2 small interfering RNA (siRNA) for 48 h and/or treated with H2 O2 (1 mmol L-1 ) and/or Leu (1.8 mmol L-1 ) for another 2 h. Transfection with Nrf2 siRNA abrogated the protective effect of Leu against H2 O2 -induced apoptosis and the mRNA and protein expression of SOD2 (P < 0.05). CONCLUSION: These results indicate that Leu promotes the relative expression of antioxidant enzymes (SOD2, CAT and GPx1) and phase II detoxification enzymes (HO-1) by upregulating nuclear Nrf2 and activating the Nrf2 signaling pathway, thus enhancing the antioxidant capacity of cells. © 2022 Society of Chemical Industry.

Feasibility of using ammonium iron (II) sulphate to passivate hexavalent chromium in polluted soil.

ABSTRACTThe use of ammonium iron (II) sulphate ((NH4)2Fe(SO4)2) to remediate soil contaminated with Cr (VI) was assessed. (NH4)2Fe(SO4)2 effectively remediated soil contaminated with Cr (VI) and, acted as a fertilizer by supplying nitrogen because it contains ammonium. The effects of the (NH4)2Fe(SO4)2 dose, water content, pH of the soil and the contact time were investigated. The amount of Cr (VI) leached from the most-polluted soil, determined using a leaching toxicity procedure using optimized conditions, was 347.64 mg kg-1 when the soil was untreated and 6.74 mg kg-1 when the soil was treated with (NH4)2Fe(SO4)2. Bio-utilizable Cr contributed 59.44% and 0.16% of the total Cr contents of the untreated and treated soil, respectively. The relatively stable Cr species contributed 24.92% and 98.38% of the total Cr contents of the untreated and treated soil, respectively. The results indicated that adding (NH4)2Fe(SO4)2 markedly decreased the risk of Cr being released from heavily contaminated soil by decreasing the availability of Cr in the soil. Overall, the results indicated that adding (NH4)2Fe(SO4)2 causes some Cr (VI) in contaminated soil to be reduced to Cr (III), and to form a precipitate, which decreases the risk of Cr being released. (NH4)2Fe(SO4)2 can be applied to soil contaminated with Cr (VI) on a large scale because it is cheap and simple to achieve.