Nickel-Catalyzed Radical Ring-Opening Phosphorylation of Cycloalkyl Hydroperoxides Leading to Distal Acylphosphine Oxides.

A facile and efficient nickel-catalyzed C-C bond cleavage/phosphorylation of various cycloalkyl hydroperoxides was developed. This radical ring-opening strategy provided practical access to structurally diverse distal ketophosphine oxides in one pot through concurrent C═O/C-P bond formation with high atom economy under mild room temperature and base-free conditions.

Ovalbumin fibril-stabilized oleogel-based Pickering emulsions improve astaxanthin bioaccessibility.

The present study aimed to enhance the bioaccessibility of hydrophobic astaxanthin (AST) by developing food-grade emulsion systems. Ovalbumin (OVA) fibrils and candelilla wax-based oleogels were prepared for the next fabrication of AST-loaded oleogel-based Pickering emulsions. The food-grade oleogel was obtained by mixing 0.7% (w/w) candelilla wax and soybean oil. The nano-scale OVA fibrils were observed by transmission electron microscope. SDS-PAGE analysis of OVA fibrils displayed the appearance of peptides with molecular weight around 10 kDa. Contact angle measurement indicated that excellent amphiphilicity endowed OVA fibrils with satisfactory Pickering emulsifier performance. The obtained oleogel-based Pickering emulsions displayed ultrastability during 90-day storage and outstanding freeze-thaw stability. Furthermore, the superiority of AST-loaded oleogel-based Pickering emulsion was further reflected in the apparently ameliorative lipolysis extent and AST bioaccessibility compared with oleogel. This work would facilitate the utilization of OVA and the development of oleogel-based Pickering emulsions with desirable nutraceutical bioaccessibility.

Modulation of Fabrication and Nutraceutical Delivery Performance of Ovalbumin-Stabilized Oleogel-Based Nanoemulsions via Complexation with Gum Arabic.

Protein-polysaccharide complexes, which involve Maillard-type protein-polysaccharide conjugates and electrostatic protein-polysaccharide complexes, have the potential to stabilize oleogel-based nanoemulsions for nutraceutical delivery. Here, ovalbumin (OVA) and gum arabic (GA) were used to prepare OVA-GA conjugate (OGC) and OVA-GA mixture (OGM), followed by the fabrication of astaxanthin-loaded oleogel-based nanoemulsions. Carnauba wax (5% w/w) and rice bran oil were mixed to prepare food-grade oleogel. The successful preparation of OGC was verified by means of SDS-PAGE analysis and free amino groups determination. OGC endowed oleogel-based nanoemulsions with smaller emulsion droplets and higher stability during 30-day storage, implying more outstanding emulsifying capability than OGM. Both OGC-stabilized nanoemulsions and OGM-stabilized nanoemulsions could enhance the extent of lipolysis and the bioaccessibility of astaxanthin compared with oleogel. Meanwhile, OGC exhibited significantly better than OGM, which indicated that OGC-stabilized oleogel-based nanoemulsions possessed more desirable nutraceutical delivery performance than OGM-stabilized oleogel-based nanoemulsions. This study may fill a gap in the influence of different protein-polysaccharide complexes on oleogel-based nanoemulsions and contribute to deeper insights about novel oleogel-based nanoemulsions for their applications in the food industry.

Lactoferrin particles assembled via transglutaminase-induced crosslinking: Utilization in oleogel-based Pickering emulsions with improved curcumin bioaccessibility.

In this study, the optimal environmental condition for preparation of lactoferrin particles assembled via transglutaminase-induced crosslinking (TG-LF particles) was pH 8, 100 U/g of TG concentration, 50 °C and 2 h of crosslinking time. Contact angle of TG-LF particles was 79°. Then, corn oil-based oleogels were prepared with carnauba wax (CW), behenyl alcohol (BA) and CW-BA mixture at 1:4 ratio (MT). To investigate the effect of oleogels on oleogel-based Pickering emulsions, oleogel-based Pickering emulsions were prepared by a two-step method using different oleogels as the oil phase and the TG-LF particles as the emulsifier. In vitro digestion study revealed that CW oleogel-based Pickering emulsion had the highest lipolysis rate and curcumin bioaccessibility. This study demonstrated that TG-LF particle-stabilized oleogel-based Pickering emulsions had good performance in curcumin delivery, which provided a new idea for the preparation of Pickering emulsifier and enriched the knowledge in the field of oleogel-based Pickering emulsion.

Palladium-catalyzed C-P cross-coupling of allenic alcohols with H-phosphonates leading to 2-phosphinoyl-1,3-butadienes.

The first facile, efficient, atom-economical and regioselective palladium-catalyzed direct C-P cross-coupling of unprotected allenic alcohols with H-phosphonates for the one-pot synthesis of structurally diverse multisubstituted 2-phosphinoyl-1,3-butadienes was developed. This strategy would enrich the allene chemistry and afford new scaffolds to construct complex molecular skeletons.

The differential expression and potential roles of circular RNAs in children with anti-NMDA receptor encephalitis.

To explore the role of circular RNAs (circRNAs) in pediatric anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, we assessed the profiles of circRNAs and mRNAs in blood leukocytes from anti-NMDA receptor encephalitis patients and healthy controls using microarray analysis. 1196 circRNAs and 719 mRNAs (change ≥2, p < .05) were dysregulated in anti-NMDA receptor encephalitis patients, relative to healthy controls, based on microarray data. Further bioinformatic analysis demonstrated that the host genes of dysregulated circRNAs are primarily associated with receptor internalization. In conclusion, circRNAs may be implicated in the pathogenesis of pediatric anti-NMDA receptor encephalitis.

Copper-Catalyzed Direct Twofold C-P Cross-Coupling of Unprotected Propargylic 1,4-Diols: Access to 2,3-Bis(diarylphosphynyl)-1,3-butadienes.

The first facile and efficient Cu-catalyzed direct coupling of unprotected propargylic diols with H-phosphine oxides was developed, providing a practical approach to access structurally diverse 2,3-bis(diarylphosphynyl)-1,3-butadienes along with the formation of two new P-Csp2 and two new C═C bonds under ligand- and base-free conditions.

Eriodictyol Attenuates LPS-Induced Neuroinflammation, Amyloidogenesis, and Cognitive Impairments via the Inhibition of NF-κB in Male C57BL/6J Mice and BV2 Microglial Cells.

Eriodictyol, a natural flavonoid mainly distributed in citrus fruits and peanut, has been well-documented with possession of excellent anti-inflammatory, antioxidant, and anticancer bioactivities. This work focus on the protective effects of eriodictyol on LPS-induced neuroinflammation, amyloidogenesis, cognitive impairment, and the potential mechanisms involved. Behavioral tests and histological examinations showed that eriodictyol significantly prevented the memory and neuronal damage triggered by LPS. Consistently, eriodictyol (100 mg/kg) reduced the formation of Aß1-42 by 28.37 ± 16.71 pg/mL compared to the LPS group. In addition, high dose eriodictyol (100 mg/kg) also equilibrated the cholinergic system via suppressing AChE activity (0.1996 ± 0.0831 U/mgprot) and elevating ChAT activity (41.81 ± 24.72 U/g) as well as ACh level (5.093 ± 3.531 µg/mgprot) compared to the LPS group. Western blot results indicated that compared to the LPS group, eriodictyol suppressed LPS-induced glial overactivation (84.29% ± 27.21%) and regulated inflammatory mediators and cytokines by inhibiting the NF-κB and MAPK pathways. These results indicated that eriodictyol alleviated amyloidogenesis and memory impairment triggered by LPS via inhibiting TLR4, MAPKs, and PI3K/Akt, and activating Sirt1 pathways and thus blocking downstream translocation of NF-κB, which offers a potential nutritional preventive strategy for neuroinflammation diseases such as Alzheimer's disease (AD).

Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

Nickel-catalyzed one-pot tandem 1,4-1,2-addition of P(O)H compounds to 1,10-phenanthrolines.

A novel and efficient nickel-catalyzed tandem 1,4-1,2-addition of P(O)H compounds to 1,10-phenanthrolines forming various 2,4-diphosphono-1,2,3,4-tetrahydro-1,10-phenanthrolines has been developed. This reaction breaks up the aromatic stabilization and directly introduces two phosphorus moieties in one single step. This finding is the first example of transition-metal-catalyzed double hydrophosphonylation of 1,10-phenanthrolines.

Nickel-catalyzed decarboxylative C-P cross-coupling of alkenyl acids with P(O)H compounds.

The first nickel-catalyzed decarboxylative C-P coupling of a wide range of alkenyl acids with various P(O)H compounds, especially for H-phosphonates, has been developed, affording a versatile and efficient tool for the preparation of valuable (E)-1-alkenylphosphonates, (E)-1-alkenylphosphinate oxides, and (E)-1-alkenylphosphine oxides with high stereoselectivity and broad substrate applicability. DFT calculation revealed that the phosphine ligand exhibits better catalytic performance than the nitrogen ligand in the reductive elimination step owing to the stronger nucleophilicity and larger size.

Nickel-catalyzed C-P cross-coupling of arylboronic acids with P(O)H compounds.

A novel and efficient Ni-catalyzed coupling of a wide range of arylboronic acids with H-phosphites, H-phosphinate esters, and H-phosphine oxides has been developed, providing a general and powerful tool for the synthesis of various aryl-phosphorus compounds, especially for valuable triarylphosphine oxides, in good to excellent yield. This protocol is the first Ni-catalyzed C-P bond-forming reaction between arylboronic acids and P(O)H compounds.

[Therapeutic mechanisms of interferon-beta and intravenous immunoglobulin for experimental peripheral neuropathy].

OBJECTIVE: To explore the therapeutic mechanisms of interferon-beta (IFN-beta) and intravenous immunoglobulin (IVIG) for experimental peripheral neuropathy induced by Campilobacter jejuni (Cj) lipopolysaccharide (LPS). METHOD: Forty healthy Wistar rats weighing 205 - 230 g were divided into IFN-beta, IVIG, IFN-beta plus IVIG and control groups. After the immune neuropathy was induced in the rats by Cj LPS, IFN-beta (1.3 microg/kg) was given by subcutaneous injection to the rats every other day for 6 weeks; IVIG [400 mg/(kg x d)] was given to the rats for five days, every other week for two times and IFN-beta [1.3 microg/(kg x d)] and IVIG [400 mg/(kg x d)] were given to the rats on the same days. Meanwhile, the control group was given PBS. The sera were collected in the 2nd, 4th and 6th week after therapy, the titers of anti-GM(1) IgG, MMP-9 and TNF-alpha in sera of immunized rats were measured by ELISA; histological study of sciatic nerve was performed and IgG on sciatic nerve was detected by immunohistochemistry in the 6th week. RESULTS: (1) There were no significant differences in titers of anti-GM(1) IgG, MMP-9 and TNF-alpha among the 3 therapeutic groups and control group after therapy for 2 weeks (P > 0.05). (2) The titers of anti- GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta and IVIG group after therapy for 4 weeks (P > 0.01) and there were no significant differences in titers of antibody among the 3 therapeutic groups (P > 0.05); the titers of MMP-9 or TNF-alpha in the IFN-beta and IVIG group were lower than those of the IFN-beta group or the IVIG group (P < 0.05). (3) The titers of anti-GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta with IVIG group after therapy for 6 weeks (P > 0.01); the IFN-beta with IVIG group had much lower levels of all indexes than the IFN-beta group or the IVIG group (P < 0.01). CONCLUSION: IFN-beta and IVIG showed therapeutic effects on immune peripheral neuropathy through inhibiting the humoral and cellular immunity simultaneously in the peripheral neuropathy induced by CJ LPS, treatment with combined IFN-beta and IVIG was more effective.

[Damage to peripheral nerves induced by Campylobacter jejuni exotoxin].

OBJECTIVE: To explore the pathogenesis of the damage to peripheral nerves induced by Campylobacter jejuni exotoxin (CJT). METHODS: (1) Animal models: (1) The CJT was extracted from PEN 19-CJ and injected perineurally and intravenously to Wistar rats. (2) The sera and the supernatants of peripheral blood mononuclear cells (PBMCs), taken from the rats immunized with the CJT, were injected perineurally at sciatic nerves of experimental rats and intravenously, respectively. (2) Histopathologic study of sciatic nerves: the animals were sacrificed and their sciatic nerves were examined for tease fibers, transverse section with toluidine blues staining and electron microscopy. (3) Immunohistochemistry: sections of sciatic nerves of either normal rats or human which were incubated with CJT and the sciatic nerves with pathological changes induced by CJT were obtained for observation of the binding capability of CJT with peripheral nerves by SABC and FITC-immunofluorescence methods, and nucleic acid hybridization techniques for detection of TNF-alpha mRNA expression in pathological sciatic nerves samples. RESULTS: (1) Remarkable peripheral neuropathies with axon degeneration and/or demyelination were found in the nerves induced by both CJT injection perineurally and intravenously. The axon degeneration was more obvious. Pathological changes were identified in 76.8% (2,763/3,600) of teasing fibers after perineural injection, but only 9.6% (230/2,400) of fibers were damaged in control group (P < 0.01). The peak severity of fiber damage was found on the 3rd day after CJT intravenous injection with the incidence of abnormal fibers was 19.5% (390/2,000), and abnormalities of 15.5% (310/2000) on the 14th day. However, no abnormal changes were demonstrated in control group (P < 0.01). So was in the groups injected with anti-CJT sera and the supernatants of PBMCs compared with control (P > 0.05). (2) Binding of CJT to the nerve was found dominant in the sciatic nerves taken from normal rats or human either incubated with CJT or in the pathological sciatic nerves induced by CJT to various degrees. The binding of CJT to all these nerves was determined. (3) After intravenous injection with CJT, no histopathologic change could be found in the other viscera of the rats, with the exception of remarkable pathological change in peripheral nerves. CONCLUSIONS: (1) CJT could remarkably damage the peripheral nerves in rats. Specific pathogenicity of CJT to peripheral nerves was well shown, because no histopathologic abnormalities could be found in the other viscera, such as brain, liver and kidney etc. although there was remarkable pathological change along the peripheral nerve in the animals. (2) No immunological pathogenicity of CJT could be demonstrated in the nerves of rats after immunization with CJT.

[Experimental study on the therapeutic mechanism of high dose intravenous immunoglobulin in treatment of immune-mediated peripheral neuropathy].

OBJECTIVE: To explore the therapeutic basis of high dose intravenous immunoglobulin (IVIg) in treatment of peripheral neuropathy induced by Campylobacter jejuni lipopolysaccharide (CJ LPS). METHOD: (1) IVIg (400 mg/kg x d) was given to the rats on the different days respectively during the immunization with CJ LPS. Histological study of sciatic nerve was performed on the 35 th day after immunization. The titer of anti-CJ LPS antibody in sera of immunized rats was measured by ELISA; IgG deposition was detected by immunohistochemistry and expression of TNF-alpha mRNA in the pathological nerves by in situ hybridization histochemistry. (2) When PBMCs were stimulated by CJ LPS in vitro, IVIg was added into culture medium at the doses of 1, 2.5, 5, and 10 mg/ml, respectively. Pathological examination of sciatic nerve was performed on the 7th day after perineural injection of the supernatants. Expression of TNF-alpha mRNA in PBMCs stimulated by CJ LPS in medium was detected by in situ hybridization histochemistry after adding IVIg. RESULTS: (1) The rate of abnormal fibers appearance in IVIg group (1.0%) was much lower than that of the control group (15.0%) after immunization with CJ LPS, P < 0.01. The titer of antibody in control group was 9 times higher than that of IVIg group. There was no expression of immunoglobulin and TNF-alphamRNA in peripheral nerves in IVIg group, but high expression was found in control group in which no IVIg was injected. (2) The expression rates of TNF-alphamRNA on the PBMCs in IVIg group (1.0%) was much lower than that of control group (9.5%). (3) When the PBMCs of normal rats were stimulated by CJ LPS, the expression rates of TNF-alphamRNA in PBMCs of 5 mg/ml IVIg group (3.0%) or 10 mg/ml IVIg group (2.0%) were much lower than that of 1 mg/ml IVIg group (15.0%) or 2.5 mg/ml IVIg group (11.5%), P < 0.01. The rate of abnormal fibers appearance in 5 mg/ml IVIg group (9.8%) or 10 mg/ml IVIg group (8.5%) was much lower than that of 1 mg/ml IVIg group (50.0%), 2.5 mg/ml IVIg group (41.0%) or control group (50.8%) after the perineural injection with the supernatants, respectively, P < 0.01. CONCLUSION: The therapeutic effect of high dose IVIg might be associated with inhibition of the humoral and cellular immunity simultaneously in peripheral neuropathy induced by CJ LPS.