Chemical profile and difference analysis of four parts of Strobilanthes sarcorrhiza by ultrafast flow liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and multivariate statistical analysis.

Strobilanthes sarcorrhiza (CTS) is a medicinal plant with various pharmacological effects such as tonifying kidney and anti-inflammatory. However, the chemical composition and difference of its four parts (leaves, stems, rhizomes, and root tubers) have been rarely reported. In this study, ultrafast flow liquid chromatography coupled with quadrupole-time-of-flight MS was applied to analyze the chemical profile of CTS and identify 55 compounds, including terpenoids, phenylethanol glycosides, fatty acid derivatives, chain glycosides, flavonoid glycosides, and others. Among these compounds, 34 compounds were first identified in CTS. They were mainly terpenoids, phenylethanol glycosides, fatty acid derivatives, and so forth. Multivariate statistical analysis, such as principal component analysis and orthogonal partial least squares-discriminant analysis were also used to evaluate the difference in chemical compounds from the four parts of CTS. The results showed that phenylethanol glycosides were the main compounds of the underground parts, while terpenoids were the main compounds of the aboveground parts. This study revealed the chemical diversity and similarity of CTS and suggested that the rhizomes could be used as an alternative medicinal part to improve the resource utilization of CTS.

Dietary niacin affects intestinal morphology and functions via modulating cell proliferation in weaned piglets.

Niacin deficiency leads to inflammation of mucous membranes and diarrhoea. There are few reports on the effects of niacin on the intestinal health of weaned piglets. The present study was conducted to analyse the effects of niacin in weaned piglets along with its underlying mechanism. A total of 48 25-day-old weaned piglets (24 females and 24 males) were randomly allotted into four groups, each treatment were supplemented with 22.5, 30, 45, and 75 mg kg-1 niacin for a period of 14 days, with 12 piglets per diet and 1 piglet per pen. Six piglets (3 males and 3 females) were randomly selected from each treatment group and euthanised for intestinal tissue sampling on days 7 and 14 after the weaning day (day 0), respectively. Dietary niacin did not affect the growth performance of weaned piglets but quadratically affected (P < 0.05) the diarrhoea rate from days 7 to 14. The duodenal villus height and width and crypt depth in the 30 mg kg-1 niacin group were greater than those in the 45 mg kg-1 niacin group on day 7, and the jejunal crypt depth, ileal crypt depth, villus height and villus width decreased (linear, P < 0.05) with the increase in dietary niacin. However, the dietary supplementation with niacin increased (linear, P < 0.001) the jejunal villus height, crypt depth and villus width on day 14. Dietary niacin increased (linear, P < 0.05) the alkaline phosphatase activity in the jejunal mucosa of weaned piglets on day 7 but decreased (linear, P < 0.05) its activity on day 14. The number of Ki67 positive cells per crypt was decreased (linear, P < 0.05) with the dietary niacin on day 7 but increased (linear, P < 0.05) with dietary niacin contents on day 14. Moreover, dietary niacin altered (P < 0.05) SLC5A1, SLC15A1, SLC6A19, TJP-1, occludin and claudin-1 mRNA expression in the small intestine. These results indicate that dietary niacin has different effects on intestinal morphology and functions in the first and second weeks postweaning and that the dietary supplementation with niacin may, by modulating intestinal cell proliferation, affect the intestinal health.

Effects of varying dietary folic acid during weaning stress of piglets.

The present study was conducted to evaluate the effect of dietary folic acid on the growth performance, intestinal morphology, and intestinal epithelial cells renewal in post-weaning piglets. Twenty-eight piglets (weaned at day 21, initial body weight of 6.73 ± 0.62 kg) were randomly allotted to 4 treatments with 7 pens per diet and 1 piglet per pen. The piglets were fed the same antibiotic-free and zinc oxide-free basal diets supplemented with folic acid at 0, 3, 9, and 18 mg/kg for 14 days. The results showed that dietary supplementation with folic acid increased villus height (VH) (P = 0.003; linear, P = 0.001), VH-to-crypt depth (VH:CD) ratio (P = 0.002; linear, P = 0.001), villus surface area (VSA) (P = 0.026; linear, P = 0.010). The analyzed parameters ADG, serum urea nitrogen (BUN) content, VH, VSA, and serum folate (SF) concentration responded linearly to the dietary folic acid concentration when the dietary folic acid concentration was below 4.42, 5.26, 4.79, 3.47, and 3.53 mg/kg respectively (R 2  = 0.995, 0.995, 0.999, 0.999, 0.872, P = 0.09, 0.07, 0.09, 0.09, 0.36, respectively), as assessed by a two-linear broken-line regression. Above these breakpoints, the response of ADG, VH, VSA, and SF plateaued in response to changes in dietary folic acid concentration. Moreover, dietary supplementation with folic acid significantly increased the lactase (P = 0.001; linear, P = 0.001) and sucrase activities (P = 0.021; linear, P = 0.010) in the jejunal mucosa of weaned piglets. The mRNA expression of solute carrier family 6 member 19 (SLC6a19), solute carrier family 1 member 1 (SLC7a1), tumor necrosis factor-α (TNF-α), the number of Ki67 positive cells, and cell shedding rate had a significant linear contrast (P = 0.023, 0.021, 0.038, 0.049, and 0.008, respectively) in dietary folic acid groups. In conclusion, our results indicate that folic acid supplementation can improve the growth performance and intestinal morphology of weaned piglets by maintaining the balance of epithelial cell renewal.

Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factors.

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1ß, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/ß2-glycoprotein I (oxLDL/ß2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr -/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1ß) and hepatic (TNF-α, IL-1α, IL-1ß) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.

Current Advances and Limitations of Deep Learning in Anticancer Drug Sensitivity Prediction.

Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a branch of machine learning, is an important aspect of in silico research. Its outstanding computational performance means that it has been used for many biomedical purposes, such as medical image interpretation, biological sequence analysis, and drug discovery. Several studies have predicted anticancer drug sensitivity based on deep learning algorithms. The field of deep learning has made progress regarding model performance and multi-omics data integration. However, deep learning is limited by the number of studies performed and data sources available, so it is not perfect as a pre-clinical approach for use in the anticancer drug screening process. Improving the performance of deep learning models is a pressing issue for researchers. In this review, we introduce the research of anticancer drug sensitivity prediction and the use of deep learning in this research area. To provide a reference for future research, we also review some common data sources and machine learning methods. Lastly, we discuss the advantages and disadvantages of deep learning, as well as the limitations and future perspectives regarding this approach.

[Analysis of differential genes related to dormancy release of Paris polyphylla var. chinensis seeds by transcriptome sequencing].

The study aims at exploring the expression of differential genes and related metabolic pathways in the process of seed dormancy release. The dormant embryo and the dormant released embryo of Paris polyphylla var. chinensis were used as the test materials, a new generation high-throughput sequencing methods to sequence the transcriptome of the samples was used to carry out systematic bioinformatics analysis. We obtained 62 882 650 and 62 263 366 clean reads from the DNA libraries of the samples before and after dormancy breaking. A total of 69 248 differentially expressed genes(DEGs) were obtained, 56 426 up-regulated genes and 12 822 down-regulated genes. There are 138 267 differentially expressed genes in the process of embryo dormancy release, which were annotated by GO function to 58 subclasses of biological processes, molecular functions and cell components. The annotated differentially expressed genes were closely related to metabolic processes, biological regulation, cell component synthesis and enzyme catalytic activity. We found 139 metabolic pathways through pathway analysis of 58 722 differentially expressed genes. Before and after dormancy, DEGs were mainly enriched in carbon metabolism, secondary metabolite biosynthesis and polysaccharide metabolism. Based on the annotation results in KEGG database, we found 16 metabolic pathways related to the dormancy release of P. polyhoylla var. chinensis. A large number of differentially expressed genes were involved in embryo morphogenesis, polysaccharide decomposition and protein synthesis during seed development and dormancy release. It involves the interaction of multiple metabolic pathways and constitutes a complex regulation network for dormancy relief.

Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy.

Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently in hematopoietic malignancy, but rarely in solid tumors which instead commonly have reduced activity. The impact of decreased TET activity in solid tumors is not known. Here we show that TET2 mediates interferon γ (IFNγ)-JAK-STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration and cancer immunity. IFNγ stimulated STAT1 to bind TET2 and recruit TET2 to hydroxymethylate chemokine and PD-L1 genes. Reduced TET activity was associated with decreased TH1-type chemokines and tumor-infiltrating lymphocytes (TILs) and the progression of human colon cancer. Deletion of Tet2 in murine melanoma and colon tumor cells reduced chemokine expression and TILs, enabling tumors to evade anti-tumor immunity and to resist anti-PD-L1 therapy. Conversely, stimulating TET activity by systematic injection of its co-factor, ascorbate/vitamin C, increased chemokine and TILs, leading to enhanced anti-tumor immunity and anti-PD-L1 efficacy and extended lifespan of tumor-bearing mice. These results suggest an IFNγ-JAK-STAT-TET signaling pathway that mediates tumor response to anti-PD-L1/PD-1 therapy and is frequently disrupted in solid tumors. Our findings also suggest TET activity as a biomarker for predicting the efficacy and patient response to anti-PD-1/PD-L1 therapy, and stimulating TET activity as an adjuvant immunotherapy of solid tumors.

Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes.

This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from a Sarawak local rice variety (local name: "BJLN") and a commercial rice variety, "MR219," on oxidative stress in rat H9c2(2-1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2), respectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were selected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dose-dependent cytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the dose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of induction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating these activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly upregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This preliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via upregulation in enzymatic activities and expression levels of CAT.

[Status and changes of soil nutrients in rhizosphere of Abelmoschus manihot different planting age].

Using soil chemical analysis method and combining with ICP-AES determination of mineral nutrition element content in rhizosphere soil of different planting age Abelmoschus Corolla Results show that along with the increase of planting age, the nitrogen (total N), available P and organic matter in rhizosphere soil of Abelmoschus Corolla content declined year by year and the soil got acidification. Heavy metal element content in agricultural land does not exceed national standards, but the content of element mercury (Hg) in rhizosphere soil of different planting age Abelmoschus Corolla declined. Request of microelement such as manganese (Mn) and zinc (Zn) had a increase tendency, but the content of magnesium (Mg) and sodium (Na) increased, and other nutrient elements had no changed rules or unchanged apparently. Consequently, exploring the change rules of different planting age Abelmoschus Corolla soil in rhizosphere as theoretical guidance of rational fertilization and subducting continuous cropping obstscles.

Inhibitory effects of ß,ß-dimethylacrylshikonin on hepatocellular carcinoma in vitro and in vivo.

ß,ß-Dimethylacrylshikonin is one of the most abundant naphthoquinones in the root extracts of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), which have been reported to have antitumor effects. This study evaluated the antiproliferative activity of ß,ß-dimethylacrylshikonin on human hepatocellular carcinoma (HCC) cells both in vitro and in vivo. In vitro, the MTT assay showed that ß,ß-dimethylacrylshikonin inhibited the proliferation of SMMC-7721 cells in both dose- and time-dependent manners with its 50% inhibitory concentration (IC(50) ) at 48 h being 15.01 ± 0.76 µg/mL. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and Hoechst staining detected the characteristics of cell apoptosis in ß,ß-dimethylacrylshikonin-treated cells and the apoptotic rates of treated groups were increased in a dose-dependent manner. Flow cytometric analysis revealed that ß,ß-dimethylacrylshikonin could block the cell cycle arrest at G2 phase. Furthermore, ß,ß-dimethylacrylshikonin down-regulated the mRNA and protein expression of Bcl-2 but up-regulated that of Bax. The cleaved caspase-3 protein was also detected in treated cells. The experiment in vivo showed that ß,ß-dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 determined by immunohistochemistry. The results indicate that ß,ß-dimethylacrylshikonin has significant antitumor effects on hepatocellular carcinoma both in vitro and in vivo.

Calycosin stimulates proliferation of estrogen receptor-positive human breast cancer cells through downregulation of Bax gene expression and upregulation of Bcl-2 gene expression at low concentrations.

BACKGROUND: Calycosin is one of main components in the herb radix astragali and is considered a typical phytoestrogen. It has either estrogenic or antiestrogenic effects that mainly depend on estrogen levels in vivo. This study investigated the effects and mechanisms of calycosin on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells in vitro. METHODS: ER-positive MCF-7 cells were treated with different concentrations of calycosin. Effects of calycosin on the proliferation of ER-positive MCF-7 cells were determined by the MTT assay. Apoptosis in these treated cells was examined by flow cytometry. The mRNA and protein levels of Bcl-2 and Bax in these treated cells were also determined by reverse-transcription polymerase chain reaction and immunohistochemical staining, respectively. RESULTS: Compared with the vehicle control, calycosin stimulated proliferation of ER-positive MCF-7 cells at low concentrations (2, 4, and 8 µmol/L). Furthermore, at these concentrations, calycosin decreased the percentage of early apoptosis in MCF-7 cells, downregulated mRNA and protein levels of Bax, and upregulated those of Bcl-2 at low concentrations. On the other hand, calycosin at higher concentrations (16 and 32 µmol/L) inhibited cell proliferation. CONCLUSION: At relatively low concentrations, calycosin has stimulatory effects on the proliferation of MCF-7 cells, with the estrogenic effect the mechanism.

[Mechanism of copper and zinc on tanshinones of cultivated Salvia miltiorrhiza].

OBJECTIVE: To study the mechanism of microelement including Cu and Zn on the accumulation of three danshinones in Salviae miltiorrhizae root and build a theory basis for its good quality and high yield. METHOD: Sand culture experiments were conducted to study the effect of Cu and Zn on the accumulation of three danshinones and oxidase including peroxidase and polyphenol oxidase activity in the plant root. The correlation between available Cu and Zn contents in matrix and oxidase activity in the plant root and, the correlation between available Cu and Zn contents in matrix and contents of tanshinones in the root were discussed. RESULT: Contents of danshinones in the root increased with the increasing of Cu and Zn concentration. Dynamic monitoring on contents of dan-shinones of the plant roots growing in the pots with different Cu and Zn concentration in the whole growing season showed that the contents of danshinones for 60 days were the lowest, for 120 days the highest and then dropped for 150 days. In addition, among available Cu and Zn contents of matrix, oxidase including peroxidase and polyphenol oxidase activity and contents of tanshinones in the root,the correlation between two factors were significant difference (P < 0.05 or P < 0.01). CONCLUSION: The mechanism of Cu and Zn on the accumulation of danshinones may be that Cu and Zn improve the activity of peroxidase and polyphenol oxidase, which promote transformation of phenolic compounds to terpenes and therefore to increase contents of danshinones.

[Comparative study of Buyang Huanwu Decoction and the different combinations of its ingredients on neurogenesis following ischemic stroke in rats].

OBJECTIVE: To investigate the effect of Buyang Huanwu Decoction (BYHWD) and the different combinations of its ingredients on neurogenesis following ischemic stroke in rats. METHODS: The model rats of ischemic stroke was established by blocking cerebral media artery with electrocoagulation through craniectomy, and electric stimulation, given from 24 h after blocking, 2 h daily for 15 successive days. They were divided into four groups, Group A treated with saline, Group B treated with BYHWD, Group C treated with BYHWD but earthworm subtracted, and Group D treated with Danggui Buxue Decoction (DGBXD). The expression of 5-bromodeoxyuridine (BrdU) in cerebral tissue was determined by immunohistochemical method. RESULTS: Large amount of BrdU immunoreactive cells presented in the hippocampal region of rats in Group B and C, densely arranged, partial in cluster, with the figure significantly different to that in Group A (P < 0.01), and the amount in the ischemic side was significantly more than that in the opposite side (P < 0.05). While comparing between Group A and D, the amount of BrdU immunoreactive cells in the hippocampal region showed insignificant difference (P > 0.05). CONCLUSION: BYHWD has a effect in promoting neurogenesis better than DGBXD.

[Effects of Buyanghuanwu decoction on nerve proliferation in rats with sequelae of ischemic stroke].

OBJECTIVE: To examine the effect of Buyanghuanwu decoction (BYHWD) in inducing nerve proliferation in rats with sequelae of ischemic stroke. METHODS: A rat model of ischemic stroke sequelae was established by means of craniectomy in which the right common carotid artery was ligated with 4-0 silk thread followed by cauterization of the right middle cerebral artery. Programmed electric shock was administered 24 h after the onset of ischemic stroke for 2 h daily for 20 consecutive days. The rats in sham operation group were not subjected to ligation of the right common carotid artery or right middle cerebral artery occlusion. The rats in the treatment groups were given oral BYHWD for 15 consecutive days. All the rats received repeated intraperitoneal injections of the cell proliferation-specific marker 5-bromodeoxyuridine (BrdU), and the intake of BrdU in the cerebral tissues was determined by immunohistochemistry. RESULTS: The number of BrdU-immunoreactive cells in the cerebral tissues of BYHWD-treated rats was significantly greater than that in the untreated model group. CONCLUSION: BYHWD can promote nerve proliferation in rats with ischemic stroke sequelae.