Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

The immunodominant and neutralization linear epitopes for SARS-CoV-2.

Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses.

[Hair roots induction and culture of Withania somnifera and its withanolide A synthesis].

Withanolide A is a biologically active secondary metabolite occuring in roots and leaves of Withania somnifera. In the present study, adventitious roots from leaf explants of W. somnifera were induced for the production of withanolide-A by Agrobacterium tumefaciens strain C58C1 to obtain hair roots. Hair roots induction rate reached 30%. The withanolide A was determined by HPLC in different hair roots lines and different parts of W. somnifera. The average content of withanolide A in all hair roots lines were 1.96 times as high as that in wild-plant, the concentration of withanolide A in hair roots (1.783 mg x g(-1) dry weight) were 1.51 times as high as the roots of wild W. somnifera (1.180 mg x g(-1) dry weight), respectively. It is possible to obtain withanolide A from hair roots culture of W. somnifera.

[Culture in vitro and plant regeneration of Panax japonicus].

OBJECTIVE: To study the condition of culture in vitro and plant regeneration of Panax japonicus. METHODS: Embryos, stems and leaves of P. japonicus were used as explants, effects of different hormones for callus induction and plant regeneration were studied and optimized. RESULTS: The optimal way to obtain sterile explant for seeds was sterilized in 75% ethyl alcohol for 60 s then 0.1% HgCL2 for 12 min; Stems and leaves were sterilized in 75% ethyl alcohol for 15 s then 5% NaClO for 5 min. Used MS as basic medium, the optimal hormones combination for callus induction of embryos, stems and leaves were MS + 1.5 mg/L NAA + 1.5 mg/L 2, 4-D + 0.1 mg/L KT; MS + 1.5 mg/L NAA + 1.0 mg/L 2,4-D + 0.1 mg/L KT; MS + 1.5 mg/L NAA + 1.0 mg/L 2,4-D + 0.2 mg/L KT respectindy under the illumination. But under the darkness,the optimal callus induction hormones combination for embryos leaves were MS + 1.0 mg/L NAA + 1.5 mg/L 2,4-D +0.2 mg/L KT; 1.5 mg/L NAA + 1.5 mg/L 2,4-D + 0.1 mg/L KT; MS + 1.5 mg/L NAA + 1.0 mg/L 2,4-D + 0.1 mg/L KT respectivety. The optimal medium for germination was MS + 3.0 mg/L 6-BA + 1.0 mg/L GA3. The optimal medium for roots generation was MS + 1.0 mg/L 6-BA + 3.0 mg/L IBA. CONCLUSION: We establish the system of culture in vitro and plant regeneration for P. japonicus.