Application of MOF-based nanotherapeutics in light-mediated cancer diagnosis and therapy.

Light-mediated nanotherapeutics have recently emerged as promising strategies to precisely control the activation of therapeutic reagents and imaging probe both in vitro and in vivo, largely ascribed to their unique properties, including minimally invasive capabilities and high spatiotemporal resolution. Nanoscale metal-organic frameworks (NMOFs), a new family of hybrid materials consisting of metal attachment sites and bridging ligands, have been explored as a new platform for enhanced cancer diagnosis and therapy due to their tunable size, modifiable surface, good biocompatibility, high agent loading and, most significantly, their ability to be preferentially deposited in tumors through enhanced permeability and retention (EPR). Especially the light-driven NMOF-based therapeutic platform, which not only allow for increased laser penetration depth and enhanced targeting, but also enable imaging-guided or combined treatments. This review provides up-to-date developments of NMOF-based therapeutic platforms for cancer treatment with emphasis on light-triggered therapeutic strategies and introduces their advances in cancer diagnosis and therapy in recent years.

Effects of dietary glucose and starch levels on the growth, apparent digestibility, and skin-associated mucosal non-specific immune parameters in juvenile blunt snout bream (Megalobrama amblycephala).

A 10-week feeding trial was performed to evaluate the effects of different types and levels of carbohydrates in growth performance, apparent digestibility coefficients and skin-associated mucosal non-specific immune parameters in blunt snout bream (Megalobrama amblycephala). Fish were randomly fed four diets containing two carbohydrates (glucose and starch) diets and two carbohydrates levels (330 and 440 g kg-1). High carbohydrate levels remarkably increased the weight gain rate (WGR), apparent digestibility of dry matters, protein and carbohydrates, body crud protein content, plasma levels of aspartate transaminase (AST), and skin-associated mucosal levels of immunoglobulin M (IgM), HDL cholesterol, lysozyme (LZM), advanced the transcriptions of mucin 2 (Muc2), mucin 5b (Muc5b) and apolipoprotein A-I (apoA-I), whereas the opposite was true for feed conversion ratio (FCR), plasma levels of IgM, skin-associated mucosal levels of major histocompatibility complex (MHC) and ß-Defensins, and the transcriptions of heat shock protein 60 (Hsp60). In addition, carbohydrate types of glucose remarkably increased the survival rate, apparent digestibility of dry matters, protein and carbohydartes, body crud ash, plasma levels of total protein (TP), globulin (GLB), immunoglobulin M (IgM), complement C3 and complement C4 and the transcriptions of Muc5b. Whereas the carbohydrate types of starch remarkably increased viscerosomatic index (VSI), hepatosomatic index (HSI), condition factor (CF), abdominal fat percentage (AFP), apparent digestibility of liquid, advanced the transcriptions of Muc2, apoA-I and heat shock protein 70 (Hsp70). Significant interactions between different types and levels of dietary carbohydrates were also observed in WGR, apparent digestibility of dry matters, protein and liquid, body crud ash, plasma levels of TP, albumin (ALB) and AST, skin-associated mucosal levels of major histocompatibility complex (MHC) and ß-Defensins, and the transcriptions of Muc2 and Muc5b. Our results indicate that inclusion of high level of glucose in the diet of blunt snout bream could improve growth performance, nonspecific immunity, and increase the efficiency of protein, which is suggesting that high level of glucose could be used in feed production. However, the proportion of the specific formula of glucose using in feed needs further study.

Fishmeal replacement by rice protein concentrate with xylooligosaccharides supplement benefits the growth performance, antioxidant capability and immune responses against Aeromonas hydrophila in blunt snout bream (Megalobrama amblycephala).

This study aimed to investigate the effects of fishmeal (FM) replacement by rice protein concentrate (RPC) with a xylooligosaccharides supplement on the growth performance, antioxidant capability and immune response against Aeromonas hydrophila in blunt snout bream (Megalobrama amblycephala). Fish (46.85 ±â€¯0.34 g) were randomly assigned to one of 6 diets, namely the control diet (containing FM), the RPC diet (FM replaced by RPC) and RPC diet supplemented with 0.5, 1.5, 2.3 and 3% XOS respectively, for 8 weeks. After the feeding trial, fish were challenged by Aeromonas hydrophila for 96 h with the blood and liver sample obtained at 48 and 96 h respectively. The results showed that the final weight, weight gain and protein efficiency ratio of fish fed RPC diet were significantly (P < 0.05) lower than that of the control group, whereas the opposite was true for FCR. However, the supplement of 1.5% XOS remarkably (P < 0.05) improved these parameters compared to the control diet. Plasma total iron binding capacity of fish fed the RPC diet showed little difference (P > 0.05) with that of the control group, but it enhanced significantly (P < 0.05) with the supplement of 1.5% XOS compared to the control group. After bacterial infection, plasma lysozyme (LYM), complement 3, complement 4, myeloperoxidase (MPO), acid phosphatase (ACP) and alkaline phosphatase activities, as well as immunoglobulin M, levels all increased significantly (P < 0.05) with the maximum value is attained at 48 h, then they decreased significantly (P < 0.05) with further increasing time at 96 h. Similar results were also observed in liver superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities as well as malondialdehyde (MDA) content. Regarding dietary treatment, these parameters of fish fed RPC diet showed little difference (P > 0.05) with those fed the control diet but were significantly enhanced (P < 0.05) when RPC diet was supplemented with 1.5-2.3% XOS, except for hepatic (MDA) content which showed an opposite trend compared to the control group. After 96 h of challenge, the relative percentage survival (RPS) of fish fed XOS was significantly higher (P < 0.05) than that of fish offered the control and RPC diet. In addition, significant (P < 0.05) interactions between dietary XOS and sampling time were also observed in plasma LYM, MPO, ACP, and hepatic SOD, CAT, GPX, MDA, as well as RPS. In conclusion, this study indicated that dietary supplementation of 1.5%XOS could significantly improve the growth performance, antioxidant capability, innate immunity and A. hydrophila resistance of blunt snout bream fed diets with FM replaced by RPC.

Molecular characterization of AMP-activated protein kinase α2 from herbivorous fish Megalobrama amblycephala and responsiveness to glucose loading and dietary carbohydrate levels.

This study aimed to characterize the full-length cDNA of AMPKα2 in Megalobrama amblycephala, and evaluate its potential role in glucose homeostasis and carbohydrate metabolism. The cDNA obtained covered 1942bp with an open reading frame of 1635bp encoding 545 amino acids. Multiple alignments and phylogenetic analysis revealed a high homology (91-100%) among most fish and higher vertebrates. This AMPKα2 mRNA predominantly expressed in muscle, liver and brain, while little in gill and intestine. Then, the AMPKα2 expressions were determined in the muscle, liver and brain of fish subjected to a glucose load (injected intraperitoneally with 0, 1.67 and 3.34g glucose per kg body weight) and after a 12-week feeding trial (fed two dietary carbohydrate levels: 30% and 43%), respectively. After the glucose load, plasma glycemia peaked at 1h in fish. Thereafter, it decreased significantly to the basal level at 8h. However, AMPKα2 expression in muscle, liver and brain all decreased significantly during the first 2h, then returned to the basal value at 24h. Unlikely, tissue AMPKα2 expression of fish receiving saline solution increased significantly during the whole sampling period. Additionally, high-carbohydrate diet enhanced its expression in liver and muscle, but not that in brain. These findings indicated that the AMPKα2 gene shared a high degree of conservation with that of the other vertebrates. Muscle, liver and brain AMPKα2 expressions were highly induced by glucose administration. Furthermore, high dietary carbohydrate modified its expressions in these tissues.

The influence of various feeding patterns of emodin on growth, non-specific immune responses, and disease resistance to Aeromonas hydrophila in juvenile Wuchang bream (Megalobrama amblycephala).

The present study was conducted to evaluate the effect of various feeding patterns of emodin on growth, non-specific immune response, and disease resistance to Aeromonas hydrophila in juvenile Wuchang bream. Healthy Megalobrama amblycephala (initial weight: 3.47 ± 0.032) were grown in a circulating water system for 8 weeks. Five groups were studied: one control group was fed with a basal diet for eight weeks (Pattern 1, P1), and three treatment groups were fed with a trial diet of 30 mg emodin kg(-1) at one-week (Pattern 2, P2), two-week (Pattern 3, P3), four-week (Pattern 4, P4) intervals. The final treatment group maintained the trial diet for the entire eight-week study duration (Pattern 5, P5). Results indicated that different feeding patterns of emodin significantly influenced the weight gain rate of Wuchang bream (P < 0.05). Fish in the P4 treatment group had significantly higher rates of weight gain (WG) than those in other treatment groups. There were no significant differences in survival rates or feed conversion ratios (FCR) between treatment groups and the control group. White blood cell count (WBC), respiratory burst activity, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were shown to increase at first and then decrease from P3 condition to P5 condition. Fish under P4 treatment showed the most significant improvement of all tested parameters compared to control. Significantly higher levels (P < 0.05) of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were observed in P2 and P4 treatment groups when compared with the control group, while no significant differences were observed in the AST and ALT activity of fish in P2, P3, P4 and P5 treatment groups. In a bacterial challenge experiment with A. hydrophila, fish under P4 and P5 treatment showed lower cumulative mortality than the control group. The results of this study suggest that an initial 4-week feeding interval is recommended for the economic and practical culture of M. amblycephala.