HnRNP A2/B1 as a potential anti-tumor target for triptolide based on a simplified thermal proteome profiling method using XGBoost.

BACKGROUND: Triptolide (TP) is a highly active natural medicinal ingredient with significant potential in anticancer. The strong cytotoxicity of this compound suggests that it may have a wide range of targets within cells. However, further target screening is required at this stage. Traditional drug target screening methods can be significantly optimized using artificial intelligence (AI). PURPOSE:  This study aimed to identify the direct protein targets and explain the multitarget action mechanism of the anti-tumor effect of TP with the help of AI. METHODS:  The CCK8, scratch test, and flow cytometry analysis were used to examine cell proliferation, migration, cell cycle, and apoptosis in tumor cells treated with TP in vitro. The anti-tumor effect of TP in vivo was evaluated by constructing a tumor model in nude mice. Furthermore, we established a simplified thermal proteome analysis (TPP) method based on XGBoost (X-TPP) to rapidly screen the direct targets of TP. RESULTS: We validated the effects of TP on protein targets through RNA immunoprecipitation and pathways by qPCR and Western blotting. TP significantly inhibited tumor cell proliferation and migration and promoted apoptosis in vitro. Continuous administration of TP to tumor mice can significantly suppress tumor tissue size. We verified that TP can affect the thermal stability of HnRNP A2/B1 and exert anti-tumor effects by inhibiting HnRNP A2/B1-PI3K-AKT pathway. Adding siRNA to silence HnRNP A2/B1 also significantly down-regulated expression of AKT and PI3K. CONCLUSION: The X-TPP method was used to show that TP regulates tumor cell activity through its potential interaction with HnRNP A2/B1.

Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines.@*METHODS@#A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared.@*RESULTS@#After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05).@*CONCLUSION@#Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.

Chitosan Hydrogel Supplemented with Metformin Promotes Neuron-like Cell Differentiation of Gingival Mesenchymal Stem Cells.

Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem-cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/ß-glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and ß-Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem-cell neural regeneration.

Magnetic resonance spectroscopy features of the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the changes in biochemical metabolites in the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder (ASD).@*METHODS@#In this prospective study, magnetic resonance spectroscopy (MRS) with point-resolved spatial selection was used to analyze the thalamus and the cerebellum at both sides in 50 children with ASD aged 2-6 years. Creatine (Cr) was as the internal standard to measure the relative values of N-acetylaspartate (NAA)/Cr, choline (Cho)/Cr, myoinositol (MI)/Cr, and glutamine and glutamate complex (Glx)/Cr, and the differences in metabolites and their association with clinical symptoms were compared.@*RESULTS@#In the children with ASD, NAA/Cr in the left thalamus was positively correlated with the scores of hearing-language and hand-eye coordination in the Griffiths Development Scales-Chinese (@*CONCLUSIONS@#There are metabolic disorders in the cerebellum and the thalamus in children with ASD, and there is a correlation between the changes of metabolites in the left cerebellum and the left thalamus. Some metabolic indexes are related to the clinical symptoms of ASD. MRS may reveal the pathological basis of ASD and provide a basis for diagnosis and prognosis assessment of ASD as a noninvasive and quantitative detection method.

Clinical effect and mechanism of / 中国针灸

OBJECTIVE@#To observe the effect of @*METHODS@#A total of 60 children with intellectual disability were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off). In the control group, rehabilitation training and routine acupuncture were adopted, 30 min each time, once a day, 6 times a week for 3 months. On the base of the treatment as the control group, @*RESULTS@#Compared before treatment, the scores of DQ and ADL and the serum levels of DA, NE, 5-HT after treatment were increased (@*CONCLUSION@#On the base of rehabilitation training and routine acupuncture,

Compost supplementation with nitrogen loss and greenhouse gas emissions during pig manure composting.

This research investigated the influence of biochar (B) and bean dregs (BD) amendments on carbon and nitrogen losses through greenhouse gas (GHG) emissions during pig manure (PM) composting. The treatments included 15% BD, 10% B and 15% BD+10% B (w/w dry basis of PM) amendments in the compost, whereas the CK (control) lacked any additives. The NH4+-N, C/N and germination index (GI) of the end products ensured compost maturity. Compared with the CK, the 15% BD amendment increased the total nitrogen content (TKN) of the final product by 8.05% but also increased NH3 (54.98%) and GHG emissions (40.35%) as well as nitrogen loss (25.62%). Furthermore, the combined treatment of 15% BD+10% B improved the TKN (2.83%) of the end product and controlled NH3 emissions (33.71%), GHG emissions (29.56%) and nitrogen loss (24.26%) while increasing CO2 only with the 15% BD amendment. Therefore, the combination of BD+B was recommended.

Comparison of three herbal proparations in airway remodeling in rats with chronic asthmatic / 中成药

AIM To research the antiasthmatic effects of Zuogui Pills,Yougui Pills and Yupingfeng Powder and their mechanism of action.METHODS Male Brown Norway rats were randomly divided into five groups.OVA was used to induce the model of chronic asthma.Five groups of asthmatic rats were given Zuogui Pills,Yougui Pills,Yupingfeng Powder by gavage once daily for 14 d,respectively.The normal and the model group were given normal saline.Penh value,serum Thl,Th2 inflammatory cytokines,and CROT and ACTH protein levels were determined.Pathological changes of airway remodeling were measured.RT-PCR method was used to measure the expression of CRH mRNA in hypothalamus,and TGF-β1 and Smad3 mRNA in lung tissues.RESULTS Penh values of Yupingfeng Powder group and Yougui Pills group were significantly lower than that of Zuogui Pills group.The Thl inflammatory cytokine of Yupingfeng Powder group was significantly higher than that of Zuogui Pills group,while the Th2 cytokine was significantly lower than that of Zuogui Pills group.In Yougui Pills group,only IL-5 was significantly lower than that of Zuogui Pills group.Serum CROT,ACTH protein and CRH mRNA of Yupingfeng Powder group were significantly higher than those in Zuogui Pills group.No significant difference was found between Yupingfeng Powder group and Zuogui Pills group with regard to TGF-β1 and Smad3 mRNA.Smad3 mRNA of Yougui Pills group was significantly higher than that of the model group.Airway remodeling was significantly reduced by Yupingfeng Powder and Zuogui Pills.The number of goblet cells in Yougui Pills group was significantly lower than that in Zuogui Pills group.CONCLUSION All the three formulaes possess significant antiasthma effects.Regulation effects of Yupingfeng Powder on Thl/Th2 balance,HPA and TGF-β1/Smad3 pathway are strong.Compared with Zuogui Pills,Yougui Pills possesses weaker TGF-β1/Smad3 regulative effects and stronger HPA regulative effects.

Curcumin inhibits the replication of enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.

[Monitoring models for phosphorus content of apple flowers based on hyperspectrum].

By using ASD FieldSpec 3 field spectrometer, the hyperspectral reflectance of apple flowers at full-blooming stage was measured under laboratory conditions, and the correlations of the hyperspectral reflectance with the phosphorus content of apple flowers were analyzed based on the original spectrum and the first derivative spectral characteristics of the flowers. The sensitive wavebands were determined, the characteristic spectral parameters were constructed, and the monitoring models for the phosphorus content of apple flowers were established accordingly. Correlation analysis showed that the phosphorus content of apple flowers was significantly positively correlated with the original spectral reflectance at 350-370 nm, 670-1385 nm, and 1620-1760 nm, and the first derivative reflectance at 500-520 nm, and significantly negatively correlated with the first derivative reflectance at 670-730 nm. The spectral parameters DVI (936, 676), DVI (977, 676), NDVI (936, 676) and NDVI (977, 676) had close correlations with the phosphorus content of apple flowers, the correlation coefficients being all > 0.77. By using these spectral parameters as independent variables, four monitoring models for the phosphorus content of apple flowers were established, among which, the model with NDVI (936, 676) as the variable was validated as the best monitoring model, its determination coefficient was the highest (R2 = 0.9385), root mean square error and relative error were the smallest (RMSE = 0.6883, and RE = 7.6%), and prediction accuracy reached 92.4%.