Abstract: Objective To explore the effects of N-acetyl-seryl-aspartyl-lysyl-proline ( Ac-SDKP) on alveolar type II epithelial cellular senescence during experimental silicosis. Methods The HOPE-MED8050 dynamic silica dust exposure control system was applied to establish a rat model of silicosis, and the experimental silicosis rats were divided into the control, dust-treated and Ac-SDKP post-treatment groups. MLE-12 cells were cultured in vitro, and the experimental cells were divided into the control, SiO2 -induction, Ac-SDKP and SiO2 + Ac-SDKP groups. Sirius red staining was used to observe collagen deposition in the lung tissue; immunofluorescence staining was used to detect the location of p21, and immunoblotting was used to detect type I collagen (Col I) expression, p-capillary dilatation ataxia mutant kinase (ATM) , p-capillary dilation ataxia (ATR) , p-p53, p21 and p16. Results The lung tissue of rats in the silicosis group could be observed with silicon nodules and collagen deposition. Immunofluorescence staining result showed that p21 was mainly localized in alveolar type II epithelial cells. Immunoblotting result showed upregulated Col I, p- ATM, p-ATR, p-p53, p21 and p16 protein expression levels in the lung tissue. Compared with those of the dust-treated group, the number and area of the silicon nodules in the lungs of the Ac-SDKP post-treated group were significantly reduced, and the protein expression levels of Col I, p-ATM, p-ATR, p-p53, p21 and p16 in the lung tissue were decreased (P<0. 05) . Compared with those of the control group, the Col I, p-ATM, p-ATR, p-p53, p21 and p16 levels in MLE-12 cells of the SiO2 -induced group were upregulated. Compared with those of the SiO2 -induced group, the Col I, p-ATM, p-ATR, p-p53, p21, p16 expression levels were downregulated in the SiO2 + Ac-SDKP group ( P< 0. 05) . Conclusions Ac-SDKP reduced collagen deposition by inhibiting activation of senescence-related signals in alveolar type II epithelial cells.

Abstract: Objective To study the mechanism by which sodium aescinate (SA) reduces the areas of myocardial infarction area and no-reflow through the p38MAPK pathway in rats. Methods Adult male Sprague-Dawley rats were randomly divided into seven groups as follows: control, ischemia-reperfusion ( I/ R), I/ R+SA, blank adenovirus+I/ R, p38MAPK adenovirus+I/ R, blank adenovirus+I/ R+SA, and p38MAPK adenovirus+I/ R+SA. The myocardial I/ R model was established by ligating the anterior descending branch of the left coronary artery. Intervention comprised intraperitoneal injection of SA or local injection of adenovirus. Staining was used for detection as follows: thioflavin S for myocardial no- reflow area, nitrotetrazolium chloride blue for myocardial infarction area, and terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptosis. Enzyme-linked immunosorbent assay was used to detect interleukin ( IL-1β), tumor necrosis factor (TNF-α) and intercellular adhesion molecule (ICAM-1). Western blot was used to detect the expression of Bax, cleaved caspase-3 and phosphorylated p38 MAPK (p-p38 MAPK). Results Compared with the I/ R group, the areas of myocardial no reflow and infarct were significantly reduced, and there were significant decreases in the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, and the expression of Bax, cleaved caspase-3 and p-p38 MAPK (P<0. 05). Compared with the blank adenovirus+I/ R group, the areas of myocardial no reflow and infarct were significantly enlarged, and there were significant increases in the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, and the expression of Bax, cleaved caspase-3 and p-p38MAPK, in the p38MAPK adenovirus+I/ R group (P<0. 05). Compared with the blank adenovirus+I/ R+SA group, the areas of myocardial no reflow and infarct were significantly enlarged, and the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, as well as the expression of Bax, cleaved caspase-3 and p-p38MAPK, were significantly increased in the p38MAPK adenovirus+I/ R+SA group (P<0. 05). Conclusions SA reduced the myocardial infarction area and no-reflow area of rats after myocardial I/ R. The molecular mechanism for SA involves inhibition of the p38MAPK pathway to mediate the inflammatory response and apoptosis.

Abstract: Objective To establish a steatosis model in Mongolian gerbil primary liver cells and to evaluate the effect of Pnpla3 knockdown and Ganoderma lucidum triterpenic acid (GLTA) on lowering lipid content. Methods Primary gerbil liver parenchyma cells were isolated and cultured, and a liver steatosis model was induced by palmitic acid (PA4; 400 μmol / L). Three interfering RNA vectors targeting three Pnpla3 exons were constructed and stably transfected into parenchyma liver cells. The efficiency of Pnpla3 interference was determined. Cells were cultured with high (1 μmol / L), medium (0. 1 μmol / L) and low (0. 01 μmol / L) doses of GLTA and with the positive control drug, methionine (7 μmol / L), and triglyceride (TG) content was determined with and without Pnpla3 knockdown. Results Within 24 hours of induction, PA increased the number of lipid droplets and most cells were of normal shape. siRNA2, designed against the second exon of Pnpla3, had the best knockdown effect and interference efficiency was higher than 70%. Pnpla3 knockdown reduced intracellular TG content. Medium and high dose GLTA had obvious lipid-lowering effects (P< 0. 01), and Pnpla3 knockdown and GLTA had cumulative effects (P< 0. 01). Conclusions A lipid transformation model in primary gerbil hepatocytes was established. GLTA inhibited or reduced the TG content in cells after Pnpla3 knockdown, and the lipid lowering effect of GLTA was associated with the expression of Pnpla3 in two KEGG pathways ( ko00561 and ko00564), which are related to phospholipid metabolism.

Abstract: Objective To observe the effect of gypenosides (GYPs) on brain injury in septic rats and explore its mechanisms. Methods Sprague-Dawley rats were divided into the sham, sepsis-associated encephalopathy ( SAE), GYPs, GNE-317, and GYPs + GNE-317 groups. The SAE model was constructed via cecal ligation and perforation. Two hours after establishing the model, the rats were administered normal saline, normal saline, 200 mg / kg GYPs solution, 40 mg / kg GNE-317 solution or 200 mg / kg GYPs + 40 mg / kg GNE-317 solution, respectively, by irrigation at 2 mL/ d, continually administered for 3 days. The reflex test was used to evaluate the rats’ neural behavior, then the rats were killed and their hippocampuses were removed, hematoxylin and eosin staining was used to observe the pathological damage to the hippocampus, TUNEL testing was used to detect apoptosis in the hippocampus, MDA levels and SOD activity were detected using kits, and the expressions of phosphatidylinositol-3-kinase ( PI3K), protein kinase B ( Akt), p-Akt, apoptosis regulator Bax, Bad and caspase-3 proteins were detected via Western blot. Results Rats in the sham group were in good condition, and the morphology and structure of the hippocampal neurons were normal. Rats in the SAE group exhibited somnolence, lack of spontaneous activity, and diffuse neuronal damage. Rats in the GYPs group exhibited normal activity and neuronal morphology. Rats in the GNE-317 group exhibited worse activity and neuronal morphology than that of the SAE group. Rats in the GYPs + GNE-317 group showed similar symptoms to those of the SAE group. Compared with those of the sham group, the proportion of apoptotic cells, the MDA levels, and the expressions of cleaved-caspase-3, Bax and Bad were higher in the SAE group (P< 0. 05), whereas these indexes were lower in the GYPs group than in the SAE group (P< 0. 05), higher in the GYPs + GNE-317 group than in the GYPs group, and lower in the GYPs + GNE-317 group than in the GNE-317 group (P< 0. 05). Compared with those of the sham group, the neurobehavioral score, SOD activity, PI3K and p-Akt levels were lower in the SAE group (P< 0. 05) and higher in the GYPs group than in the SAE group (P< 0. 05). These indexes were lower in the GYPs + GNE-317 group than in the GYPs group and higher than those in the GNE- 317 group (P< 0. 05). Conclusions GYPs promoted activation of the PI3K/ Akt pathway in the hippocampus, inhibited the release of downstream apoptogenic factors, reduced oxidative stress, and alleviated brain injury in SAE-induced rats.

Abstract: Objective To study the effects of dioscin on Bel-7402 and LO2 cell proliferation and apoptosis and its possible mechanisms. Methods Bel-7402 and LO2 cells were exposed to 0. 5~ 16 μmol / L dioscin for 24 h, and inhibition of cell proliferation was examined via MTT assay. Morphologic changes in the cells were quantified using an inverted microscope, and Hoechst 33258 staining was used to observe morphological changes in the apoptotic cells. Changes in the mitochondrial membrane potential were measured using JC-1 staining. Bcl-2 and Bax expression were detected via western blot. Results Compared with the negative control group, Bel-7402 and LO2 cell proliferation was significantly inhibited dose-dependently after exposure to all concentrations of dioscin. The IC50 of the Bel-7402 cells was 2. 04 μmol / L; the IC50 of the LO2 cells was 2. 76 μmol / L. Compared with those of the negative control group, the cells showed varying degrees of distribution, density reduction, roundness, exfoliation, death and necrosis induced by 1 and 2 μmol / L of dioscin. The cell boundary was blurred and induced cell apoptosis. JC-1 staining result showed that the mitochondrial membrane potential was significantly decreased in both cell lines after treatment with dioscin ( P< 0. 01). Western blot result showed that dioscin significantly increased Bax expression and inhibited Bcl-2 expression in both cells lines ( P< 0. 05; P<0. 01). Conclusions Dioscin inhibited Bel-7402 and LO2 cell proliferation in vitro. The possible mechanism may have been that dioscin increased Bax expression, inhibited Bcl-2 expression, and induced apoptosis; thus, dioscin may induce liver injury during development of its anti-hepatocarcinoma functions.

Abstract: Objective To investigate the effect of ursolic acid on apoptosis and migration of lung cancer A549 cells by regulating miR-373-3p. Methods We used an MTT assay to detect the toxic effects of ursolic acid on A549 lung cancer cells. AnnexinⅤ-FITC/ PI double staining and flow cytometry were used to detect the effect of ursolic acid on A549 cells transfected with miR-373-3p. Real-time fluorescence quantitative PCR was used to detect the expression level of miR- 373-3p in A549 cells in the ursolic acid dosing group and the transfected miR-373-3p mimics group. RT-PCR and Western blot were used to detect mRNA and the protein expression of the downstream target gene, TXNIP, which is regulated by miR-373-3p under the action of ursolic acid. The scratch text was used to evaluate miR-373-3p cell migration ability. Results Ursolic acid significantly decreased the growth viability of A549 lung cancer cells (P<0. 05), with an IC50 of 60 μmol / L. Transiently transfected miR-373-3p mimics up-regulated the expression of miR-373-3p in A549 cells ( 24 h, 11. 367± 2. 120; 48 h, 12. 167 ± 1. 108), and ursolic acid significantly increased the expression level of miR-373-3p mimics in A549 cells transfected with miR-373-3p mimics (24 h, 16. 787±3. 109; 48 h, 16. 980±3. 106). mRNA for the target gene, TXNIP, (10. 757± 0. 79) and protein expression ( 0. 8210± 0. 043) predicted by miR-373-3p mimics were significantly increased. FCM result showed that miR-373-3p promoted apoptosis of A549 lung cancer cells ( 46. 20 ± 5. 970), and after being transfected with miR-373-3p mimics, the cells’ migration ability was significantly inhibited (P< 0. 001). Conclusions Ursolic acid can promote the apoptosis of A549 lung cancer cells and inhibit their migration. The mechanism may involve up-regulation of miR-373-3p expression.

Abstract: Objective In this study, we established a fluorescence quantitative PCR method for rapidly diagnosing a new type of goose-origin astrovirus (GoAstV). Methods After analyzing and comparing the whole-genome sequences of GoAstV downloaded from NCBI, a pair of specific primers and TaqMan probes were designed in its open reading frame-1a conservative region. By optimizing the reaction conditions, a standard curve was established, and the specificity, sensitivity and stability were verified. Results The minimum sample size was 1. 5×10² copies/ μL. The coefficients of variation for the intra-assay and inter-assay detection were < 0. 5% and 4%, respectively, with no specific amplification of other common waterfowl viruses. The clinical application result showed that the detection rate was significantly higher than that of conventional real-time PCR. Conclusions This fluorescence quantitative PCR method exhibited stronger specificity, higher sensitivity and better reproducibility for early detection and quantitative analysis of GoAstV.

Abstract: Objective To investigate the effect of cimetidine on intestinal epithelial integrity and the calmodulin- dependent protein kinase IV ( CaMKIV) / cyclic AMP ( cAMP ) response element modulator ( CREM ) pathway in necrotizing enterocolitis (NEC). Methods Rats were divided into a control group, model group, cimetidine group, and CaMKIV inhibitor group. Except for the control group, the NEC newborn rat model was established by hypoxia + reoxygenation + cold stimulation on the first day of birth in each group over 3 consecutive days. After daily cold stimulation, 30. 5 mg / kg cimetidine was injected intravenously in the cimetidine group. In the CaMKIV inhibitor group, 0. 72 mg / kg of the CaMKIV inhibitor, kn62, was administered by intubation, and the control group and model group were treated with normal saline for the same number of days. The rats were then observed clinically. Intestinal permeability was measured by the fluorescein isothiocyanate-dextran ( FITC-dextran) tracing method ; hematoxylin eosin ( HE) staining was used to observe the histopathological changes of the intestinal tract; the concentrations of platelet activating factor ( PAF) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA); and the protein levels of CaMKIV and CREM were detected by Western blot. Results In the model group, we observed decreased activity and slow responses, low appetite, and change of stool shape. The intestinal wall was thickened and edematous, with poor elasticity and some perforation, microscopically; the submucosa or lamina propria were markedly separated; villi were missing; and glands were disordered. Compared with the activity in the model group, activity in the cimetidine group and CaMKIV inhibitor group increased, and appetite was moderate; the intestinal wall was thickened and edematous, microscopically; and the submucosa or lamina propria were partially separated, with some partially denuded villi. Compared with the control group, the FITC-dextran levels, histological scores, and the levels of PAF, TNF-α, CaMKIV, and CREM proteins in the intestinal tissue of the model group mice were higher (P< 0. 05). Compared with the model group, the levels of FITC- dextran, histological scores, and the concentrations of PAF, TNF-α, and CaMKIV and CREM proteins in the intestinal tissue in the cimetidine group and CaMKIV inhibitor group were lower ( P< 0. 05). Conclusions Cimetidine may alleviate inflammation in NEC and improve the intestinal epithelium by inhibiting the CaMKIV/ CREM pathway, which may protect NEC newborn rats.

Abstract: Objective To investigate the protective effect of salidroside ( SDS) on type 2 diabetic osteoporosis (DOP) rats and its influence on the forkhead box transcription factor O1 (FoxO1) / β-catenin pathway. Methods The rat model of DOP was established by feeding rats a high glucose and high fat diet for 8 weeks, injecting the rats with 30 mg / kg streptozotocin (STZ) intraperitoneally after 8 weeks, and then resecting the ovaries under sterile conditions in the 10th week. After successful modeling, the rats were randomly divided into model group, SDS group, and FoxO1 agonist group, with eight rats in each group; the eight rats in the normal group were fed a normal diet for the same length of time as for the other groups. On the second day after establishing the model, the rats in the SDS group were given 36 mg / (kg·d) SDS by gavage, and the rats in the FoxO1 agonist group were given 40 mg / (kg·d) resveratrol (Res) by gavage, for 11 weeks. The fasting blood glucose concentration was measured using a glucometer. the morphology of the femur was evaluated by hematoxylin & eosin (HE) staining, and femoral bone mineral was measured by dual energy X-ray absorptiometry. the serum concentrations of reactive oxygen species (ROS), superoxide dismutase ( SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detecte by ROS, SOD, MDA kits, respectively; and the concentrations of FoxO1 and β-catenin proteins in the femur were detected by Western blot. Results After modeling and before administration, compared with the normal group, the fasting blood glucose concentration was higher in the model group, SDS group and FoxO1 agonist group (P< 0. 05). After administration, the bone trabeculae of rats in the model group showed obvious fracture, serious damage, and reduced number; the bone trabeculae of rats in the SDS group and FoxO1 agonist group showed obvious fracture, but the trabecular space was reduced, and the trabecular number was increased. Compared with the normal group, the fasting blood glucose and serum ROS and MDA concentrations were higher in the model group (P< 0. 05), while the femoral bone mineral density, serum SOD and GSH-Px concentrations, and FoxO1 and β-catenin concentrations in the femur were lower (P< 0. 05). Compared with the model group, the fasting blood glucose and serum ROS and MDA concentrations were lower in the SDS group and FoxO1 agonist group (P< 0. 05), while the femoral bone mineral density, and serum SOD and GSH-Px concentrations, and femoral FoxO1 and β-catenin concentrations in the femur were higher (P< 0. 05). Conclusions SDS can activate the FoxO1 / β-catenin pathway, enhance antioxidant stress, and protect DOP rats.

Abstract: Objective To observe changes in depressive-like behavior, and expression of oxidative stress markers and brain-derived neurotrophic factor (BDNF) in the CA1 hippocampus in post-stroke depression (PSD) model rats, and to investigate intervention with treadmill exercise in these rats and its possible mechanisms. Methods Forty-four male Sprague-Dawley rats were randomly divided into the following four groups: sham-operation, middle cerebral artery occlusion (MCAO), PSD, and PSD rats treated with 4 weeks of treadmill exercise only (PSD+E). Complete cerebral ischemic rat models of PSD were established by MCAO followed by 4 weeks of chronic unpredictable mild stimulation. Changes in rat behavior were evaluated by forced swimming test (FST) and sugar water preference test (SPT). The activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) in the hippocampus, were detected using kits. Immunohistochemical staining was used to detect BDNF expression in the CA1 hippocampus. Results Compared with the sham group, there was prolongation of the FST immobility time, while sucrose water intake and sucrose consumption ratio in the SPT were significantly decreased in the group. In the PSD group, there was reduced SOD and CAT activity, and increased MDA concentration, in the hippocampus, while the level of BDNF in the hippocampal CA1 of rats was significantly reduced compared with the group. Compared with the PSD group, the PSD + E rats had shorter FST immobility times, significantly higher sucrose water intake and sucrose consumption ratios in the SPT, enhanced SOD and CAT activity, decreased MDA concentration in the hippocampus, and significantly increased expression of BDNF in the hippocampal CA1. Conclusions Treadmill exercise alleviated depressive-like behavior and conferred neuroprotection by reinforcing antioxidant capability in the hippocampus and activating BDNF expression in the hippocampal CA1 of PSD model rats.

Abstract: Objective To detect changes in serum lipid levels due to serum uric acid-lowering therapy in spontaneously hypertensive rats with hyperuricemia. Methods Experimental rats were divided into five groups. The control group (A1; spontaneously hypertensive rats; 10 males, 10 females ) was administered the same volume of 0. 5% carboxymethyl cellulose sodium for 2 weeks. The spontaneously hypertensive rats with hyperuricemia group (B1; 15 males, 15 females) was administered adenine ( 150 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) and ethambutol (250 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) for 2 weeks. The control / continuing established animal model group (A2; spontaneously hypertensive rats; 5 males and 5 females randomly chosen from A1) received the same volume of 0. 5% carboxymethyl cellulose for 4 weeks. The spontaneously hypertensive rats with hyperuricemia / continuing established animal model group (B2; 5 males and 5 females randomly chosen from B1) were administered adenine (150 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) and ethambutol (250 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) for 5 weeks. The spontaneously hypertensive rats+hyperuricemia+serum uric acid-lowering therapy group (B3; 5 males and 5 females randomly chosen from B1) were administered adenine ( 150 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) and ethambutol ( 250 mg / kg dissolved in 0. 5% carboxymethyl cellulose sodium) and allopurinol (10 mg / kg Solved in 0. 5% Carboxymethyl cellulose-Na ) for 5 weeks. animal esperment in 2,4 and 7 weeks, before starting the experiment, the serum levels of uric acid, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol were tested using microplate readers. Results Serum uric acid levels and serum lipids in the experimental group differed significantly from those of the control group ( P<0. 05). Conclusions Serum uric acid-lowering therapy for spontaneously hypertensive rats with hyperuricemia altered the serum lipid levels.

Abstract: Objective To investigate the expressions of transforming growth factor-β1 ( TGF-β1), Clara cell secretory protein 16 (CC16), and type Ⅱ alveolar cell surface antigen 6 (Krebs Yon Denlungen-6; KL-6) in the lung tissue of bronchopulmonary dysplasia (BPD)-model rats and the relationship between the expressions of these proteins and lung cell apoptosis. Methods Newborn Sprague-Dawley rats were randomly divided into the control and model groups according to the random number table method . Rats in the model group were continuously exposed to 80% ~ 85% oxygen to construct the BPD model, and rats in the control group were always exposed to regular air. At 7, 14, and 21 days ( i.e., the 7 d model, 14 d model, and 21 d model groups), eight newborn rats were randomly selected and euthanized, and 5 mL of serum was retained. Hematoxylin and eosin staining was used to observe the lung histopathological changes in each group, and the radial alveolar count (RAC) and mean alveolar intercept were analyzed. TUNEL staining was used to detect apoptosis in the lung tissues of each group. Enzyme-linked immunosorbent assays were used to detect the TGF-β1, CC16 and KL-6 serum levels of newborn rats in each group. Western blot was used to detect the TGF-β1, CC16 and KL-6 expression levels in the lung tissue of each group. The relationships between the TGF-β1, CC16 and KL-6 expressions and the apoptosis rates in the lung tissue were analyzed. Results Compared with that of the normal group, the BPD injury to the lung tissue in the model group increased as the 80% ~ 85% oxygen exposure was prolonged. The serum levels of RAC and CC16 and the CC16 expression in the lung tissue were significantly reduced. At the serum level, the TGF-β1 and KL-6 expressions in the lung tissue were increased significantly (P<0. 05). Correlation analysis showed that the TGF-β1 and KL- 6 expressions in the lung tissue of the neonatal rats in the model group were positively correlated with the apoptosis rate in the lung tissue (r= 0. 977, 0. 970, P= 0. 000), and CC16 expression was correlated with apoptosis. The mortality rate showed a negative correlation ( r= - 0. 982, P= 0. 000). Conclusions TGF-β1, CC16, and KL-6 expression in lung tissue was closely correlated with apoptosis in the lung tissues of BPD-model rats.

Abstract: Objective To study the effects and mechanism of microRNA (miR) -572 on the proliferation and apoptosis of gastric cancer cells. Methods Differences in miR-572 expression between gastric cancer cells and normal gastric mucosal cells was detected by Real-time PCR. NCI-N87 cells transfected with the miR-572 inhibitor were examined using the following techniques: MTT assay of cell proliferation, propidium iodide ( PI) single staining to determine cell cycle distribution, annexin V-fluorescein isothiocyanate / PI to measure apoptosis, and Western blot to detect the expression of cyclin-dependent kinase 4 ( CDK4), p21, B-cell lymphoma / leukemia - 2 ( Bcl-2), and Bcl-2-associated X protein (Bax). An online target gene prediction software identified the gene encoding WW domain-containing oxidoreductase (WWOX) as a possible target of miR-572. This relationship was tested using a luciferase reporter system in which WWOX small interfering RNA ( siRNA) and the miR-572 inhibitor were cotransfected into gastric cancer cells, followed by measurement of cell proliferation, cell cycle distribution and apoptosis as above. Results The expression level of miR-572 in gastric cancer cells was significantly higher than that in normal gastric mucosal cells. Gastric cancer cells transfected with the miR-572 inhibitor showed decreased proliferation, an increased proportion of G1 phase, an increased apoptosis rate, decreased expression of CDK4 and Bcl-2, and increased expression of p21 and Bax protein.,m iR-572 negatively regulated the expression of WWOX protein. WWOX siRNA reversed the inhibitory effect of the miR-572 inhibitor on proliferation, cell cycle arrest and apoptosis of gastric cancer cells. Conclusions Downregulation of miR-572-mediated negative regulation of WWOX inhibited the proliferation of gastric cancer cells, blocked the cell cycle and induced apoptosis.

Abstract: Objective To investigate the effect of miR-377-5p on angiogenesis and lymphangiogenesis in colon cancer by downregulating vascular endothelial growth factor (VEGF)-C. Methods Subjects were divided into the miR- 377-5p interference, miR-377-5p negative control and miR -377-5p overexpression groups. Real-time fluorescence RT- PCR, Western blot, CCK-8, flow cytometry, cell scratches, Transwell assays, and angiogenesis experiments were used to detect miR-377-5p mRNA and protein expression, cell proliferation, apoptosis, migration, invasion, angiogenesis and lymphangiogenesis. Results miR-377-5p mRNA and protein expressions in the colon cancer tissue were significantly lower than those in the normal colon tissue ( both P< 0. 05). Compared with those of the miR-377-5p interference group, the mRNA and protein expressions in the miR-377-5p negative control and overexpression groups were significantly increased (both P< 0. 05). Compared with the miR-377-5p negative control group, miR-377-5p overexpression colon cancer cell proliferation in the miR-377-5p negative control and miR-377-5p overexpression groups was significantly reduced compared with that of the miR-377-5p interference group (P<0. 05). Colon cancer cell proliferation in the miR-377-5p overexpression group was significantly reduced compared with that of the miR-377-5p negative control group (P<0. 05). Colon cancer cell proliferation and apoptosis in the miR-377-5p negative control and overexpression groups were significantly increased compared with those of the miR-377-5p interference group (P<0. 05). The apoptotic ability of the colon cancer cells in the miR-377-5p overexpression group was significantly increased compared with that of the miR-377-5p negative control group (P<0.05 ). The wound-healing tests showed that the migration ability of colon cancer cells in the miR-377-5p overexpression group was significantly lower than that of the miR-377-5p interference and miR-377-5p negative control groups (P<0. 05). Colon cancer cells in the miR-377-5p overexpression group were also significantly less invasive than those of the miR-377-5p interference and negative control groups (P<0. 05). VEGF-A, VEGF-C, P-Akt, and VEGFR-3 protein levels were significantly lower in the miR-377-5p overexpression group than in the miR-377-5p interference and miR-377-5p negative control groups (P<0. 05). Microvessel density and lymphatic microvessel density were significantly lower in the miR-377-5p overexpression group than in the miR-377-5p interference and miR-377-5p negative control groups (P<0. 05). Conclusions Low miR-377-5p expression inhibited colon cancer cell proliferation, migration and invasion; promoted colon cancer cell apoptosis; and inhibited blood vessels and lymph in the tumor by directly targeting VEGF-C tube generation.

Abstract: Objective We investigated the effects of recombinant human erythropoietin (rhEPO) on inflammatory factors and mitochondrial damage in the brain tissue of rats with traumatic brain injury. Methods Sprague-Dawley rats were randomly divided into three groups, 15 in each group: a sham operation group (sham group), a model group, and a rhEPO intervention group ( treatment group). The rats in the model group and the treatment group were subjected to a modified Feeney weight-drop model, in which the head strike establishes the traumatic rat model; the sham group was not subjected to this head strike. At the end of modeling, the treatment group was intraperitoneally injected with rhEPO at a dose of 5 000 IU/ kg daily. The sham group and the model group were intraperitoneally injected with an equal amount of normal saline. The rats were sacrificed seven days after continuous administration. rhodamine 123(Rh123) staining was used to detect changes in mitochondrial membrane potential. Immunohistochemistry was used to detect the expression of interleukin-1β(IL-1β), interleukin-6( IL-6), and tumor necrosis factor-α( TNF-α) in the brain tissue of each group. Western blot analysis was used to detect the protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission 1 protein ( Fis1), mitochondrial fusion protein 2 ( Mfn2), and optic atrophic protein 1 ( Opa1). Results Compared with the sham group, the Rh123 fluorescence intensity of brain tissue cells in the model group was significantly weakened, the expressions of IL-1β, IL-6, TNF-α, Drp1, and Fis1 proteins were significantly increased, and the expressions of MFN2 and OPA1 proteins were significantly decreased (all P< 0. 05). Compared with the model group, the Rh123 fluorescence intensity of brain tissue cells in the treatment group was significantly increased, the expressions of IL- 1β, IL-6, TNF-α, Drp1, Fis1 proteins were significantly decreased, and the expressions of Mfn2 and OPA1 proteins were significantly increased (all P< 0. 05). Conclusions Recombinant human erythropoietin can reduce inflammatory response and mitochondrial damage after traumatic brain injury, thereby playing a protective role in brain tissue after traumatic brain injury.

Abstract:Air distribution is an important factor affecting the flow field of a laboratory animal room in a barrier environment. We studied a mouse breeding room in a barrier environment as an example, using Airpak software to simulate the effect of the position, number and size of exhaust outlets, as well as the cage position, on the indoor flow field. The simulation result showed that the number and location of exhaust outlets mainly affected the local air distribution, and had little effect on the average temperature, air speed, air age and mean square deviation of the entire mouse feeding room. The average age of air particles in cages arranged along the width direction of the room was 25 s shorter than that in cages arranged along the length direction of the room. Additionally, there was a linear function relationship between the fresh air cooling load index during summer air conditioning and the number of air changes, with the fresh air cooling load accounting for 92. 25% of the total cooling load. Compared with the open cage system, the fresh air cooling load index of the independent ventilation cage system was reduced by 62. 6%.

Abstract:Long non-coding RNA ( lncRNA) is RNA that is >200 bp long and regulates gene expression at the transcriptional, post-transcriptional and translational levels. Dysfunction of lncRNA is closely related to the pathological processes of many diseases, including nervous system diseases. Autophagy is a lysosome-dependent degradation pathway in eukaryotic cells that plays an important role in cell growth, development, senescence and maintenance of intracellular homeostasis. Recent studies have confirmed that lncRNA plays an important role in the occurrence and development of nervous system diseases, and regulation of autophagy by lncRNA is an important topic; however, the specific mechanisms of this regulation remain unclear. This paper reviews the molecular mechanisms of lncRNA regulation in autophagy and its related research progress concerning nervous system diseases to provide a theoretical and experimental basis for further studying the pathogenesis and drug treatment strategies of nervous system diseases.

Abstract:Alzheimer’ s disease is an irreversible and progressive neurodegenerative disease. Its pathogenesis is complicated, and its pathological changes mainly involve β-amyloid protein deposition, Tau protein hyperphosphorylation, neuroinflammation and synaptic abnormalities. The matrix metalloproteinase family can alter the pathological process of Alzheimer’s disease by influencing β-amyloid metabolism, participating in the formation of Tau oligomers, disrupting brain barrier function, promoting neuroinflammation, and influencing synaptic plasticity. To provide a theoretical basis for matrix metalloproteinases as potential therapeutic targets for Alzheimer’ s disease, we reviewed the existing research on matrix metalloproteinases and Alzheimer’s disease.

Abstract:Ischemic stroke is still a heavy burden due to its higher incidence and mortality rate. Therapeutic hypothermia is considered as the most promising treatment for ischemic stroke. However, there is still an uncertain efficacy in clinical trials despite evidence of efficacy in pre-clinical experiments. Nonhuman primates serve as the bridge between pre-clinical and clinical studies. We summarize recent progress of therapeutic hypothermia in stroke models of nonhuman primates. We want to promote the translation of therapeutic hypothermia in clinical trials.

Abstract:Epilepsy is a common neurological disorder, with but little acknowledge ofis known about its causes, thus leading tomaking it difficulty into finding an effective therapyies. Over the last 30 years, experimental models of epilepsiesy have contributed greatly in to improving our understanding of epilepsy and identification of potential therapeutic agents for epilepsy. However,there is notno one “ideal” animal model exists for the discoverying of new antiepileptic drugs and or fully explaining epileptogenesis. This paper provides a review of the research of using experimental models of epilepsiesy and provides new some insights on the futureand direction of for the establishment ofing epileptic models of epilepsy.

Abstract:Knee osteoarthritis can be divided into primary and secondary types, but the etiology of these types is unknown. Animal experiments enable further exploring the pathogenesis and prevention of knee osteoarthritis. The related literature suggests that classic models can be divided into artificial induction and spontaneous modeling. The associated mainstream traditional Chinese medicine syndromes for this disease are kidney yang deficiency, blood stasis and cold dampness syndrome, which correspond to three modeling method . Animal models that combine these diseases and syndromes will be important for future research. These models, combined with the author’s practical experience in multiple modeling method , provide a review for reference.

Abstract:CXXC zinc finger protein-1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. Studies have shown that the disorder of CFP1 affects gene expression, DNA damage repair, signal transduction, proliferation, division and differentiation of cells, and is closely related to the occurrence, development, treatment and poor prognosis of malignant tumors. This paper provides a brief review of the basic function of CFP1 and research progress on its role in malignant tumors to provide the basis for follow-up research on new tumor markers and potential therapeutic targets.