Andrographolide inhibits the proliferation and migration of vascular smooth muscle cells via PI3K/AKT signaling pathway and amino acid metabolism to prevent intimal hyperplasia.

Andrographolide (AGP) exerts pharmacological effects when used for the treatment of cardiovascular disease, but the molecular mechanisms underlying its inhibitory effects on the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal hyperplasia (IH) are unknown. The proliferation and migration of VSMCs treated with AGP were examined using the CCK-8, flow cytometry, and wound healing assays. Expression levels of proteins related to cell proliferation and apoptosis were quantified. Multi-omics analysis with RNA-seq and metabolome was used to explore the potential molecular mechanism of AGP treatment. Additionally, an in vivo model was established through ligation of the left common carotid artery to identify the therapeutic potential of AGP in IH. Molecular docking and western blotting were performed to verify the mechanism discovered with multi-omics analysis. The results showed that AGP inhibited the proliferation and migration of cultured VSMCs in a dose-dependent manner and alleviated IH-related vascular stenosis. AGP significantly downregulated the protein levels of CDK1, CCND1, and BCL2 and upregulated the protein level of BAX. Gene expression profiles showed a total of 3,298 differentially expressed genes (DEGs) after AGP treatment, of which 1,709 DEGs had upregulated expression and 1,589 DEGs had downregulated expression. KEGG enrichment analysis highlighted the PI3K/AKT signaling pathway, verified with the detection of the activation of PI3K and AKT phosphorylation. Further GO enrichment combined with metabolomics analysis showed that AGP inhibition in cultured VSMCs involved the amino acid metabolic process, and the expression levels of the two key factors PRDM16 and EZH2, identified with PPI and docking analysis, were significantly inhibited by AGP treatment. In conclusion, our study showed that AGP inhibited VSMCs proliferation and migration by suppressing the PI3K/AKT signaling pathway and amino acid metabolism, which, in turn, improved IH.

DCTPP1, a reliable Q-biomarker for comprehensive evaluation of the quality of tripterygium glycoside tablets based on chemical references.

BACKGROUND: As first-line clinical drugs, tripterygium glycoside tablets (TGTs) often have inconsistent efficacy and toxic side effects, mainly due to inadequate quality control. Therefore, clinically relevant quality standards for TGTs are urgently required. PURPOSE: Based on chemical substances and considering pharmacological efficacy, we aimed to develop an effective quality evaluation method for TGTs. METHODS: Representative commercial samples of TGTs were collected from different manufacturers, and qualitative UHPLC/LTQ-Orbitrap-MS and quantitative UHPLC-MS/MS analysis methods were successfully applied to evaluate their quality similarities and differences based on their chemical properties. Then the anti-immunity, anti-inflammatory and antitumor activities of TGTs and related monomers were evaluated using Jurkat, RAW264.7, MIA PaCa-2, and PANC-1 as cellular models. Subsequently, we predicted and verified small molecule-DCTPP1 interactions via molecular docking using the established DCTPP1 enzymatic activity assay. Finally, we performed a gray relational analysis to evaluate the chemical characteristics and biological effects of TGTs produced by different manufacturers. RESULTS: We collected 24 batches of TGTs (D01-D24) from 5 manufacturers (Co. A, Co. B, Co. C, Co. D, Co. E) for quality evaluation. The chemical composition analysis revealed significant differences in the substance bases of the samples. The D02, D18-D20 samples from Co. B constituted a separate group that differed from other samples, mainly in their absence of diterpenoids and triterpenoids, including triptolide, triptophenolide, and triptonide. In vitro anti-immunity, antitumor and anti-inflammatory tests using the same TGT concentration revealed that, except for D02, D18-D20, the remaining 20 samples exhibited different degrees of anti-immunity, antitumor and anti-inflammatory activity. Our experiments verified that triptolide, triptophenolide, and triptonide were all DCTPP1 inhibitors, and that TGTs generally exhibited DCTPP1 enzyme inhibitory activity. Moreover, the inhibitory activity of D02, D18-D20 samples from Co. B was much lower than that of the other samples, with a nearly tenfold difference in IC50. Further comprehensive analysis revealed a high correlation between DCTPP1 enzyme inhibition activity and the anti-immunity and antitumor and anti-inflammatory activities of these samples. CONCLUSION: The established DCTPP1 enzymatic activity assay proved suitable for quantitative pharmacological and pharmaceutical analysis to complement the existing quality control system for TGTs and to evaluate their effectiveness.

TiO2-coated MoP/phosphorus doped carbon nanorods for ultralong-life sodium ion batteries with high capacity.

How to green synthesize and construct MoP anode electrode materials with advanced structures for sodium-ion batteries still faces great challenges. Herein, a TiO2-coated MoP/phosphorus doped carbon (MoP@TiO2/P-C) nanorod with a new structure is constructed using TiO2-coated Mo-MOF as the precursor through an in situ topological conversion technique. In the synthesis process, the traditional highly toxic PH3 phosphorus is avoided. TEM results reveal that TiO2 nanoparticles are distributed at the interface between the MoP core and the P-doped carbon shell, which breaks the density of the carbon layer and facilitates ion transport. The GITT results demonstrate the fact that the diffusion coefficient of sodium ions is remarkably improved by two orders of magnitude due to the presence of TiO2. Notably, TiO2 can effectively cushion volume expansion with an almost negligible rate of 13%, allowing cells to manifest a high discharge capacity of 419 mA h g-1 at 0.5 A g-1 current density and exceptional stability where the specific capacity remains constant for 10 000 cycles at a high density of 10 A g-1 (∼81 seconds for one charging). The results indicate that MoP@TiO2/P-C possesses promising capabilities as an anode substance for SIBs. This also establishes a foundation for future investigations and practical use of this material in the field.

A new strategy for osteoarthritis therapy: Inhibition of glycolysis.

Osteoarthritis (OA) is a common degenerative disease of the joints. It is primarily caused by age, obesity, mechanical damage, genetics, and other factors, leading to cartilage degradation, synovial inflammation, and subchondral sclerosis with osteophyte formation. Many recent studies have reported that glycolysis disorders are related lead to OA. There is a close relationship between glycolysis and OA. Because of their hypoxic environment, chondrocytes are highly dependent on glycolysis, their primary energy source for chondrocytes. Glycolysis plays a vital role in OA development. In this paper, we comprehensively summarized the abnormal expression of related glycolytic enzymes in OA, including Hexokinase 2 (HK2), Pyruvate kinase 2 (PKM2), Phosphofructokinase-2/fructose-2, 6-Bisphosphatase 3 (PFKFB3), lactate dehydrogenase A (LDHA), and discussed the potential application of glycolysis in treating OA. Finally, the natural products that can regulate the glycolytic pathway were summarized. Targeting glucose transporters and rate-limiting enzymes to glycolysis may play an essential role in treating OA.

Effect of neuromuscular electrical stimulation combined with swallowing rehabilitation training on the treatment efficacy and life quality of stroke patients with dysphagia.

PURPOSE: To explore the therapeutic efficacy of neuromuscular electrical stimulation (NMES) combined with swallowing rehabilitation training on the healing effect and quality of life of stroke patients with dysphagia. METHODS: The clinical data of 63 stroke patients admitted to the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed. The included patients were divided into two groups according to different treatment plans: an observation group (n=33) treated with NMES combined with swallowing rehabilitation training, and a control group (n=30) treated by swallowing rehabilitation training alone. Before and after 2 courses of treatment, the Water swallow test, Functional Oral Intake Scale (FOIS), and MD Anderson Dysphagia Inventory (MDADI) were used to assess the swallowing function of patients in the two groups, and the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate patients' neurological deficit; the SA7550 surface electromyogram (EMG) analysis system was applied to collect surface EMG, and the F113-5 medical X-ray TV system was used to detect the mobility of the hyoid-throat complex; the negative emotions of patients were assessed using the Hamilton Rating Scale for Depression (HAMD) before and after treatment, and the quality of life was evaluated by the Swallowing Quality of Life (SWAL-QOL) questionnaire; and the occurrence of adverse reactions during treatment was recorded and compared between the two groups. RESULTS: There was no significant difference in swallowing function, duration of swallowing, maximum amplitude value, and hyoid-throat complex mobility between the two groups before treatment (P>0.05), nor were there any differences in the scores of FOIS, MDADI, NIHSS, HAMD, and SWAL-QOL before treatment (P>0.05). After treatment, however, the above indicators of both groups were significantly improved (P<0.05), and the improvements were more significant in the observation group compared with the control group (P<0.05). Moreover, the incidence of adverse reactions in both groups were relatively low without significant difference between groups (P>0.05). CONCLUSION: NMES combined with swallowing rehabilitation training is effective in the treatment of swallowing dysfunction following stroke. It can effectively improve patients' swallowing function and quality of life, and relieve their negative emotions, with a high safety profile, which is worthy of clinical promotion.

[Screening of anti-lung cancer bioactive compounds from Curcuma longa by target cell extraction and UHPLC/LTQ Orbitrap MS].

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology.

The effectiveness of functional electrical stimulation based on a normal gait pattern on subjects with early stroke: a randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of four-channel FES based on a normal gait pattern on improving functional ability in subjects early after ischemic stroke. METHODS: Forty-five subjects were randomly assigned into a four-channel FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14). Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and at 3 months after the treatment had finished. The assessments included Fugl-Meyer Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified Barthel Index (MBI). RESULTS: All 3 groups demonstrated significant improvements in all outcome measurements from pre- to posttreatment and further gains at followup. The score of FMA and MBI improved significantly in the four-channel group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI, and FAC in the four-channel group were significantly higher than those of the placebo group. CONCLUSIONS: This study indicated that four-channel FES can improve motor function, balance, walking ability, and performance of activities of daily living in subjects with early ischemic stroke.