Roles of Gut Microbiota in Pathogenesis of Alzheimer's Disease and Therapeutic Effects of Chinese Medicine.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive impairment. The pathogenesis of AD is complex, and its susceptibility and development process are affected by age, genetic and epigenetic factors. Recent studies confirmed that gut microbiota (GM) might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflflammatory and immune processes. CM formula, herbs, and monomer enjoy unique advantages to treat and prevent AD. Hence, the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD. Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed. The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.

Electrochemical fabrication of reduced MoS2-based portable molecular imprinting nanoprobe for selective SERS determination of theophylline.

A new portable molecular imprinting polymer (MIP)-SERS nanoprobe is fabricated by a convenient electrochemical method. Single-layered MoS2 is electrochemically reduced on a screen-printed electrode as the scaffold. Functional monomers o-phenylenediamine (oPD), template theophylline (THP), and SERS-active Au nanoparticles (AuNPs) are then one-step electropolymerized on the scaffold. The morphology of the nanoprobe is found to be a three-dimensional and porous structure. The abundant AuNPs with the size of 45~50 nm are trapped within the growing MIP instead of being confined to the surface. The thickness of MIP film is calculated to 25.1 nm. The nanoprobe displays a strong SERS effect for THP using 532 nm as excitation wavelength with a detection limit (LOD) of 0.01 nM. The SERS peak intensity at 1487 cm-1 increases linearly with the concentration of THP in the range 0.1 nM to 0.1 mM. After the template is removed, the imprint-removed nanoprobe is generated for selective binding of THP. The re-binding kinetics study implies the portable MIP-SERS nanoprobe can reach the adsorption equilibrium within 8 min. This nanoprobe exhibits low SERS interference for structural analogues theobromine (THB) and caffeine (CAF). The nanoprobe was employed to THP determination in tea drink samples, with recoveries ranging from 99.0 to 102.0% and relative standard deviations of < 5.0%. Graphical abstractSchematic representation of a portable molecular imprinting SERS nanoprobe used for selective and sensitive theophylline recognition. The nanoprobe is fabricated by one-step electropolymerized o-phenylenediamine (oPD), theophylline, and electroreduced Au nanoparticles (AuNPs) on reduced MoS2 (rMoS2) modified screen-printed electrode (SPE).

Copper-mediated cascade radical cyclization of olefins with naphthalenyl iododifluoromethyl ketones.

Copper-mediated radical cyclization of naphthalenyl iododifluoromethyl ketones with olefins was successfully developed to generate a series of unprecedented gem-difluorodihydrophenanthrenones, especially 2,2-difluoro-3,4-dihydrophenanthren-1(2H)-one derivatives. This strategy features the use of cheap copper powder and excellent regioselectivity and diastereoselectivity, thus providing a facile approach for application in drug discovery and development. Preliminary mechanistic studies indicate the involvement of difluorinated radical intermediates. Density functional theory (DFT) calculation was performed to provide further evidence for regioselectivity.

[The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy].

OBJECTIVE: To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA). METHODS: A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyte globulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months. RESULTS: Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values < 0.05). Clinical response rates were comparable in both ATG+CsA or CsA alone groups no matter PNH clone was positive or negative. CONCLUSIONS: PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurred before or after IST does not affect the therapeutic efficacy.

[Changes of transcription factors Bcl-6, Foxp3 and RORγt in CD4(+) cells in bone marrow of immuno-related hematocytopenia].

OBJECTIVE: To evaluate the possible mechanism of transcription factors B cell lymphoma 6 (Bcl-6) , forkhead/winged helix transcription factor 3 (Foxp3) and retinoic acid related orphan receptor (RORγt) in CD4(+) T cells for immuno-related hematocytopenia (IRH). METHODS: CD4(+) T cells were harvested from 40 IRH patients, 38 aplastic anemia subjects and 25 normal controls and separated by magnetic activated cell sorting (MACS). Then the expressions of transcription factors of Foxp3, RORγ and Bcl-6 in CD4(+) T cells were measured by real time fluorescent quantitative-polymerase chain reaction (QRT-PCR). RESULTS: Auto-antibody was detected on CD34(+) cells (67.5% (27/40) ), CD15(+) cells (65.0% (26/40)), GlyA(+) cells (75.0% (30/40) ), auto-antibody involving three, two or one myeloid cell were detected in 27.5% (11/40), 52.5% (21/40), 20.0% (8/40) of IRH patients. Compensatory increase of Foxp3 mRNA was found in IRH (0.124 (0.073-0.198) vs 0.071 (0.046-0.118), P < 0.05). The expression of Bcl-6 was higher (2.243 (0.854-4.544) vs 1.211 (0.131-2.816), P < 0.05). Compared to aplastic anemia, the expression of RORγt was lower in IRH (0.133 (0.068-0.189) vs 0.290 (0.138-0.480), P < 0.01) and the ratio of Treg/Th17 shifted to Th17 in patients with aplastic anemia (Foxp3/RORγt ratio,0.500 (0.240-0.795) vs 0.975 (0.483-1.416), P < 0.01). CONCLUSION: As one kind of bone marrow failures caused by autoantibody to bone marrow cells, IRH may occur due to a high expression of Bcl-6 in CD4(+) T cells, its immunopathogenesis is different from that of aplastic anemia.

[Experimental study on the therapeutic effect of C-phycocyanin against pulmonary fibrosis induced by paraquat in rats].

OBJECTIVE: To investigate the therapeutic effect of C-phycocyanin (C-PC) from Spirulina platensis on paraquat (PQ)-induced pulmonary fibrosis in rats. METHODS: A total of 90 healthy Wistar rats were randomly and equally divided into normal control group, model group (PQ group), and C-PC treatment group (C-PC group). Each rat in the PQ group and C-PC group were orally administered with a single dose of PQ (50 mg/kg) to establish a rat model of PQ poisoning. Then, the rats in the normal control group and PQ group were orally given saline solution (1 ml/100 g) every day, and the rats in the C-PC group were orally given C-PC (50 mg/kg) every day. Six rats were randomly selected from each group on days 1, 3, 7, 14, and 28. The inferior lobe of each rat's right lung was homogenized for the measurement of hydroxyproline (HYP) and maleic dialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Parts of each rat's left lung were subject to HE staining and Masson staining for pathological observation, and the expression of transforming growth factor-ß(1) (TGF-ß(1)), nuclear factor-kappa B p65 (NF-κB p65), and tumor necrosis factor-α (TNF-α) in lung tissue was measured by immunohistochemistry. RESULTS: The HYP levels on days 1, 3, 7, 14, and 28 and MDA levels on days 14 and 28 were significantly lower in the C-PC group than in the PQ group (P < 0.05, P < 0.01). The SOD activity was significantly higher in the C-PC group than in the PQ group on days 1, 7, 14, and 28 (P < 0.05, P < 0.01). The protein content of TGF-ß(1) and the activities of NF-κB p65 and TNF-α in the PQ group and C-PC group were significantly higher than those in the normal control group, while the indices in the C-PC group were significantly lower than those in the PQ group (P < 0.05, P < 0.01). The pathological observation showed that C-PC could alleviate pulmonary alveolitis and fibrosis in rats with PQ poisoning. CONCLUSION: C-PC can significantly inhibit PQ-induced pulmonary alveolitis and fibrosis in rats.

[Advancements in diagnosis and management of paroxysmal nocturnal hemoglobinuria - review].

Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic disease of abnormally activated complement. FLAER diagnosis is a higher sensitive and specific method, which makes PNH patients to be early discovered and treated. Non-typical symptoms including thrombosis, pulmonary hypertension and chronic kidney disease in PNH have been caused increasing attention. Eculizumab monoclonal antibody has greatly improved the current treatment status of PNH. PNH can be cured thoroughly by allogeneic hematopoietic stem cell transplantation. In this article, the FLAER diagnosis, clinic symptoms and progress of treatment in patients with PNH are reviewed.