The roots and rhizomes of
have neuroprotection and cardiovascular protection effects. However, the specific mechanism of
is not yet clear. Nardochinoid C (DC) is a new compound with new skeleton ...isolated from
and this study for the first time explored the anti-inflammatory and anti-oxidant effect of DC. The results showed that DC significantly reduced the release of nitric oxide (NO) and prostaglandin E
(PGE
) in lipopolysaccharide (LPS)-activated RAW264.7 cells. The expression of pro-inflammatory proteins including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also obviously inhibited by DC in LPS-activated RAW264.7 cells. Besides, the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also remarkably inhibited by DC in LPS-activated RAW264.7 cells. DC also suppressed inflammation indicators including COX-2, PGE
, TNF-α, and IL-6 in LPS-stimulated THP-1 macrophages. Furthermore, DC inhibited the macrophage M1 phenotype and the production of reactive oxygen species (ROS) in LPS-activated RAW264.7 cells. Mechanism studies showed that DC mainly activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme oxygenase-1 (HO-1) and thus produced the anti-inflammatory and anti-oxidant effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings suggested that DC could be a new Nrf2 activator for the treatment and prevention of diseases related to inflammation and oxidative stress.
Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses ...triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC.
In this article, we study the output regulation of an unstable heat equation with recycle, where the right boundary heat flux is fed back to the other end through a recycle loop, and the reference ...signal and the disturbances in all channels are generated by an exosystem with known frequencies. By designing a static feedback with the noncollocated observation and choosing the proper control gain, we stabilize the heat system without disturbances. Then we solve the regulator equation and construct an observer based on the tracking error to obtain the robust output feedback regulator. The closed-loop system is proved to be well-posed and uniformly bounded, and the regulated output tracks the reference signal exponentially. The numerical simulations are carried out to demonstrate the effectiveness of the proposed control.
Nardochinoid B (NAB) is a new compound isolated from
. Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 ...cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.
Salvia miltiorrhiza is a model plant for Chinese herbal medicine with significant pharmacologic effects due to its tanshinone components. Our previous study indicated that nitrogen starvation stress ...increased its tanshinone content. However, the molecular mechanism of this low nitrogen-induced tanshinone biosynthesis is still unclear. Thus, this study aimed to elucidate the molecular mechanism of tanshinone biosynthesis in S. miltiorrhiza under different N conditions N-free (N0), low-N (Nl), and full-N (Nf, as control) conditions by using transcriptome and metabolome analyses. Our results showed 3,437 and 2,274 differentially expressed unigenes between N0 and Nf as well as Nl and Nf root samples, respectively. N starvation (N0 and Nl) promoted the expression of the genes involved in the MVA and MEP pathway of tanshinone and terpenoid backbone biosynthesis. Gene ontology and KEGG analyses revealed that terpenoid backbone biosynthesis, hormone signal transduction, and phenylpropanoid biosynthesis were promoted under N starvation conditions, whereas starch and sucrose metabolisms, nitrogen and phosphorus metabolisms, as well as membrane development were inhibited. Furthermore, metabolome analysis showed that metabolite compounds and biosynthesis of secondary metabolites were upregulated. This study provided a novel insight into the molecular mechanisms of tanshinone production in S. miltiorrhiza in response to nitrogen stress.
Display omitted
Inflammatory bowel disease (IBD), majorly include Crohn’s disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, ...which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg−1) and the positive drug Sulfasalazine (SASP, 200 mg kg−1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.
We propose a perfect absorber of dual-band, high sensitivity and angle-insensitive based on surface plasmon polaritons (SPP) in monolayer graphene. The structure is composed of the metamaterial and ...graphene with stable performance. The absorption properties of the structure are theoretically investigated by simulation. Perfect absorption is achieved in the laser band range of 10.6 μm and the mid-infrared range of 7.54 μm. At the same time, the absorption peaks can be tuned by adjusting the structural parameters and the Fermi energy level of the graphene. In the simulation, the absorption performance of this structure is insensitive to angles, where both of the absorption peaks remain 95 % in the incident angle range of 0– 50°. Moreover, the refractive index sensitivity of M1 and M2 can reach 3000 nm/RIU and 2000 nm/RIU, respectively. This research provides an effective solution for the development of mid-infrared optical devices and compatible camouflage application based on graphene.
Display omitted
Summary
Objective
Vigabatrin (VGB) is the first‐line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin‐associated brain abnormalities on magnetic ...resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion‐weighted imaging (DWI) and T2‐weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB.
Methods
Children with IS receiving VGB were selected as the study subjects. Whether VABAM occurred or not was categorized as the VABAM group and the non‐VABAM group, respectively. Their general clinical data and medication exposure were collected. The possible risk factors of VABAM and different MRI sequences were compared and statistically analyzed.
Results
A total of 77 children with IS were enrolled in the study, of which 25 (32.5%) developed VABAM. Twenty‐three of the 25 VABAM cases have a peak dosage of VGB between 50 and 150 mg/kg/day. The earliest observation time of VABAM was 30 days. Regression analysis of relevant risk factors showed that the peak dosage of VGB was the risk factor for VABAM. Comparison between different MRI sequences showed that DWI is more sensitive than T2WI to the evaluation of VABAM.
Significance
In our study, the occurrence of VABAM was 32.5%, indicating a higher incidence than in most previous reports. In addition, we once again verified that the peak dosage of VGB was the risk factor of VABAM. Caution should be exercised that our data also suggest that VABAM may occur even using the conventional dosage of VGB (ie, 50–150 mg/kg/day). Therefore, even when using the conventional dosage of VGB, regular MRI examination should be required. Furthermore, DWI sequence should be used as a routine examination sequence when MRI is performed in children with IS who are receiving VGB.
Both human telomere and proto-oncogene c-MYC can form G-quadruplex (G4) with various conformations. Porphyrin derivative (TMPyP4) could stabilize G4, and thus is considered as a potential drug for ...anticancer therapeutics. In this paper, the translocation behaviors of three typical G4s (telomere basket, telomere hybrid-1 and c-MYC Pu22 parallel) and their interaction with TMPyP4 were investigated with a single protein nanopore sensing interface with the same main electrolyte of 0.5 M tetramethylammonium chloride. As observed by the statistics of the dwell time of the current pulses, in the presence of K+, the parallel G4 is more stable than the hybrid-1 G4, while the basket G4 in the presence of Na+ exhibited shortest duration. The dwell time of all of the G4s increased as the result of interaction with TMPyP4, indicating an obvious stabilizing effect. This study demonstrated that the single nanopore sensing interface not only reveal the stability of various G4 conformations at a single-molecule level, but also provide the interaction information of a ligand, which could be useful in the drug design.
Display omitted
•The translocation behaviors of three G4s G4 were examined, and compared for the first time with nanopore sensing interface.•Interaction of porphyrin derivative TMPyP4 with G4s was investigated and compared with the proposed method.•This work provides a new method for obtaining knowledge about the stability of G4 itself and its interaction with ligand.
Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of ...pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.
•Pogostone inhibited the wrinkle formation and skin laxity mainly by repairing collagen and elastic fibers.•Pogostone prevented UV-induced skin photoaging through inhibiting oxidative stress and inflammation responses.•Pogostone could down-regulate the levels of MMP-1 and MMP-3 in UV-irradiated mice.•Pogostone is regarded as a feasible candidate agent for anti-photoaging cosmetics.
PDF
