Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment / 中国中药杂志

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

Effect of Modified Xijiao Dihuang Decoction () on Intestinal Flora and Th17/Treg in Rats with Radiation Enteritis / 中国结合医学杂志

OBJECTIVE@#To observe the effect of Modified Xijiao Dihuang Decoction (, MXDD) on rats with radiation enteritis, and explore its action mechanism.@*METHODS@#Thirty female Sprague Dawley rats were divided into the control, model, dexamethasone (DXM), golden bifid (GB) and MXDD groups using random number table, 6 rats in each group. Except the control group, the other rats were developed into radiation enteritis model by exposing to a single @*RESULTS@#On day 1 to 3 after radiation, compared with the control group, the body weight in model group was decreased (P<0.05 or P<0.01). Compared with the model group, MXDD could alleviate weight loss and diarrhea caused by irradiation. At the phylum level, MXDD cause a significant increase in Firmicutes, and a decrease in Proteobacteria (P<0.05 or P<0.01). At the genus level, MXDD reduced the proportion of Escherichia Shigella (P<0.01). In addition, IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment (P<0.05). Besides, Firmicutes and Lactobacillus were positively correlated with FoxP3 (r=0.73, 0.79, respectively; P<0.01), negatively correlated with IL-17 (r=0.66, 0.64, respectively; P<0.01 or P<0.05) and ROR-γt (r0.73, 0.81, respectively; P<0.01). Proteobacteria and Escherichia Shigella both had positive correlation with IL-17 (r 0.77, 0.57, respectively; P<0.01 or P<0.05 ) and ROR-γt (r=0.94, 0.79, respectively; P<0.01) and negative correlation with FoxP3 (r0.74, 0.65; P<0.01).@*CONCLUSION@#MXDD could improve the survival status of irradiated rats by regulating the richness, diversity and composition of intestinal flora, and restoring the balance of Th17/Treg.

Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis / 中华医学杂志(英文版)

BACKGROUND@#Glioblastoma is one of the most common malignant brain tumors. Conventional clinical treatment of glioblastoma is not sufficient, and the molecular mechanism underlying the initiation and development of this disease remains unclear. Our study aimed to explore the expression and function of miR-873a-5p in glioblastoma and related molecular mechanism.@*METHODS@#We analyzed the most dysregulated microRNAs from the Gene Expression Omnibus (GEO) database and examined the expression of miR-873-5p in 20 glioblastoma tissues compared with ten normal brain tissues collected in the Zhejiang Tongde Hospital. We then overexpressed or inhibited miR-873-5p expression in U87 glioblastoma cell lines and analyzed the phenotype using the cell counting kit-8 assay, wound healing assay, and apoptosis. In addition, we predicted upstream and downstream genes of miR-873-5p in glioblastoma using bioinformatics analysis and tested our hypothesis in U87 cells using the luciferase reporter gene assay and Western blotting assay. The differences between two groups were analyzed by Student's t test. The Kruskal-Wallis test was used for the comparison of multiple groups. A P < 0.05 was considered to be significant.@*RESULTS@#The miR-873-5p was downregulated in glioblastoma tissues compared with that in normal brain tissues (normal vs. tumor, 0.762 ± 0.231 vs. 0.378 ± 0.114, t = 4.540, P < 0.01). Overexpression of miR-873-5p inhibited cell growth (t = 6.095, P < 0.01) and migration (t = 3.142, P < 0.01) and promoted cell apoptosis (t = 4.861, P < 0.01), while inhibition of miR-873-5p had the opposite effect. Mechanistically, the long non-coding RNA HOTAIRM1 was found to act as a sponge of miR-873-5p to activate ZEB2 expression in U87 cells.@*CONCLUSIONS@#We uncovered a novel HOTAIRM1/miR-873-5p/ZEB2 axis in glioblastoma cells, providing new insight into glioblastoma progression and a theoretical basis for the treatment of glioblastoma.

Xuebijing Injection () increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury.</p><p><b>METHODS</b>Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated.</p><p><b>RESULTS</b>The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01).</p><p><b>CONCLUSIONS</b>XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.</p>

Anti-proteolytic capacity and bonding durability of proanthocyanidin-biomodified demineralized dentin matrix / 国际口腔科学杂志·英文版

Our previous studies showed that biomodification of demineralized dentin collagen with proanthocyanidin (PA) for a clinically practical duration improves the mechanical properties of the dentin matrix and the immediate resin-dentin bond strength. The present study sought to evaluate the ability of PA biomodification to reduce collagenase-induced biodegradation of demineralized dentin matrix and dentin/adhesive interfaces in a clinically relevant manner. The effects of collagenolytic and gelatinolytic activity on PA-biomodified demineralized dentin matrix were analysed by hydroxyproline assay and gelatin zymography. Then, resin-/dentin-bonded specimens were prepared and challenged with bacterial collagenases. Dentin treated with 2% chlorhexidine and untreated dentin were used as a positive and negative control, respectively. Collagen biodegradation, the microtensile bond strengths of bonded specimens and the micromorphologies of the fractured interfaces were assessed. The results revealed that both collagenolytic and gelatinolytic activity on demineralized dentin were notably inhibited in the PA-biomodified groups, irrespective of PA concentration and biomodification duration. When challenged with exogenous collagenases, PA-biomodified bonded specimens exhibited significantly less biodegradation and maintained higher bond strengths than the untreated control. These results suggest that PA biomodification was effective at inhibiting proteolytic activity on demineralized dentin matrix and at stabilizing the adhesive/dentin interface against enzymatic degradation, is a new concept that has the potential to improve bonding durability.

Effect of quaternary ammonium methacrylates incorporation into a dental adhesive on the resistance of enzymatic degradation of resin-dentine interfaces / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of quaternary ammonium methacrylates incorporation into a dental adhesive on the resistance of enzymatic degradation of resin-dentine interfaces.</p><p><b>METHODS</b>Thirty caries-free extracted human third molars were randomly divided into three groups (n = 10): 2-methacryloxylethyl dodecylmethyl ammonium bromide (MAE-DB) incorporated adhesive served as the experimental group, pre-treatment with chlorhexidine (CHX) served as a positive control, Adper(TM) Single Bond 2 served as a negative control. The resin-dentin interfaces were prepared using total etch bond system. After storage in distilled water at 37 °C for 24 h, the bonded teeth were vertically sectioned into beams. Beams were respectively immersed in artificial saliva containing 2 g/L MMP-8 at 37 °C for 0 h, 24 h and 120 h (n = 30). Micro-tensile bond strength, failure modes and nanoleakage were examined.</p><p><b>RESULTS</b>There were no significantly differences of micro-tensile bond strength between groups before hydrolysis (P > 0.05). After the enzymatic hydrolysis of 24 h and 120 h, the micro-tensile bond strength of MAE-DB groups [(31.13 ± 8.77) MPa, (24.14 ± 6.64) MPa] were significantly higher than that of the negative control groups [(25.63 ± 6.90) MPa, (15.22 ± 6.57) MPa] (P < 0.05). Most of the failures were found in the base part of the hybrid layer in the negative control group, while failures occurred through the top of the hybrid layer in CHX and MAE-DB groups after the enzymatic hydrolysis.Specimens from each immediate group showed minor silver deposits in hybrid layer. After beams being enzymatic hydrolyzed for 120 h, it was shown that the silver nitrate uptake in the negative control group were significantly different from those in the CHX and MAE-DB groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Dental adhesive incorporation of MAE-DB could improve the anti-degrade ability of resin-dentin interfaces.</p>

Effect of casein phosphopeptide-amorphous calcium phosphate on the stability of resin-dentin bonds against pH cycling / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on the stability of resin-dentin bonds against pH cycling.</p><p><b>METHODS</b>Resin-bonded dentin specimens were prepared following manufacturers' instructions, and randomly divided into 3 groups. Among them, 2 groups experienced pH cycling, in which specimens applied CPP-ACP or distilled and deionized water (DDW) on the bonding interface, respectively. Microtensile bond strength (muTBS) testing, failure mode analysis, micromorphological and nanoleakage evaluation of bonding interface and elemental analysis within hybrid layer were performed after 15 days pH cycling. The other group was tested immediately after specimens' preparation without pH cycling.</p><p><b>RESULTS</b>No significant differences were found in muTBS between no pH cycling and pH cycling/CPP-ACP group. Their muTBS were both significantly higher than that of pH cycling/DDW group (P < 0.05). Mixed fractures were the most prevalent failure mode. The quality of hybrid layer in pH cycling/CPP-ACP group was better than that of pH cycling/DDW group, and the nanoleakage was also less severe. Comparing with pH cycling/DDW group, the atomic percentages of Ca in the other two groups were both significantly higher, while those of Ag were statistically lower (P < 0.05).</p><p><b>CONCLUSION</b>Local application of CPP-ACP can promote the stability of resin-dentin bonding interface against pH cycling and prolong bonding degeneration.</p>

Liangxuehuoxue Recipe inhibits expressions of tumor necrosis factor-α and transforming growth factor-β in the lung tissue of rats with X-ray exposure / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of Liangxuehuoxue Recipe (LXHXF), a compound traditional Chinese medicinal preparation, on the expressions of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in the lung tissue of rats exposed to X-ray radiation.</p><p><b>METHODS</b>Seventy-two Wistar rats were randomized into exposure group (group A, without treatment) and small-, middle- and high-dose LXHXF groups (groups B, C, and D treated with LXHXF at the daily doses of 9, 18, and 36 g/kg, respectively). After X-ray exposure of the right lung at 3 Gy twice a week for 5 consecutive weeks, the rats were sacrificed at the end of the 5th, 12th and 26th weeks, and the lung tissues were taken for immunohistochemistry of the expressions of TNF-α and TGF-β.</p><p><b>RESULTS</b>In group A, the expression of TNF-α reached the peak level at 5 weeks and TGF-β expression was the highest at 12 and 26 weeks. LXHXF, especially at the middle and high doses, obviously inhibited the expression of TNF-α at 5 weeks; the treatments also resulted in significantly lowered expressions of TGF-β at all the time points of observation as compared with those in group A (P<0.01). The high- and middle-dose groups exhibited no significant difference in the expression levels of TNF-α and TGF-β in the experiment (P>0.05).</p><p><b>CONCLUSION</b>Treatment with LXHXF can effectively inhibit TNF-α expression in the lung tissue in the early stage following radiation exposure, causing even more obvious inhibitory effect on TGF-β in the later stages. A higher dose of LXHXF produces more significant inhibitory effects on TNF-α and TGF-β expressions.</p>

Effect of Bushen Huoxue Decoction on dopamine D2 receptor in the brain of rats with Parkinson's disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD).</p><p><b>METHODS</b>A total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats.</p><p><b>RESULTS</b>BHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05).</p><p><b>CONCLUSION</b>BHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.</p>

Effect of Bufeishenqingre decoction on bronchial hyperresponsiveness-induced cough / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of traditional Chinese medicine preparations on bronchial hyperesponsiness (BHR)-induced cough.</p><p><b>METHOD</b>Sixty patients with cough due to BHR (shown by positive bronchial provocation test) were randomly divided into Chinese medicine group (n = 30) and control group (n = 30) to receive Bufeishenqingre decoction twice a day and 100 mg theophylline sustained-release capsules twice a day for one month, respectively. The changes of the clinical symptoms were observed during the treatment and bronchial infrared imaging was performed before and after the treatment.</p><p><b>RESULTS</b>The symptoms of patients in the Chinese medicine group were more effectively alleviated than those of the control group (P < 0.05). The difference in the temperature between the bronchial lesions and the surrounding normal mucosa changed more obviously in the Chinese medicine group (P < 0.01).</p><p><b>CONCLUSION</b>Bufeishenqingre decoction can relieve the symptoms and improve the abnormalities in infrared imaging of patients with BHR-induced cough.</p>

The study of early application with Dixiong Decoction (地芎汤) for non-small cell lung cancer to decrease the incidence and severity of radiation pneumonitis: A prospective, randomized clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of compound Dixiong Decoction (地芎汤, a Chinese herbal decoction) on early prevention of radiation pneumonitis.</p><p><b>METHODS</b>Forty-six patients with non-small cell lung cancer who were planning to receive radiotherapy were randomly assigned to the treatment group treated with the compound Dixiong Decoction and the control group treated with a commonly used herbal decoction which has the effects of supplementing qi and nourishing yin, clearing heat and detoxifying at the time of radiotherapy. Primary measure was the incidence of radiation pneumonitis after radiotherapy. Secondary outcomes included Watters clinical radiographic physiologic (CRP) dyspnea score, the Radiation Therapy Oncology Group (RTOG) grading score, Karnofsky Performance Status (KPS) score, and the application of corticosteroids.</p><p><b>RESULTS</b>The incidence of radiation pneumonitis in the treatment group was 10.0%, while that in the control group was 26.3% (P=0.0032). The Watters CRP dyspnea score and RTOG grading score in the treatment group were significantly =lower than those in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.01). The dosage of corticosteroids was smaller with a shorter duration of therapy in the treatment group than that in the control group.</p><p><b>CONCLUSION</b>The early application of the Chinese herbal decoction compound Dixiong Decoction can decrease the incidence of radiation pneumonitis, reduce the injury of the lung, and improve the life quality of the patients.</p>

Effects of Siwu tang on serum protein of blood deficiency using proteomic technique / 中国中药杂志

<p><b>OBJECTIVE</b>To research the effects of Siwu tang on serum protein of blood deficiency using proteomic technique and further explore its potential molecular mechanism to cure blood deficiency.</p><p><b>METHOD</b>The sera of normal, blood deficiency and cured group were collected. Proteomic protocol involving the high resolution two-dimensional polyacryamide gel electrophoresis, the computer-assisted image analysis, and the mass spectrometry was used to detect regulated protein by Siwu tang.</p><p><b>RESULT</b>Compared with normal group, there were 15 proteins changed, in which 11 increased and 4 decreased expressed proteins in sera could be recovered by Siwu tang. The up-regulated proteins involved haptoglobin, clusterin, complement component C4B and GTP binding protein 2, while the down-regulated proteins involved transthyretin and heamoglobin beta.</p><p><b>CONCLUSION</b>Siwu tang could regulate serum protein, which include immunology, apoptosis, DNA injury repair, and blood ingredients. This might be the mechanism of Siwu tang to cure blood deficiency.</p>

Effects of blood-cooling and promoting drugs on rats with radiation-induced lung injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of blood-cooling and promoting drugs (BCPD) on the dy-namic changes of collagens and the expressions of interleukin-6 (IL-6) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation-induced lung injury (RILI) to explore the effects and action mech-anism of BCPD in preventing and treating RILI.</p><p><b>METHODS</b>One hundred and sixty Wistar female rats were ran-domly divided into the radiation group, the treatment group, the blank control group and the drug control group. The rats in the first two groups received right hemithoracic fractionated radiation, and those in the treatment group were given BCPD. Rats in the other two groups were not irradiated and BCPD was given to rats in the drug control group. The rats were sacrificed in batches (8 of each group in every batch) at the 3rd, 5th, 8th, 12th and 26th week of the experimental period, and their lung was taken for observing the dynamic changes and distribution of collagen and the expressions of IL-6 and TGF-beta with HE staining, picrosirius red staining and immunohistochemical staining respectively.</p><p><b>RESULTS</b>The fibroblast proliferated obviously from the 3rd week after the first radiation in the radiation group, and the type I collagen and the proportion of type I and III collagen were significantly elevated along the time going and the radiation dose increasing, became significantly higher than those in the treatment group at all the time points (P <0.01). In the radiation group the expression of IL-6 and TGF-beta reached their peaks at the 8th and 12th week, respectively, and the levels was significantly lower in the treatment than that in the radiation group at any detecting time points (P <0.01).</p><p><b>CONCLUSION</b>BCPD applied in the early stage of radiation can suppress the inflammatory and fibrogenic cytokine expressions, inhibit the synthesis of collagens and adjust the proportion of type I and III collagen, so as to re-lieve the early-stage inflammatory reaction and the anaphase lung fibrosis in RILI rats.</p>

Experimental study on the prevention and treatment of radiation lung injury by blood-activating and stasis-dissipating drugs / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the pathological changes and the expression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation injury for exploring the mechanism of blood-activating and stasis-dissipating drugs in radiation injury prevention and treatment.</p><p><b>METHODS</b>One hundred and thirty SD female rats were randomly allocated into the simple irradiation group (n=60), the TCM herbs treatment group (n=60) and the blank control group (n=10). The right lung of all rats except those in the blank control group were irradiated by linear accelerator, 3 Gy each time, twice weekly, the maximum accumulated dose being 30 Gy. Ten rats in the two groups were randomly sacrificed at each of the 6 time points (1, 3, 5, 8, 12 and 26 weeks after repeated irradiation), their lung was harvested out, sliced and dyed with HE stain. The histological changes, levels of TNF-alpha and TGF-beta expression in the lung tissue were then observed by immunohistochemical technique.</p><p><b>RESULTS</b>The most serious acute radiation pneumonia was seen in the 5th week and pulmonary fibrosis was remarkable in the 26th week in the simple irradiation group, with the expressions of TNF-alpha and TGF-beta at different time phases enhanced significantly (P < 0.01). While in the TCM herbs treatment group, the pneumonia was milder, pulmonary fibrosis in late stage was not so obvious, and the expressions of TNF-alpha and TGF-beta significantly lower than those in the simple irradiation group (P < 0.01).</p><p><b>CONCLUSION</b>Blood-activating and stasis-dissipating drugs can inhibit expression of inflammation-inducing factors and fibrosis-inducing factors to lessen the inflammatory reaction of early radiation pneumonia, prolong the progression of radiation lung fibrosis, showing preventive and treating action on radiation lung injury.</p>