Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments / 中国中药杂志

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Expression of thyroid-stimulating hormone receptor in mammary gland tissue of lactating rats / 中国地方病学杂志

Objective To observe the protein and mRNA expression of thyroid-stimulating hormone receptor (TSHR) in mammary gland tissue of lactating rats,and to explore iodine uptake mechanism.Methods Eighty adult Wistar rats (60 female and 20 male),weighting 210-250 g were selected.All female Wistar rats were randomly divided into 6 groups according to their body mass:normal non-pregnant group,lactating for 5-,10-,15-and 20-day groups and weaning for 5 days group,10 rats in each group.All rats were fed with conventional fodder and tap water freely.In addition to the normal non-pregnant group,other five groups of female and male rats were mated at 3 ∶ 1,respectively.Then the rats in all groups were killed on the 5th,10th,15th and 20th day after lactation and on the 5th day after weaning to get the mammary gland tissue.The protein and mRNA expression of TSHR were determined by immunohistochemical staining and real-time quantitative PCR.Results TSHR protein was expressed in mammary acinar and ductal epithelial cytoplasm.The expression of TSHR in mammary gland showed significant differences between groups (x2 =14.612,P ＜ 0.05),the staining intensity of mammary gland tissue in normal non-pregnant rats(weak,n =4; moderate,n =6) was weaker than that of lactating for 5 days(weak,n =2; moderate,n =3; strong,n =5) and 10 days groups(barely detectable,n =1;moderate,n =4; strong,n =5; x2 =4.113,5.250,all P＜ 0.05).The expression of TSHR mRNA in mammary gland showed significant differences between groups(F=20.488,P ＜ 0.05); the expression of TSHR mRNA in lactating for 10 days group(0.31 ± 0.06) was higher than that of lactating for 5 days group(0.22 ± 0.04,P ＜ 0.01),and the expression of lactating for 15 days group (0.16 ± 0.08) was significantly lower than that of lactating for 5 days group (P ＜ 0.05).Conclusions TSHR is widely expressed in mammary gland of lactating rats.The iodine uptake of mammary gland is enhanced in early lactation period when the body may be more susceptible to iodine deficiency,therefore iodine should be supplemented reasonably.

Therapeutic efficacy of hyperbaric oxygen on traumatic brain injury in the rat and the underlying mechanisms / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of hyperbaric oxygen (HBO) treatment on the activation of astrocytes and the expression of glia-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in the brain after traumatic brain injury (TBI).</p><p><b>METHODS</b>54 male SD rats were randomly divided into three groups (n = 18): sham-operated, TBI and HBO treatment groups. TBI was induced with Feeney's method, bone window was opened without strike on the brain tissue in the sham-operated group. HBO group rats received HBO treatment for 60 min in the hyperbaric chamber containing O2 100% at 3 ATA. When neurological functions were measured 48 h after TBI, rats were decapitated, the brain water content of 18 rats was measured, 18 brains were sliced for the morphological observation after Nissl staining and for the immunohistochemistry staining of astrocyte markers glial fibrillary acidic protein (GFAP), vimentin and S100, and the other 18 brains of injured side were used for Western blot analysis of GDNF and NGF.</p><p><b>RESULTS</b>HBO treatment reduced the neurological deficit, brain water content and hippocampal neuronal loss. In the observed cortex and hippocampal area astrocytes were activated, the cell number of positive expression of astrocyte markers GFAP, vimentin and S100 was increased, and the expression of GDNF and NGF was elevated after TBI. However, these indices were all enhanced further after the HBO treatment.</p><p><b>CONCLUSION</b>It is suggested that HBO may be an effective therapy for TBI and upregulation of the expression of GDNF and NGF may underly the effect of HBO.</p>

Effective dose and time window of ginseng total saponins treatment in rat after traumatic brain injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the neuroprotective effect, effective dose and time window of ginseng total saponins (GTS) treatment in rat after traumatic brain injury (TBI).</p><p><b>METHODS</b>The modified Feeney's method was used to establish TBI model in rat. GTS was treated intraperitoneally. The neurological function and histological morphology of brain tissue were observed.</p><p><b>RESULTS</b>Different doses of GTS were used 6 h after TBI. The neurological and histological results showed that: compared with the TBI group, significant efficacy was observed 2 - 14 days after injury with GTS treatment at 10, 20, 40, 60 and 80 mg/kg (P < 0.05); The effects of GTS at 20, 40, and 60 mg/kg were better than those of GTS at 10 and 80 mg/kg. During the research on the time window of GTS intervention, GTS (20 mg/kg) showed significant effect when used at 3 h and 6 h after TBI; however 12 h, 24 h after TBI, application of GTS did not exert any significant effect.</p><p><b>CONCLUSION</b>GTS intervention after TBI could reduce brain damage and promote recovery of the neurological function. Among doses of GTS 5 - 80 mg/kg, 20 - 60 mg/kg is the best dose limit. The effective time window of GTS is 6 h after TBI.</p>

Study on the effects of different vitamin A levels on thyroid cell apoptosis and related gene expression of mice taking excessive iodine / 中国地方病学杂志

Objective To explore the effects of different vitamin A(VA) levels on thyroid cells apoptosis and its gene expression of mice taking excessive iodine. Methods Kunming mice were randomly divided into 6 groups according to body weight 3 weeks after born: normal control(NI) group, high iodine(HI) group, low vitamin (LVA) group, high iodine plus low vitamin A(HI+LVA) group, high iodine plus vitamin A1 (HI+VA1) group, high iodine plus vitamin A2(HI+VA2) group. The VA was given in food(4000,4000,0,0,8000,16 000 U/kg), and the iodine was given as potassium iodate in water (I-:50,3000,50,3000,3000,3000 μg/L). The apoptosis was tested using in situ end labehng(TUNEL) method. Reverse transcription polymerase chain reaction (RT-PCR) were used to measure the level of mRNA of apoptosis gene(Fas, FasL, Bcl-2) in tissues. Results Apoptotic index measured by TUNEL method was rising along with the mice age. Compared to NI group[(14.09±5.68)%], apoptotic index was significantly increased in HI[(20.91±9.57)%], HI+LVA[(20.29±9.90)%]and HI+VA2 [(19.51±8.25)%]groups in the three months(P < 0.05). Compared to NI group[(16.80±9.90)%], apoptotic index was significantly increased(P < 0.05) in HI[(23.22±8.58)%],LVA[(22.56±6.17)%],HI+LVA [(25.99±9.62)%],HI+VA1 [(21.65±7.74)%]groups in the six months. Compared with the NI group(Fas: 1.29±0.25,1.27±0.26; FasL: 1.60±0.13,1.65±0.13), the mRNA levels of Fas and FasL in HI group(Fas: 1.57±0.36,1.49±0.35; FasL: 1.85±0.46,1.84±0.32) were increased, but the differences were not remarkable(P > 0.05) in the three and six months. Compared with the HI group, the mRNA levels of Fas in HI+ VA1, HI+VA2(1.33±0.35, 1.30±0.26) groups were decreased to the level in NI group in the six months. The mRNA levels of Fas and FasL were not different (P > 0.05) between HI+LVA(I.60±0.27,1.88±0.46) and HI groups in the three months. The mRNA levels of Bcl-2 were not remarkably differences in the three months (1.05±0.19,0.96±0.33,0.95±0.26,1.18±0.27,1.10±0.19,0.98±0.36, all P > 0.05), and in the six months (1.35±0.28,1.60±0.25,1.48±0.18,1.71±0.26,1.66±0.29,1.56±0.35, all P > 0.05). Conclusions Excessive iodine can cause thyroid cells apoptosis in mice. Supplementation of suitable amount of VA can regulate the levels of the apoptosis-related genes expression, and partly antagonize the apoptosis caused by high iodine.