Novel albumin-binding multifunctional probe for synergistic enhancement of FL/MR dual-modal imaging and photothermal therapy

The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility. Albumin can protect GIAs from the recognition and clearance by the mononuclear phagocytic system (MPS). High plasma concentration and long half-life allow GIAs to accumulate continuously in the tumor area through EPR effect and specific uptake of tumor. Because of the prolonged rotational correlation time (τR) of Gd chelates, GIAs exhibited superior MR contrast performance over GIs with more than 3 times enhancement of longitudinal relaxation efficiency (r1). The fluorescence quantum yield and photothermal conversion efficiency of GIAs was also significantly improved due to the constrained geometry, disrupted aggregation and enhanced photothermal stability. This simple and feasible strategy successfully resulted in a synergistic effect for FL/MR dual-modal imaging and photothermal therapy, which can cast a new light for the clinical translation of multifunctional probes

Ergothioneine Production by Submerged Fermentation of a Medicinal Mushroom <i>Panus conchatus</i>

Ergothioneine is a natural and safe antioxidant that plays an important role in anti-aging and the prevention of various diseases. This study aimed to report on a kind of medicinal mushroom of Panus conchatus with great potential for the bioproduction of ergothioneine. The effect of different nutritional and environmental conditions on the growth of Panus conchatus and ergothioneine production were investigated. Molasses and soy peptone were found to promote cell growth of Panus conchatus and enhance ergothioneine accumulation. Adding precursors of histidine, methionine and cysteine could increase ergothioneine production and the highest ergothioneine concentration of 148.79 mg/L was obtained. Finally, the extraction and purification processes were also established to obtain the crude ergothioneine extract for further antioxidant property evaluation. The ergothioneine from Panus conchatus showed high antioxidant activity with good stability in a lower pH environment. This study provided a new strain and process for the bioproduction of ergothioneine

Ergothioneine Production by Submerged Fermentation of a Medicinal Mushroom Panus conchatus

Ergothioneine is a natural and safe antioxidant that plays an important role in anti-aging and the prevention of various diseases. This study aimed to report on a kind of medicinal mushroom of Panus conchatus with great potential for the bioproduction of ergothioneine. The effect of different nutritional and environmental conditions on the growth of Panus conchatus and ergothioneine production were investigated. Molasses and soy peptone were found to promote cell growth of Panus conchatus and enhance ergothioneine accumulation. Adding precursors of histidine, methionine and cysteine could increase ergothioneine production and the highest ergothioneine concentration of 148.79 mg/L was obtained. Finally, the extraction and purification processes were also established to obtain the crude ergothioneine extract for further antioxidant property evaluation. The ergothioneine from Panus conchatus showed high antioxidant activity with good stability in a lower pH environment. This study provided a new strain and process for the bioproduction of ergothioneine

Mechanism of Arachidonic Acid Accumulation during Aging in Mortierella alpina: A Large-Scale Label-Free Comparative Proteomics Study

Arachidonic acid (ARA) is an important polyunsaturated fatty acid having various beneficial physiological effects on the human body. The aging of Mortierella alpina has long been known to significantly improve ARA yield, but the exact mechanism is still elusive. Herein, multiple approaches including large-scale label-free comparative proteomics were employed to systematically investigate the mechanism mentioned above. Upon ultrastructural observation, abnormal mitochondria were found to aggregate around shrunken lipid droplets. Proteomics analysis revealed a total of 171 proteins with significant alterations of expression during aging. Pathway analysis suggested that reactive oxygen species (ROS) were accumulated and stimulated the activation of the malate/pyruvate cycle and isocitrate dehydrogenase, which might provide additional NADPH for ARA synthesis. EC 4.2.1.17-hydratase might be a key player in ARA accumulation during aging. These findings provide a valuable resource for efforts to further improve the ARA content in the oil produced by aging M. alpina

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice

Sepsis is extremely heterogeneous pathology characterized by complex metabolic changes. Fibroblast growth factor 19 (FGF19) is a well-known intestine-derived inhibitor of bile acid biosynthesis. However, it is largely unknown about the roles of FGF19 in improving sepsis-associated metabolic disorder and organ injury. In the present study, mice were intravenously injected recombinant human FGF19 daily for 7 days followed by lipopolysaccharide (LPS) administration. At 24 hours after LPS stimuli, sera were collected for metabolomic analysis. Ingenuity pathway analysis (IPA) network based on differential metabolites (DMs) was conducted. Here, metabolomic analysis revealed that FGF19 pretreatment reversed the increase of LPS-induced fatty acids. IPA network indicated that altered linoleic acid (LA) and gamma-linolenic acid (GLA) were involved in the regulation of oxidative stress and mitochondrial function and were closely related to reactive oxygen species (ROS) generation. Further investigation proved that FGF19 pretreatment decreased serum malondialdehyde (MDA) levels and increased serum catalase (CAT) levels. In livers, FGF19 suppressed the expression of inducible NO synthase (iNOS) and enhanced the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and hemeoxygenase-1 (HO-1). Finally, FGF19 pretreatment protected mice against LPS-induced liver, ileum, and kidney injury. Taken together, FGF19 alleviates LPS-induced organ injury associated with improved serum LA and GLA levels and oxidative stress, suggesting that FGF19 might be a promising target for metabolic therapy for sepsis

Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism

The unicellular heterotrophic thraustochytrids are attractive candidates for commercial polyunsaturated fatty acids (PUFA) production. However, the reactive oxygen species (ROS) generated in their aerobic fermentation process often limits their PUFA titer. Yet, the specific mechanisms of ROS involvement in the crosstalk between oxidative stress and intracellular lipid synthesis remain poorly described. Metabolic engineering to improve the PUFA yield in thraustochytrids without compromising growth is an important aspect of economic feasibility. To fill this gap, we overexpressed the antioxidative gene superoxide dismutase (SOD1) by integrating it into the genome of thraustochytrid Schizochytrium sp. PKU#Mn4 using a novel genetic transformation system. This study reports the ROS alleviation, enhanced PUFA production and transcriptome changes resulting from the SOD1 overexpression. SOD1 activity in the recombinant improved by 5.2–71.6% along with 7.8–38.5% decline in ROS during the fermentation process. Interestingly, the total antioxidant capacity in the recombinant remained higher than wild-type and above zero in the entire process. Although lipid profile was similar to that of wild-type, the concentrations of major fatty acids in the recombinant were significantly (p ≤ 0.05) higher. The PUFA titer increased up to 1232 ± 41 mg/L, which was 32.9% higher (p ≤ 0.001) than the wild type. Transcriptome analysis revealed strong downregulation of genes potentially involved in β-oxidation of fatty acids in peroxisome and upregulation of genes catalyzing lipid biosynthesis. Our results enrich the knowledge on stress-induced PUFA biosynthesis and the putative role of ROS in the regulation of lipid metabolism in oleaginous thraustochytrids. This study provides a new and alternate strategy for cost-effective industrial fermentation of PUFA. Keywords: Polyunsaturated fatty acids, Schizochytrium sp., Superoxide dismutase, Transgene, Transcriptomic analysi