Middle-dose Group Research Articles

Molecular Composition, Digestion and Absorption Characteristics of Astaxanthin in Antarctic Krill Oil

The extraction of Antarctic krill oil enrich astaxanthins using n-hexane-ethanol solvent systems was studied, taking the total astaxanthin content, phospholipid content and yield of Antarctic krill oil as the investigation indexes. Meanwhile, the molecular species composition of astaxanthins in Antarctic krill oil which extracted under the optimized conditions were characterized and analyzed. Then the digestion process and bioaccessibility of astaxanthins in Antarctic krill oil were investigated by single-dose oral gavage with different doses of Antarctic krill oil, using ICR mice as model animals. Furthermore, the bioacceptability of astaxanthin from Antarctic krill oil and Haematococcus pluvialis were compared. The results showed that the 60%(V/V) n-hexane-ethanol solution was selected as the best solvent to extract Antarctic krill oil enrich astaxanthins. The astaxanthins in krill oil were mainly present as fatty acid esters, the relative percentages of astaxanthin diesters, monoesters, and free astaxanthin were 73.5%, 24.8%, and 1.62%. The astaxanthin diesters were hydrolyzed to monoesters or free from in the gastrointestinal tract. After 24 hours of gavage, the bioaccessibility of astaxanthin in low, middle and high dose groups was not significant, and the bioaccessibility of astaxanthin in Antarctic krill oil was about 74%. In addition, the bioaccessibility of astaxanthin in Antarctic krill oil was about 1.25 times of that in Haematococcus pluvialis oil. These results could provide a scientific basis for the rational production and the evaluation of dietary nutritional of Antarctic krill oil.

Subchronic nonylphenol exposure induced anxiety-like behavior and decreased expressions of regulators of synaptic plasticity in rats

Studies have shown that there were associations between endocrine disrupting chemicals (EDCs) and anxiety. Nonylphenol (NP) is an EDC with weak estrogen activity. This study aimed to clarify whether subchronic exposure of NP at environmental concentrations induces anxiety-like behavior, and effects of NP on the regulators (NMDAR2B, PSD-95, Synapsin1) expressions of synaptic plasticity in vivo and in vitro experiments. In vivo, 40 male SD rats were randomly divided into 4 groups (each with 10 rats): low dose (0.4 mg/kg/day, L-NP), middle-dose (4 mg/kg/day, M − NP), high-dose (40 mg/kg/day, H-NP) and corn oil (Control) groups. In vitro, HT22 cells were divided into a control group (Control), NP group (NP, 20 μM), glutamine acid receptor inhibitor group (MK-801, 10 μM) and MK-801 + NP group. The concentration of NP in the hippocampus rised with the increase of NP exposure concentration in the treatment groups (F = 7.542, P = 0.001). Compared with the control group, the residence time in the dark box after NP exposure had extended (F = 117.927, P < 0.01). The duration (F = 112.054, P < 0.01) and the number of times (F = 13.514, P < 0.01) to enter the closed arm in the NP exposure group significantly increased. There were more neurons degeneration and nuclear shrinkage in the M − and H– NP groups, while the average number of shrinked neurons increased with the increasing dose of NP exposure. The protein expressions of PSD-95 (F = 97.723, P < 0.01), Synapsin1 (F = 41.797, P < 0.01) and NMDAR2B (F = 3.440, P = 0.036) in the NP group were lower than those of the control. Simultaneously, the expressions of PSD-95, Synapsin1 and NMDAR2B in the hippocampus were down-regulated; the mRNA expression of PSD-95 (F = 19.950, P < 0.01), Synapsin1 (F = 3.498, P = 0.035) and NMDAR2B (F = 9.293, P < 0.01) genes in the hippocampus decreased in the M − and H-NP groups. In vitro, the trend of the fluorescence intensity expressed by PSD-95 (F = 2.606, P = 0.124) and Synapsin1 (F = 20.573, P < 0.01) among the groups was: MK-801 + NP group < MK-801 < NP group. The protein expressions of PSD-95 (F = 5.699, P = 0.022), Synapsin1 (F = 10.820, P = 0.003) and NMDAR2B (F = 6.041, P = 0.019) were down-regulated. These results suggested that subchronic exposure to environmental concentrations of NP induced anxiety, and reduced the protein and/or mRNA expressions of regulators of synaptic plasticity (PSD-95, Synapsin1, NMDAR2B).

Total Flavonoids of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signaling Pathway.

Total flavonoids of Rhizoma drynariae (TFRD), a Chinese medicine, is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good effects. Purpose of this trial was to explore efficacy of TFRD on bone graft’s mineralization and osteoblasts’ differentiation in Masquelet induced membrane technique in rats. Forty male Sprague-Dawley rats were randomly divided into high dose group (H-TFRD), middle dose group (M-TFRD), low dose group (L-TFRD) and control group (control). The critical size bone defect model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) spacer was implanted into the defect of right femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 12 weeks of bone graft, bone tissues in the area of bone graft were examined by X-ray, Micro-CT, hematoxylin-eosin (HE) and Masson trichrome staining to evaluate the growth of the bone graft. The β-catenin, c-myc, COL1A1, BMP-2 and OPN in bone graft were quantitatively analyzed by Western blot and Immunohistostaining. Osteoblasts were cultured in the medium containing TFRD. Cell Counting Kit-8 (CCK-8) method, Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, Western blot, RT-PCR and other methods were used to detect the effects of TFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signaling pathway. In vivo experiments showed that the growth and mineralization of bone graft in TFRD group was better. Moreover, the expression of Wnt/β-catenin and osteogenesis-related proteins in bone tissue of TFRD group was more than that in other groups. In vitro experiments indicated that osteoblasts proliferated faster, activity of ALP was higher, number of mineralized nodules and proteins related to osteogenesis were more in TFRD group. But blocking Wnt/β-catenin signaling pathway could limit these effects. Therefore, TFRD could promote mineralization of bone graft and differentiation of osteoblasts in a dose-dependent manner during growing period of the bone graft of induced membrane technique, which is partly related to the activation of Wnt/β-catenin signaling pathway.

Effect of Huangqi decoction on delaying renal cell apoptosis induced by 12C6+ ion irradiation in rats and its mechanism

Objective: To investigate the molecular protective mechanisms of Huangqi decoction inhibiting the apoptosis of renal cells in the 12C6+ radiation brain model rats. Methods: Fifty Wistar rats were randomly divided into five groups: normal control group, radiation alone model group, Huangqi decoction (high-dose, middle-dose and low-dose ) groups. The normal control group and the radiation alone group were treated with saline10 ml/(kg·d) by gavage, the Huangqi decoction treatment groups were treated with Huangqi decoction at the doses of 4.5, 9 and 18 g/(kg·d) by gavage respectively. After 7 d, except mice in normal control group, the brain of the rats in radiation alone model group, high-dose, middle-dose and low-dose Huangqi decoction group were radiated by 4 Gy 12C6+ ion once. The rats were killed by the femoral artery after irradiation 7 d. The pathomorphism changes of renal tissue were observed by HE, the IL-6 level in serum was detected by ELISA, the gene expressions of Bcl-2, Bax and caspase-3 in renal tissue were assessed by RT-PCR, and the protein expressions of Bcl-2, Bax, caspase-3 and NF-κB in renal tissue were analyzed by immunehistochemical staining. Results: Compared with normal control group, the body weight and kidney index were decreased significantly, the expression of Bcl-2 in renal tissue was decreased significantly, the serum content of IL-6 was increased obviously, and the expressions of Bax, caspase-3 and NF-κB in renal tissue were increased significantly in the radiation alone model group (P＜0.01). The mesangial cells proliferated obviously, interstitial vessels of renal tubules were dilated and congested obviously, the lumen of renal tubules was narrow and irregular in the radiation alone model group. As compared with the radiation alone model group, the body weight and the kidney index were increased obviously in high-dose Huangqi decoction group, the gene and protein expressions of Bcl-2 in renal tissue were increased significantly in Huangqi decoction intervention group(P＜0.05 or P＜0.01). whereas, the protein expressions of Bax and caspase-3 in renal tissue were decreased significantly in middle-dose and high-dose Huangqi decoction group, the serum content of IL-6 was decreased obviously, the gene expressions of Bax and caspase-3 in renal tissue were decreased significantly and the protein expression of NF-κB in renal tissue was decreased significantly in Huangqi decoction intervention group(P＜0.05 or P＜0.01). The proliferation of mesangial cells was improved and the contour of renal tubules was clear in high-dose huangqi decoction group. Conclusion: High-dose of huangqi decoction has protective effect on kidney in rats induced by 12C6+ radiation brain, the mechanism may be related to the regulation of Bcl-2/NF-κB signal pathway.

Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis.

Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups (p < 0.05). No significant difference was found between the OA and LD groups (p > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.

Effect of Run Ze Tonic in Mice with Kidney-Yin Deficiency

Purpose: To observe the effects of Run Ze Tonic on thyroid hormone, adrenal function, sex hormones and cyclic nucleotide of mice with kidney-yin deficiency. Methods: ICR mice were randomly grouped into normal control group, model group, Run Ze Tonic high dose group, the middle dose group and low dose group, male and female in half. The kidney-yin deficiency mice models were established by intragastric administration of levothyroxine sodium before intragastric administration of corresponding drugs once a day for 10 consecutive days. One day after the last administration, the effects were observed by measuring weight. And tetraiodothyronine (T4), triiodothyronine (T3), thyrotropin (TSH), corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) were tested by ELISA method. Results: Compared with the model group, the body weight, TSH level increased significantly (p <0.01, p<0.05), and T3, T4, ACTH level decreased significantly in high dose group (p <0.01, p <0.05). The E2 level in female decreased significantly in high dose group (p <0.01), the same as the ratio of E2/T (p <0.01). The T level in male increased significantly in high dose group (p <0.01), the same as the ratio of E2/T (p <0.01). And cAMP level decreased in the high dose group(p <0.05). Conclusion: Run Ze Tonic may play the role of nourishing yin and strengthening kidney by adjusting hormone level disorder, adrenal cortex function and balancing energy metabolism in endocrine system.

Pingyang Jiangya Fang pretreatment reduces the blood pressure of spontaneously hypertensive rats with Liver-Yang hyperactivity syndrome via ROS/Akt oxidative stress pathway.

ROS/Akt pathway oxidative stress refers to a procedural response that activates various stress-sensitive signaling pathways in the cell thereby inducing insulin resistance (IR), and is closely related to high blood pressure. This study aims to investigate the effects of Pingyang Jiangya Fang (PYJYF) on the ROS/Akt pathway oxidative stress response in spontaneously hypertensive rats (SHRs) with Liver-Yang hyperactivity syndrome. Except for the Wistar-Kyoto (WKY) and SHR groups, the other groups' rats were administered with Fuzi Decoction, to duplicated the model of hyperactivity of Liver-Yang. These rat's scleral color of deepens and become red, and rat's degree of irritability reached to above II degree. Compared with control group, rat's water consumption increased significantly, rotation tolerance time reduced significantly, pain threshold reduced significantly, rat tail vein systolic blood pressure (SBP) increased significantly. It shows that the model rats with hyperactivity of Liver-Yang have successfully replicated. Then, the corresponding drugs in the positive medicine group (candesartan cilexetil tablets) and the high, middle, and low dose groups of PYJYF (PYJYF-H, PYJYF-M, PYJYF-L) were administered. This work detected and analyzed behavior, SBP, renin-angiotensin system (RASS), expression of skeletal muscle angiotensin II type 1 receptor/angiotensin II type 2 receptor (AT1R/AT2R), IR index, renal/renal vascular/skeletal muscle tissue damage in each group. Moreover, we identified the target effect of point composition in the ROS/Akt signaling pathway. Unlike the WKY and SHR groups, the model group exhibited the phenotype of Liver-Yang hyperactivity syndrome, markedly increased SBP, hyper-RASS system, increased urine N-acetyl-β-Dglucosidase (NAG) and microalbuminuria (m-ALB), increased AT1R/AT2R ratio of skeletal muscle, IR, concomitant renal and skeletal muscle damage, as well as significant upregulation in the expression of ROS/ Akt signaling factor. PYJYF-H and PYJYF-M improved Liver-Yang hyperactivity syndrome, reduced SBP, the RASS system, urine NAG and m-ALB, AT1R/AT2R ratio, IR index, repair renal, renal vascular, and skeletal muscle tissue injury, as well as downregulated the expression of ROS/Akt signal factor. PYJYF reduces blood pressure by inhibiting ROS/Akt pathway oxidative stress and reducing IR.

Prevention of cisplatin-induced nausea and vomiting by seabuckthorn (Hippophae rhamnoides L.) seed oil: Insights at the level of orexin-A in rats.

Objective(s):Nausea and vomiting are perennial problems in cancer patients undergoing chemotherapy. Orexin-A (OXA) has been shown to regulate feeding and gastric motility. Seabuckthorn (Hippophae rhamnoides L.) seed oil (SSO) has been proved to promote digestion and bowel movements. We investigated whether SSO alleviated cisplatin-induced vomiting and its possible mechanism involved in OXA. Materials and Methods:Rats were randomly divided into normal control group (NCG), cisplatin group (CG), SSO low-dose group (SLG), SSO middle-dose group (SMG) SSO high-dose group (SHG), and ondansetron group (OG). Rats were pretreated respectively with SSO (0.850, 1.675, and 3.350 g/kg·BW) and ondansetron (2 mg/kg·BW) in SLG, SMG, SHG, and OG for 6 days, and the same volume of saline in NCG and CG groups. On the 6th day, cisplatin (6 mg/kg, IP) was administered in all groups except NCG. The cumulative food and kaolin intake, gastric emptying, plasma OXA level, OX1R mRNA and protein expression in the hypothalamus and brainstem, and OXA expression in the lateral hypothalamic area (LHA) were observed, and the HPLC method was used to analyze the composition of SSO. Results:Kaolin intake in cisplatin-induced vomiting rats was significantly reduced (P<0.05) and gastric emptying delayed by cisplatin was improved (P<0.05-0.01) by pretreatment with SSO. Plasma OXA concentration, OX1R expression in the hypothalamus and brainstem increased significantly (P<0.05–0.01). Furthermore, OXA expression in LHA also increased significantly (P<0.05). Conclusion:SSO prevents cisplatin-induced vomiting in rats, which is possibly involved in increasing peripheral and central OXA and the expression of OX1R in the hypothalamus and brainstem.

Non-target metabolomic analysis reveals the therapeutic effect of Saposhnikovia divaricata decoction on collagen-induced arthritis rats

Ethnopharmacological relevanceSaposhnikovia divaricata (SD), a Chinese crude drug, has long been recognized for therapeutic effect to rheumatoid arthritis (RA). At present, the mechanisms of SD treatment in RA have not been fully understood especially on the perspective of metabolomics.Aim of the study: To study the pharmacodynamic effects of Saposhnikovia divaricata decoction on CIA rats, and explore the therapeutic mechanism by metabolomics methods. Materials and methodsWistar rats were randomly divided into normal group, CIA model group, dexamethasone group and SD decoction groups (10 g crude drug/kg, 5 g crude drug/kg and 2.5 g crude drug/kg of SDD). Body weight, arthritis scores, serum cytokine levels and histopathological parameters of rats were assessed. A metabolomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) was established to collect the metabolic profiles of rats and explore the metabolic changes that occurred after SDD treatment. ResultsSDD showed its protective effect on the affected joints, especially in the middle dosage group of SDD. Eighteen and 13 potential biomarkers for the SDD treatment of CIA rats were identified in the plasma and urine, respectively. SDD could regulate the disturbed metabolic pathways including tryptophan metabolism, glycerophospholipid catabolism, primary bile acid biosynthesis and fatty acid metabolism. ConclusionsIn summary, SDD treatment could effectively alleviate symptoms of RA and regulate metabolic disorders in CIA rats.

Antitumor activity of flavonoids from Alpinia officinarum hance on gastric cancer

Introduction: To investigate antitumor activity and mechanism of flavonoids from Alpinia officinarum Hance against gastric cancer. Methods: Transplanted mouse fore-stomach carcinoma (MFC) tumor mice were divided into six groups: control group, model group, low dose (20 mg/kg), middle dose (40 mg/kg), and high dose (80 mg/kg) groups of TFAO and 5-Fu group. Mice were treated with TFAO or 5-Fu for 14 days, except those of control and model group. Tumor inhibitory rate, spleen, and thymus index were calculated. Contents of proliferating cell nuclear antigen, MMP-9, vascular endothelial growth factor, IL-1β, IL-6, and IL-17 in serum were detected. Effect of galangin on BGC-823 cell growth was detected. Cell apoptosis and cell cycle distribution were measured. Enzyme activity of Caspase-3, Caspase-8, and Caspase-9 was detected. Western blot was used to detect STAT3, Bcl-2, Bax, Caspase-3, Caspase-8, Caspase-9, CyclinB1, and CyclinD1 protein expression in BGC-823 cell. Results: Compared with model group, tumor weight of mice decreased significantly ( p &lt; .01) in 5-Fu group, low dose, middle dose, and high dose group of TFAO; thymus index of mice decreased significantly ( p &lt; .05) in 5-Fu group; and spleen index decreased significantly ( p &lt; .05) in low dose and middle dose groups of TFAO. Compared with model group, levels of PCNA, MMP-9, IL-1β, and IL-6 in serum of mice decreased obviously ( p &lt; .01) in all administration groups; levels of VEGF in serum of mice decreased obviously ( p &lt; .01) in low dose and high dose group of TFAO and 5-Fu group; and levels of IL-17 in serum of mice decreased significantly ( p &lt; .01) in low-dose and middle-dose groups of TFAO and 5-Fu group. Galangin could inhibit BGC-823 cell growth; accelerate apoptosis; block cell cycle; increase cell Caspase-3, Caspase-8, and Caspase-9 enzyme activity; upregulate expression of Caspase-3, Caspase-8, Caspase-9, and Bax; and downregulate expression of STAT3, CyclinB1, CyclinD1, and Bcl-2 protein. Conclusion: Flavonoids from A. officinarum showed antitumor activity in gastric cancer. Mechanisms may be associated with inhibition of tumor angiogenesis, tumor cell proliferation, and cancer-associated inflammation.

Thirteen-week inhalation toxicity study of 1-propanol in F344 rats

1-Propanol is a colorless volatile liquid at room temperature and is an important industrial alcohol. Workers are potentially exposed to it through inhalation during industrial activities, including manufacturing, sampling, filling, and mixing processes, as well as during cleaning, maintenance, and repair. Consequently, further information and/or testing for inhalation-related toxicological data is required to assess occupational risk. In this study, 80 (40 male and 40 female) F344 rats were exposed to 1-propanol vapors for 13 weeks (6 h a day, 5 days per week) at target concentrations of 0, 500, 1,600, and 5200 ppm in a whole-body inhalation chamber system. Clinical signs, mean body weight changes, food consumption, hematology, blood biochemistry, necropsy, organ weight, and histopathological findings were observed. The exposure concentrations in chambers were 501.30 ± 9.54 ppm, 1605.43 ± 66.55 ppm, and 5202.19 ± 102.74 ppm for the low, middle, and high dose groups, respectively. No changes related to 1-propanol were observed, including histopathological findings, except for mean body weight changes. The significant decrease in mean body weight at a high dose was not considered to be an adverse effect. Based on these results, the no observed adverse effect concentration of 1-propanol was estimated to be 5202.19 ppm.

Relationship between Gastric Blood Perfusion and Gastric Mucosal Injury Induced by Acute Cerebrovascular Disease in Rats

This study aims to discuss the relationship between gastric perfusion and gastric mucosal injury induced by acute cerebrovascular disease in rats. Healthy adult male Wistar rats weighing 280-320 g are randomly divided into the following 4 groups: middle cerebral artery occlusion-reperfusion group, middle cerebral artery occlusion -sham group, gastric ischemia-reperfusion group and gastric ischemia-sham group, with 12 in each group. In gastric ischemia-reperfusion group, the similar changes occur to the mucous membrane of the rats, such as hyperaemia, edema, spotty or patchy hemorrhage and partial mucous exfoliation. There is no significant difference between middle cerebral artery occlusion-reperfusion group and gastric ischemia-reperfusion group in the number of gastrin cells and the expression of gas, but the number of gastrin cells and the expression of gas are significantly higher than those of their corresponding sham operation group, resulting in statistically significant difference. The gastric mucosal blood flow is significantly increased in the middle and high dose groups, which has significant difference compared with normal saline group (p<0.05). One of the important mechanisms of Calcitonin gene-related peptide protecting ischemic gastric mucosal injury is to increase gastric mucosal blood perfusion and improve microcirculation.

Study on Effect of Vitexicarpin on the Biological Behavior of Colorectal Cancer Cells by Circ_0000419/MicroRNA-224

To investigate the effect and molecular mechanism of vitexicarpin on the biological behavior of colorectal cancer cells is the objective of the study. The human epithelial cell line Caco-2 cells were divided into control group, low, middle and high dose groups of vitexicarpin, plasmid cloning DNA-circ_0000419 group, plasmid cloning DNA group, anti-microRNA-224 group, anti-microRNA-224-negative control group, vitexicarpin+small interfering-circ_0000419 group and vitexicarpin+microRNA-224 group. Cell activity was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Colony formation number was detected by plate clone formation experiment. Apoptosis was detected by flow cytometry. Scratch test was used to detect the migration distance of cells. Transwell method was used to detect the number of invasive cells; protein expression was detected by western blot; the expression levels of circ_0000419 and microRNA-224 were detected by real-time fluorescence quantitative polymerase chain reaction; dual-luciferase reporter assay was used to detect the targeting relationship between circ_0000419 and microRNA-224. After treatment with low, middle and high doses of vitexicarpin, the viability of Caco- 2 cells decreased, the number of colony formation decreased, the apoptosis rate increased, the migration distance decreased, the number of invasive cells decreased, the expression level of E-cadherin increased, the expression level of N-cadherin decreased, the expression level of circ_0000419 increased and the expression level of microRNA-224 decreased (p<0.05). Overexpression of circ_0000419 or inhibition of miR-224 expression decreased Caco-2 cell viability, decreased colony formation, increased apoptosis rate, decreased cell migration distance, decreased invasive cell number, increased expression of E-cadherin and decreased expression of N-cadherin (p<0.05). Interference with circ_0000419 or overexpression of microRNA-224 reverses the effects of vitexicarpin on proliferation, apoptosis, migration and invasion of Caco-2 cells; circ_0000419 targets the regulation of microRNA-224 expression. Vitexicarpin can inhibit the malignant biological behavior of colorectal cancer cells by circ_0000419/microRNA-224.

Effect of Salviae Miltiorrhizae Radix et Rhizoma on diversity of intestinal flora in diabetic nephropathy rats

This study aimed to explore the effect of Salviae Miltiorrhizae Radix et Rhizoma, its stems and leaves on the diversity of intestinal microflora in rats with diabetic kidney injury. Diabetic rats model was established by feeding high glucose and high fat diet and 5% glucose solution with intraperitoneal injection of 30 mg·kg~(-1) streptozocin(STZ). The rats were randomly divided into normal group, model group, irbesartan control group, Huangkui Capsules control group, as well as low, middle and high dose groups of Sal-viae Miltiorrhizae Radix et Rhizoma, its stems and leaves. After administration for 2 weeks, 16 S rRNA technique was used to analyze the diversity of intestinal microflora in the feces of each group. The results showed rats in the model group developed renal tubular epithelial vacuole degeneration and a large amount of inflammatory cell infiltration in the renal interstitium. A small amount of inflammatory cell infiltration was seen in each administration group. The kidney structure of rats in irbesartan group, Huangkui Capsules group, high-dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem water extract, as well as high dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem ethnol extract group was close to the normal group. The diversity and structure of intestinal flora in the model group were significantly different from those in the normal group. Each administration group improved the fecal flora diversity in rats with diabetic kidney injury to a certain extent, especially the high dose of Salviae Miltiorrhizae Radix et Rhizoma and its stems water extract. Different flora were found in feces of diabetic nephropathy model rats on class, order, family and genus levels. On families and genera levels, the relative abundance of Bifidobacterium, Turicibacter, Peptostreptococcaceae, Desulfovibrio, and SMB53 showed an upward trend in model group, but that of Lactobacillus, Clostridium, Rikenella, Rumen fungi showed a downward trend. The administration groups can improve the relative abundance of the above intestinal flora in the model rats to a normal-like level. The results of this study provide a reference for resource utilization and further development of Salviae Miltiorrhizae Radix et Rhizoma.

Effects of Mecobalamin on Cerebral Ischemia-Reperfusion Injury of Spontaneously Hypertensive Stroke Prone Rats

We aimed to evaluate the effects of mecobalamin on the cerebral ischemia-reperfusion injury of spontaneously hypertensive stroke prone rats. 72 male rats were randomly divided into control group, model group, nimodipine group, high-dose mecobalamin group, middle-dose mecobalamin group and low-dose mecobalamin group (n=12). All groups were administrated intragastrically every morning once a day for 7 continuous days. The model of 2 h of focal cerebral ischemia and 24 h of reperfusion was established by blocking middle cerebral artery. Neurological deficits were graded with reference to the Longa method. Cerebral edema was determined using the wet-dry weighing method. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining and the levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 were measured by radioimmunoassay. High and middle-dose mecobalamin significantly reduced the volume of cerebral infarction, alleviated cerebral edema and improved nerve function compared with those of the model group (p<0.05). Compared with the model group, high and middle-dose mecobalamin significantly reduced the levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 in cerebral tissue (p<0.05). Mecobalamin protected spontaneously hypertensive stroke prone rats from cerebral ischemia-reperfusion injury, which may be related to the decreased levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 in cerebral tissue.

Amygdalin isolated from Amygdalus mongolica protects against hepatic fibrosis in rats.

The aim of this research was to investigate the effect of amygdalin on hepatic fibrosis in rats. Amygdalin was purified and identified from the seeds of Amygdalus mongo lica. Sprague Dawley rats in the control and model groups were administered water. Sprague Dawley rats were divided into the low-, middle-, and high-dose amygdalin groups that received 20, 40, and 80 mg kg-1 amygdalin, respectively. whereas the silymarin group was treated with 50 mg kg-1 silymarin. The control and model groups were administered water. Liver tissue analysis revealed significantly lower activities of ALT, AST, ALP, SOD, and MDA in the drug-treated groups compared to the model group. Serum analysis revealed significantly lower HYC and C-IV in the middle-dose amygdalin-treated group compared to the model group. The histopathological changes were less severe in the drug-treated groups as observed by the formation of pseudolobuli and decreased collagen fiber deposition. Hepatic fibrosis-related genes were expressed at significantly lower levels in the amygdalin-treated groups than in the model group. Amygdalin from A. mongolica represents a therapeutic candidate for hepatic fibrosis prevention and treatment.

Effect of vitamin D3 supplementation during pregnancy on high risk factors - a randomized controlled trial.

Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect. From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels. In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable. Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Two-weeks repeated-dose oral toxicity study of Pediococcus acidilactici J9 in a mice model

BackgroundHelicobacter pylori (H. pylori) is an important pathogen that causes chronic gastritis and peptic ulcer, and is related to the development of gastric carcinoma. Several chemicals, including antibiotics, have been used to eradicate H.pylori. However, more studies are yet requred to accomplish a sufficient therapy. Pediococcus acidilactici (P. acidilactici) J9 were studied for inhibition of binding of H.pylori binding to human gastric cell lines. This study was performed in order to investigate the repeated-dose toxicity of P. acidilactici J9 in male and female mice.ResultsC57BL/6 male and female Mus musculus were divided into four groups (n = 10 in each group). P. acidilactici J9 was administered daily by oral injection of vehicle control at dosage levels to a low-dose group (500 mg/kg/day), middle-dose group (1000 mg/kg/day), and high-dose group (2000 mg/kg/day) for 2 weeks. After 14 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathology exam. There were no bacterial-related deaths or abnormal clinical signs in either gender of mouse. The data was observed during the period in terms of body weight, food intake, and water consumption. Also, no alterations in organ weights upon administration of P. acidilactici J9 alone were observed. The adhesion and growth of H. pylori were inhibited by a 24 h treatment of H. pylori and P. acidilactici J9 on adenocarcinoma gastric (AGS) cells, which are gastric cancer cells. Compared to the control group (AGS cell and H. pylori), the number of H. pylori analyzed by FACS significantly (p < 0.01) decreased after incubation of AGS cell with P. acidilactici J9 for 24 h.ConclusionsThese results suggest that the oral application of P. acidilactici J9, up to a dosage level of 2000 mg/kg/day, causes no adverse effects in both male and female mice. P. acidilactici J9 inhibits the adhesion of H.pylori to AGS cancer cells. When used as probiotics, P. acidilactici J9 may help decrease the occurrence of gastritis and reduce the risk of H.pylori infection with promising safety issues.

The Effects of Daily Melatonin Gavage on Reproductive Activity in the Male Syrian Hamsters.

The proper administration of melatonin has well been documented to induce testicular regression in seasonal breeding animals. The subcutaneous injections of melatonin in the afternoon, not in the morning, consistently occurred testicular involution in the male Syrian (golden) hamsters whose reproductive activity is regulated by the photoperiod. But the effects of daily melatonin via gavage have not been estimated. Golden hamsters housed in long photoperiod (LP) were divided into 5 groups: the control animals housed in LP or in short photoperiod (SP) and animals treated daily with low (15 μg), middle (150 μg), and high dosages (1,500 μg) of pure melatonin by using gavage in the evening for 8 weeks. As results, LP control animals had large testes and SP controls displayed small and entirely regressed testes. The animals treated with various dosages of melatonin showed collectively degenerating effects on the weights of testes, epididymides, and seminal vesicles in the middle and high dosage groups, with the individual differences as well. The high dosages induced testicular regression in more proportion than the middle dosages did. The low dosage had large testes like the LP control animals. The small and inactive testes shown in some animals of both middle and high groups presented the complete regression as those of the animals maintained in SP. These results strongly suggest that the administrations of melatonin lead to testicular involution in the male golden hamsters when it is administered through gavage.

Effect of Cyclocarya paliurus polysaccharides on streptozotocin-induced diabetic nephropathy in rats.

To investigate the efficacy of Cyclocarya paliurus (C. paliurus) polysaccharides on stre- ptozotocin-induced diabetic nephropathy in rats. Rats were divided into 6 groups, including group of normal control, group of diabetic control, group of metformin treatment, low-dose group of C. paliurus polysaccharides treatment, middle-dose group of C. paliurus polysaccharides treatment and high-dose group of C. paliurus polysaccharides treatment. Histological analysis of kidney was analyzed using hematoxilin and eosin. Levels of blood glucose, creatinine, urea, uric acid were determined by spectrophotometry. Anti-oxidative enzymes were measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Advanced glycation end products (AGEs) and transforming growth factor-β1 (TGF-β1) level was measured by ELISA. Abnormal changes were observed in the group of diabetic control characterized by atrophy of the renal glomeruli with hypercellularity, congestion of glomerular tufts, dilation of the renal spaces, and degeneration of renal tubule. Compared with that of normal group, blood glucose, creatinine, urea, uric acid level was significantly increased in the group of diabetic control. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase level was significantly decreased, but AGEs and TGF-β1 level was significantly increased. By contrast, administration of C. paliurus polysaccharides and metformin could reverse the above-mentioned results of the group of diabetic control, especially in the high-dose group of C. paliurus polysaccharides. Our findings suggest that C. paliurus polysaccharides may play a protecting role for nephropathy of diabetic rats by lowering glucose, creatinine, urea, uric acid level, enhancing the antioxidative ability, and reducing AGEs and TGF-β1 expression.