Search

The implementation of targeted therapies for breast cancer has been a challenge. Saikosaponin D (SsD), a triterpene saponin derived from Bupleurum, exhibits potential therapeutic properties for cancer therapy. Here, the role of SsD in broad antiproliferation effects in breast cancer was investigated, and the SsD pharmaceutical efficacy was evaluated by metabolomics analysis. Low (0.4 mg/kg) and high (2.0 mg/kg) concentrations of SsDs were used to treat breast cancer tumors in mice by intraperitoneal injection. Blood samples of mice were collected and the serum samples were extracted after SsD administration for different days. Subsequently, the serum samples were analyzed by ultra-high performance liquid chromatography tandem Orbitrap mass spectrometry (UPLC-Orbitrap MS). According to the “80% rule”, UPLC-Orbitrap MS data were processed and proper ions were screened out for further analysis. Statistical methods including one-way analysis of variance (One-way ANOVA), principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to cross validate the reasonable and accuracy of the models. Representational metabolite ions present significant differences acquired by comparison within/between control group, SsD low concentration group and SsD high concentration group. The results of animal survival experiments demonstrated that SsD had obvious therapeutic effect on tumor. Mice treated with low and high concentrations of SsD showed 60% and 80% survival rate, respectively, with a significant increase in survival compared to untreated control mice. Metabonomic results showed that 12 target metabolite ions including pipecolic acid, N-acryloylglycine, 3-methyleneindolenine, L-kynurenine, phenylethylamine, DL-2-aminooctanoic acid, N (6)-methyllysine, indoleacetaldehyde, 3-methylhistamine, hexanoylglycine, hypoxanthine and hexanoylcarnitine were obtained by intra-group (in control group) screening. The signal intensities of these 12 ions changed significantly in the process of tumor growth, which provided theoretical basis for the study of tumor development and evolution. Meanwhile, 7 important metabolite ions including 3-methylene-indolenine, phenylethylamine, pipecolic acid, L-kynurenine, indoleacetaldehyde, 5-acetylamino-6-formylamino-3-methyluracil and proline betaine were obtained by analyzing inter-group data (compared among three groups), and the first 5 metabolite ions were overlapped with the ions in the list of intra-group screening. Moreover, the biological significances of the selected ions with significant difference were investigated, and two highly correlated manifested metabolic pathways including amino acid metabolism and nucleotide metabolism were discussed. Overall, the results derived from intra-group metabolomic analysis were highly correlated with the inter-group results, and the metabolites along the relevant pathways deserve further attention. This study provides a practical strategy for targeting metabolic analysis using natural product to improve the survival of patients with breast cancer.

Objective To investigate the psychological and behavioral problems and related influencing factors in children and adolescents during the coronavirus disease 2019 (COVID-19) epidemic. Methods China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science were searched using the method of subject search for articles published up to March 31, 2022, and related data were extracted for Scoping review. Results A total of 3 951 articles were retrieved, and 35 articles from 12 countries were finally included. Most of the articles were from the journals related to pediatrics, psychiatry, psychology, and epidemiology, and cross-sectional survey was the most commonly used research method. Psychological and behavioral problems in children and adolescents mainly included depression/anxiety/stress, sleep disorder, internet behavior problems, traumatic stress disorder, and self-injury/suicide. Influencing factors were analyzed from the three aspects of socio-demographic characteristics, changes in living habits, and ways of coping with COVID-19. Conclusions During the COVID-19 epidemic, the psychological and behavioral problems of children and adolescents in China and overseas are severe. In the future, further investigation and research can be carried out based on relevant influencing factors to improve the psychological and behavioral problems. [ABSTRACT FROM AUTHOR]

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC 50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

Objectives: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1)., Methods: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L 4 to L 6 , stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L 4 to L 6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected., Results: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group ( P< 0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group ( P <0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group ( P< 0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group ( P< 0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group ( P< 0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group ( P< 0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group ( P <0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group ( P< 0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group ( P< 0.05)., Conclusions: Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.

Objectives: To investigate the psychological and behavioral problems and related influencing factors in children and adolescents during the coronavirus disease 2019 (COVID-19) epidemic., Methods: China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science were searched using the method of subject search for articles published up to March 31, 2022, and related data were extracted for Scoping review., Results: A total of 3 951 articles were retrieved, and 35 articles from 12 countries were finally included. Most of the articles were from the journals related to pediatrics, psychiatry, psychology, and epidemiology, and cross-sectional survey was the most commonly used research method. Psychological and behavioral problems in children and adolescents mainly included depression/anxiety/stress, sleep disorder, internet behavior problems, traumatic stress disorder, and self-injury/suicide. Influencing factors were analyzed from the three aspects of socio-demographic characteristics, changes in living habits, and ways of coping with COVID-19., Conclusions: During the COVID-19 epidemic, the psychological and behavioral problems of children and adolescents in China and overseas are severe. In the future, further investigation and research can be carried out based on relevant influencing factors to improve the psychological and behavioral problems.

Human activity is the main driving force of the change of land cover and landscape patterns. However, there are few studies focusing on the mechanism of human-induced change of land cover and landscape patterns at village scale. In this study, taking low-slope hilly area of Dali City, Northwestern Yunnan Province as a case study area, high resolution satellite images were introduced to find out the rules of land cover and landscape pattern changes, i.e. GeoEye-1 of 2009 and World- View-3 of 2014. The object-oriented and human-computer-interaction approaches were applied to interpret the images using ArcGIS 10.2 and ENVI 5.2. The results showed that, the main land cover types in the study area were forest land, paddy field and dry land in 2009, with forest, bulldozed unbuilt ground and paddy field in 2014, accounting for 82.8% and 70.9% of the total area, respectively. The land cover transition showed that, during 2009-2014, the main land cover change flows were from forest land, paddy field and dry land, to bulldozed unbuilt ground and construction land. Furthermore, the area of bulldozed but unbuilt land had increased to be 531.57 hm² in 2014, which mainly came from forest land (42.8%), dry land (21.7%), and paddy field (14.2%). Landscape pattern change was characterized as the increase of patch quantity and density, the decrease of mean patch size, the complication of patch shape, the fragmentation of landscape patches, and the diversification of landscape patterns.

This study is to investigate the effect of Euphorbia humifusa effective fraction (EHEF) on the CYP51 enzyme activity, the lanosterol content and the MEP, SUB gene expression of Trichophyton rubrum. Trichophyton rubrum was treated by EHEF for 7 days at 26 degrees C. The activity of CYP51 enzyme of Trichophyton rubrum in the cell membrane was determined by using ELISA kit, and the lanosterol content was investigated by using high performance liquid chromatography (HPLC), and the MEP, SUB gene expression of Trichophyton rubrum was detected with the reverse transcription polymerase chain reaction (RT-PCR) method. Results showed that EHEF can decrease the membrane CYP51 enzyme activity, and it also can accumulate the fungal lanosterol in a dose-dependent manner, and it also can decrease the gene expression of MEP and SUB. The antifungal mechanism of EHEF may be related to the inhibition on CYP51 enzyme activity, and to the effects on fungal cell membrane ergosterol biosynthesis. It may also play an antifungal effect by inhibiting the MEP, SUB gene expression of fungal proteases.