Maternal Vitamin D3 Supplementation in an Oxidized-Oil Diet Protects Fetus from Developmental Impairment and Ameliorates Oxidative Stress in Mouse Placenta and Fetus.

BACKGROUND: Fried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. OBJECTIVES: This study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. METHODS: Pregnant mice were randomly assigned into 3 groups: Control group (diet with fresh soybean oil), OSO group [diet with oxidized soybean oil (OSO)], and OSOV group (diet with OSO and 10,000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. RESULTS: Maternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase, and inducible nitric oxide synthase, whereas VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor in the placenta. CONCLUSIONS: Maternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VD receptor/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii.

BACKGROUND: Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non-toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii, and their structural features and bioactivity were studied and compared. RESULTS: The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type-I rhamnogalacturonan (RG-I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)-II side chains in the RG-I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti-inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION: This study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Elucidating the Mechanism of Action of the Gram-Negative-Pathogen-Selective Cyclic Antimicrobial Lipopeptide Brevicidine.

Due to the accelerated appearance of antimicrobial-resistant (AMR) pathogens in clinical infections, new first-in-class antibiotics, operating via novel modes of action, are desperately needed. Brevicidine, a bacterial nonribosomally produced cyclic lipopeptide, has shown potent and selective antimicrobial activity against Gram-negative pathogens. However, before our investigations, little was known about how brevicidine exerts its potent bactericidal effect against Gram-negative pathogens. In this study, we find that brevicidine has potent antimicrobial activity against AMR Enterobacteriaceae pathogens, with MIC values ranging between 0.5 µM (0.8 mg/L) and 2 µM (3.0 mg/L). In addition, brevicidine showed potent antibiofilm activity against the Enterobacteriaceae pathogens, with the same 100% inhibition and 100% eradication concentration of 4 µM (6.1 mg/L). Further mechanistic studies showed that brevicidine exerts its potent bactericidal activity by interacting with lipopolysaccharide in the outer membrane, targeting phosphatidylglycerol and cardiolipin in the inner membrane, and dissipating the proton motive force of bacteria. This results in metabolic perturbation, including the inhibition of ATP synthesis; the inhibition of the dehydrogenation of NADH; the accumulation of reactive oxygen species in bacteria; and the inhibition of protein synthesis. Finally, brevicidine showed a good therapeutic effect in a mouse peritonitis-sepsis model. Our findings pave the way for further research on the clinical applications of brevicidine to combat prevalent infections caused by AMR Gram-negative pathogens worldwide.

Synthesis of structurally diverse derivatives of aconitine-type diterpenoid alkaloids and their anti-proliferative effects on canine breast cancer cells.

As one of the most common malignancies in female dogs, no drugs have been developed specifically for the treatment of canine mammary carcinoma. In our previous study, a series of diterpenoid alkaloids derivatives were synthesized and exhibited good anti-proliferative activity in vitro against both normal and adriamycin-resistant human breast cancer cells lines. In this study, a series of structurally diverse aconitine-type alkaloids derivatives were also synthesized basing on the minimal modification principle, by modifying on A-ring, C-ring, D-ring, N-atom or salt formation on aconitine skeleton. Their anti-proliferative effects and mechanism on canine mammary cancer cells were investigated, exhibiting the importance of the substitution at A ring, the long chain ester at the C8, the hydroxyl group at the C13, the phenyl ring at the C14 and the N-ethyl group, while the methoxy group at the C1 and C16 showed little effect on the activity. The results of the proliferation, apoptosis and ultrastructure tests of the treated canine mammary carcinoma cells referred that the representative compound, aconitine linoleate (25) could block the cell cycle of canine mammary carcinoma cells in the G0/G1 phase, and exhibit the anti-proliferative effect by inducing apoptosis.

Effects of Solid Fermentation on Polygonatum cyrtonema Polysaccharides: Isolation, Characterization and Bioactivities.

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.

Isolation, structure identification, and immunostimulatory effects in vitro and in vivo of polysaccharides from Onosma hookeri Clarke var. longiforum Duthie.

BACKGROUND: This study characterized an acidic polysaccharide (OHC-LDPA) isolated from the medicinal and edible homologous plant Onosma hookeri Clarke var. longiforum Duthie. The structure of OHC-LDPA was elucidated based on the analysis of infrared, one-/two-dimensional nuclear magnetic resonance, and gas chromatography-mass spectrometry data. The immunostimulatory effects of OHC-LDPA were identified by both in vitro and in vivo models. RESULTS: The structure of OHC-LDPA was elucidated as a typical pectin polysaccharide, consisting of galacturonic acid, galactose, arabinose, and rhamnose as the primary sugars, with linear galacturonic acid as the main chain and arabinogalacturonic acid as the main branched components. OHC-LDPA could significantly stimulate the proliferation and phagocytosis of RAW264.7 macrophages and the release of nitric oxide in vitro. Also, it could accelerate the recovery of spleen and thymus indexes, enhance the splenic lymphocyte proliferation responses, and restore the levels of interleukin-2, interleukin-10, interferon-γ, and immunoglobulin G in the serum in a cyclophosphamide-induced immunosuppressed-mice model. In addition, OHC-LDPA could restore the intestinal mucosal immunity and reduce the inflammatory damage. CONCLUSION: OHC-LDPA could improve the immunity both in vitro and in vivo and could be used as a potential immunostimulant agent. © 2022 Society of Chemical Industry.

Insights into the Anti-inflammatory and Antiviral Mechanisms of Resveratrol.

Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol's anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded.

Loss of TRIM67 Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease.

Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. Here, we report a tripartite motif (TRIM) protein family member-TRIM67-that is hardly expressed in liver but is inducible on obese conditions. Enhanced expression of TRIM67 activates hepatic inflammation to disturb lipid metabolic homeostasis and promote the progress of NAFLD induced by obesity, while the deficiency in TRIM67 is protective against these pathophysiological processes. Finally, we show that the important transcription coactivator PGC-1α implicates in the response of hepatic TRIM67 to obesity.

The Antivirulence Activity of Umbelliferone and Its Protective Effect against A. hydrophila-Infected Grass Carp.

A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection.

Polysaccharide from Salviae miltiorrhizae Radix et Rhizoma Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease through Modulating Intestinal Microbiota-Related Gut-Liver Axis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut-liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.