FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.

FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10(+) CD4(+) T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors

catena-Poly[[(isoquinoline-κN)(triphenylphospane-κP)copper(I)]-μ-thio­cyanato-κ2 N:S]

In the title coordination compound, [Cu(NCS)(C9H7N)(C18H15P)]n, the CuI atom is tetra­hedrally coordinated by one N atom from an isoquinoline ligand, one P atom from a triphenyl­phospane ligand, and one N and one S atom from two thio­cyanate anions. The thio­cyanide anions bridge the CuI atoms into a chain along [100]. π–π inter­actions between the pyridine and benzene rings of the isoquinoline ligands connect the chains [centroid-to-centroid distance = 3.722 (3) Å]

Fasudil in Combination With Bone Marrow Stromal Cells (BMSCs) Attenuates Alzheimer\u27s Disease-Related Changes Through the Regulation of the Peripheral Immune System.

Alzheimer\u27s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 1

High level soluble expression, one-step purification and characterization of HIV-1 p24 protein

<p>Abstract</p> <p>Background</p> <p>P24 protein is the major core protein of HIV virus particle and has been suggested as a specific target for antiviral strategies. Recombinant p24 protein with natural antigenic activity would be useful for various studies, such as diagnostic reagents and multi-component HIV vaccine development. The aim of this study was to express and purify the p24 protein in soluble form in <it>E.coli</it>.</p> <p>Results</p> <p>According to the sequence of the p24 gene, a pair of primers was designed, and the target sequence of 700 bp was amplified using PCR. The PCR product was cloned into pQE30 vector, generating the recombinant plasmid pQE30-p24. SDS-PAGE analysis showed that the His-tagged recombinant p24 protein was highly expressed in soluble form after induction in <it>E. coli </it>strain BL21. The recombinant protein was purified by nickel affinity chromatography and used to react with HIV infected sera. The results showed that the recombinant p24 protein could specifically react with the HIV infected sera. To study the immunogenicity of this soluble recombinant p24 protein, it was used to immunize mice for the preparation of polyclonal antibody. Subsequent ELISA and Western-Blot analysis demonstrated that the p24 protein had proper immunogenicity in inducing mice to produce HIV p24 specific antibodies.</p> <p>Conclusion</p> <p>In this work, we report the high level soluble expression of HIV-1 p24 protein in <it>E. coli</it>. This soluble recombinant p24 protein specifically react with HIV infected sera and elicit HIV p24 specific antibodies in mice, indicating this soluble recombinant p24 protein could be a promising reagent for HIV diagnosis.</p

A pilot study on acute inflammation and cancer: a new balance between IFN-γ and TGF-β in melanoma

Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little development on cases where inflammation on or near a wound and a tumor exist simultaneously. Therefore, this pilot study aims to observe the impact of a wound on a tumor, to build a new mouse tumor model with a manufactured surgical wound representing acute inflammation, and to evaluate the relationship between acute inflammation or wound healing and the process of tumor growth. We focus on the two phases that are present when acute inflammation influences tumor. In the early phase, inhibitory effects are present. The process that produces these effects is the functional reaction of IFN-γ secretions from a wound inflammation. In the latter phase, the inhibited tumor is made resistant to IFN-γ through the release of TGF-β to balance the inflammatory factor effect on the tumor cells. A pair of cytokines IFN-γ/TGF-β established a new balance to protect the tumor from the interference effect of the inflammation. The tumor was made resistant to IFN-γ through the release of TGF-β to balance the inflammatory effect on the tumor cells. This balance mechanism that occurred in the tumor cells increased proliferation and invasion. In vitro and in vivo experiments have confirmed a new view of clinical surgery that will provide more detailed information on the evaluation of tumors after surgery. This study also provides a better understanding of the relationship between tumor and inflammation, as well as tumor cell attacks on inflammatory factors

Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model

AIM: To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis. METHODS: A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls (HC), ulcerative colitis model group (UC), UC with 7 d of moxibustion (UC-7), UC with 14 d of moxibustion (UC-14), UC with mesalazine gavage (UC-W), HC with 7 d of moxibustion (HC-7), HC with 14 d of moxibustion (HC-14). Moxibustion was applied to the bilateral Tianshu (ST25). Gut microbiome profiling was conducted by 16S rRNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS: Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term (7 d) but no longer term (14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12 (IL-12) (P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, IgA, tumour necrosis factor-α and its receptors 1 (TNFR1) and TNFR2 (P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10 (P < 0.01) and transforming growth factor-β (P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion. CONCLUSION: Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity

Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer\u27s disease.

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer\u27s disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD-C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid-β1-42 (Aβ 1-42 ), Tau protein phosphorylation (P-tau) and β-site APP-cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD-C10 administration boosted the expression of synapse-associated proteins, such as postynaptic density protein 95, synaptophsin, α-amino 3-hydroxy-5-methyl-4-isoxa-zolep-propionate receptor and neurotrophic factors, e,g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Taken together, our results demonstrate that FSD-C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ 1-42 and P-tau, and promoting the generation of synapse-associated proteins and neurotrophic factors