Abstract: Objective To establish a stable rat model of hyperuricemia. Methods By administering potassium oxonate alone or in combination with fructose or hypoxanthine, a hyperuricemia model was established with different administration times using various modeling method . The levels of serum uric acid, creatinine, urea nitrogen, xanthine oxidase (XO), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activity of hyperuricemia rats were measured. Pathological changes in the liver and kidney were observed. Protein expression of ATP-binding cassette subfamily G member 2 (ABCG2) were analyzed. Results Compared with the normal group, the levels of the serum uric acid, urea nitrogen, AST, and XO activity in rats administered potassium oxonate alone for 7 days were increased significantly (P< 0. 05), while the liver and kidney were slightly injured and kidney ABCG2 protein expression was decreased significantly (P<0. 05). Compared with the normal group, the level of serum uric acid in rats was increased significantly (P<0. 05), whereas the levels of creatinine, urea nitrogen, AST, ALT, and XO activity and kidney ABCG2 protein expression showed no significant changes (P>0. 05) in the group with 7 day of combined potassium oxonate and fructose administration. The levels of serum uric acid, urea nitrogen, and XO activity were increased significantly (P<0. 05) and the levels of AST and ALT activity showed no significant changes ( P> 0. 05) in the group with 14 days of potassium oxonate and fructose administration. There were no significant morphological changes in the liver and kidney of rats. Compared with the normal group, the levels of serum uric acid, creatinine, urea nitrogen, and AST, ALT, XO activity in rats with 7 days of potassium oxonate and hypoxanthine administration were increased significantly ( P< 0. 05 ). Kidney ABCG2 protein expression was decreased significantly (P< 0. 05) and the damage of the liver and kidneys was severe. Conclusions Potassium oxonate alone was suitable to establish a rat model of acute hyperuricemia with mild hepatic and renal injuries. Fructose combined with potassium oxonate may successfully establish a chronic hyperuricemia rat model with no significant effects on the liver or kidneys. Hypoxanthine combined with potassium oxonate successfully established an acute hyperuricemia rat model with severe hepatic and renal injuries.

Abstract: Objective To explore the effect of acupuncture on the dendritic structure of the hippocampal CA1 area and cognitive functions in Alzheimer’ s disease mice. Methods Twenty-four male rapidly aging SAMP8 mice were randomly divided into model and acupuncture groups with 12 mice each. Another 12 male normal aging SAMR1 mice were used as the control ( control group). Mice in control and model groups were untreated. Mice in the acupuncture group received acupuncture treatment for 8 weeks ( once every other day). The acupuncture sites were Baihui, Shenshu, and Taixi. A Morris water maze test was sued to assess mouse cognitive functions. After collecting the mouse hippocampal CA1 area, Golgi staining was used to observe the structure of pyramidal cell dendrites. Immunohistochemical staining was used to detect expression of Aβ_1-40 and Tau. Western blot was used to measure BDNF, SYN, and MAP2 protein expression levels. Results (1) Compared with the control group, the model group had a higher escape latency on the 5^th day of water maze training, while the number of cross-platforms was lower (P<0. 05). Compared with the model group, the acupuncture group had a lower escape latency on the 5^th day of water maze training, and a higher number of cross-platforms (P<0. 05). (2) Compared with the control group, the lengths of basal and apical dendrites, and the numbers of basal dendrites and branches of apical dendrites were all lower in the model group (P< 0. 05). Compared with the model group, the above indicators were all higher in the acupuncture group (P<0. 05). (3) Compared with the control group, the average optical density of Aβ_1-40 and Tau expression was higher in the model group (P<0. 05). Compared with the model group, the above indicators were lower in the acupuncture group ( P<0. 05). (4) Compared with the control group, the protein expression levels of BDNF, SYN, and MAP2 were lower in the model group (P<0. 05). Compared with the model group, the above indexes were higher in the acupuncture group (P<0. 05). Conclusions Acupuncture at Baihui, Shenshu and Taixi might improve the cognitive function of rapidly aging SAMP8 mice by activating BDNF/ SYN/ MAP2 signaling pathway and improving the length and number of dendritic branches in the CA1 region of hippocampus.

Abstract: Objective To provide a reference for basic experiments by studying and comparing the characteristics of body temperature changes in rabbit fever models induced by injection of various concentrations of dry yeast and lipopolysaccharide. Methods Thirty 2-month-old male New Zealand rabbits were randomly divided into five groups: a normal group, two groups injected with 10% or 20% dry yeast suspension, and two groups injected with 0. 2 or 0. 5 μg / mL lipopolysaccharide solution with six rabbits in each group. The anal temperature of dry yeast groups was monitored every hour for 26 h before and after modeling, and that of lipopolysaccharide groups was monitored every 20 min for 6 h before and after modeling. The changes in body temperature and other symptoms were recorded, an average body temperature curve was drawn, changes in body temperature at each time point were calculated, and the trends of the body temperature change in each group were compared. Results Two hours after the dry yeast suspension was injected subcutaneously, body temperature decreased to lower than the basal body temperature. However, body temperature began to rise in 2 ~ 4 h, reached its peak in 6~ 8 h, then leveled off for at least 20 h. With the increase in concentration, the temperature rise was increased and the peak occurred later. Lipopolysaccharide was injected intravenously at the ear margin and fever began in 40 min. The body temperature curve showed biphasic or triphasic heat and reached the first peak in 60 ~ 80 min and then leveled off for 240~ 300 min. The temperature rise had no obvious relationship with the injection dose of lipopolysaccharide, but the fever duration was increased with the increase in dose. Conclusions Dry yeast and lipopolysaccharide are reliable agents to induce fever in rabbits. The dry yeast model is a long-term high fever model, while the lipopolysaccharide model has a short fever time. The appropriate model to induce fever should be selected in accordance with the experimental requirements .

Abstract: Objective To explore the effect of low expression of circular RNA homeodomain- interactingproteinkinases 3 (circHIPK3) on the apoptosis of hippocampal neurons induced by Amyloid β-protein (Aβ). Methods Bioinformatics software prediction and double luciferase reporter gene experiments were used to investigate the targeting relationships between microRNA-124 (miR-124) with HIPK3 and signal transduction and activator of transcription 3 (STAT3). Primary hippocampal neurons were cultured in vitro and divided into the control group (normal cultured), the amyloid β-protein ( Aβ) group ( Aβ stimulation), the Aβ + siSTAT3-NC group ( Aβ stimulation after transfection of siSTAT3-NC), the Aβ+siHIPK3 group (Aβ stimulation after transfection of siHIPK3), the Aβ+siHIPK3+antimiR-NC group (Aβ stimulation after cotransfection of siHIPK3 and inhibitor-NC), the Aβ + siHIPK3 + antimiR-124 group ( Aβ stimulation after cotransfection of siHIPK3 and miR-124 inhibitor), the Aβ+siHIPK3+antimiR-124+siSTAT3-NC group (Aβ stimulation after cotransfection of siHIPK3, miR-124 inhibitor and siSTAT3-NC) and the Aβ+siHIPK3+antimiR-124 +siSTAT3 group (Aβ stimulation after cotransfection of siHIPK3, miR-124 inhibitor and siSTAT3). The expression levels of HIPK3 and miR-124 were detected by real-time fluorescence quantitative PCR ( qRT-PCR), and expression level of STAT3 protein was detected by Western blot. Survival and apoptosis rates of hippocampal neurons were measured by the thiazole blue ( MTT) method and flow cytometry, respectively. Caspase-3 activity was detected by Cysteine-containing aspartate proteolytic enzyme 3 (Caspase-3) activity detection kit. Results Bioinformatics and double luciferase reporter gene experiments showed that HIPK3 targeted miR-124. Bioinformatics, double luciferase reporter gene experiments and Western blot demonstrated that miR-124 targeted STAT3 protein expression. Compared with the control group, expression levels of HIPK3 and STAT3 protein, and the apoptosis rate and caspase-3 activity in hippocampal neurons were significantly higher in the Aβ group, whereas the survival rate of neurons and expression level of miR-124 were significantly lower (P< 0. 05). Compared with those in the Aβ+siSTAT3-NC group, the above indexes were significantly reversed in the Aβ+ siHIPK3 group ( P< 0. 05). Compared with those in Aβ + siHIPK3 + antimiR-NC group, the above indexes showed significant changes in the Aβ+siHIPK3+antimiR-124 group (P< 0. 05), and the trend was opposite to those in the Aβ+ siHIPK3 group. Compared with the Aβ+siHIPK3 +antimiR-124 +siSTAT3-NC group, the indexes of the Aβ+siHIPK3 + antimiR-124+siSTAT3 group were markedly changed (P< 0. 05), and the trend was opposite to those of the Aβ+siHIPK3 +antimiR-124 group. There were no significant differences between the Aβ and Aβ+siHIPK3-NC groups, the Aβ+siHIPK3 and Aβ+siHIPK3+antimiR-NC groups, or the Aβ+siHIPK3+antimiR-124+siSTAT3-NC and Aβ+siHIPK3+antimiR-124+ siSTAT3 groups. Conclusions The low expression of circHIPK3 can inhibit apoptosis of hippocampal neurons induced by Aβ, and its mechanism is related to regulation of the miR-124 / STAT3 axis.

Abstract: Objective Observe the effect of microRNA-574-3p (miR-574-3p) on the proliferation of colon cancer cells, and explore its potential mechanism. Methods HCT116 colon cancer cells were transfected with miR-574-3p mimics or a negative control and used miR-574-3p mimics and negative control groups, respectively. Normal HCT116 cells were used as the blank control group. RT-qPCR was used to detect expression of miR-574-3p. CCK-8 assays were used to measure cell proliferation. Colony formation assay was used to assess cell clone formation. Flow cytometry was used to detect cell cycle changes. Western blot was used to detect expression of Cyclin A1, CDK2, PCNA, Cdc25A, and p53 proteins. Results Compared with the negative control group, expression of miR-574-3p in the miR-574-3p mimics group was upregulated significantly (P<0. 01), and cell viability was significantly reduced at 36 ~ 72 h (P<0. 01). Compared with the negative control group, the colony formation rate was significantly reduced in the miR-574-3p mimics group (P<0. 01), while the proportion of S-phase cells was increased significantly (P< 0. 01). Compared with the negative control group, expression of Cyclin A1, CDK2, PCNA, and Cdc25A was significantly downregulated in the miR-574-3p mimic group (P< 0. 01) and expression of p53 protein was upregulated significantly (P<0. 01). There was no significant difference in the above indicators between negative control and blank control groups. Conclusions MiR-574-3p inhibits the proliferation of HCT116 colon cancer cells, which may be related to the downregulation of Cyclin A1, CDK2, PCNA, and Cdc25A and the upregulation of p53 protein expression, which ultimately induces cell cycle arrest in S phase.

Abstract: Objective To investigate the expression of miR-122 in the kidneys of diabetic nephropathy (DN) mice and the effect of miR-122 in the kidney of DN mice. Methods Streptozotocin ( STZ) intraperitoneal injection combined with a high-sugar and high-fat diet was used to establish the DN C57BL/ 6 mouse model. Thirty DN mice were randomly divided into the model group, antagomir-NC group and antagomir-122 group (10 / group). In addition, 10 healthy C57BL/ 6 mice without any treatment were selected as a normal control group. After the successful establishment of the model, the antagomir-122 and antagomir-NC groups were given tail vein injections of antagmir-122 and antagomir-NC every 7 days, and the model and normal control groups were given tail vein injections of the same volume of normal saline. After 8 weeks, serum and urine samples were collected and mice were sacrificed to obtain kidney specimens. An automatic biochemical analyzer was used to detect serum creatinine (Cr), blood urea nitrogen (BUN) and 24 h urine protein levels. Periodic acid schiff staining was used to evaluate renal histopathological changes, qRT-PCR was used to detect expression levels of miR-122 in renal tissue, and a kit was used to detect levels of glutathione peroxidase ( GSH-Px ), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissues. Western blot was used to detect protein levels of Sirtuin 1 ( Sirt1), α-smooth muscle actin (α-SMA), and fibronectin in renal tissue. Results Compared with the normal control group, the glomerulosclerosis score of mice increased (P<0. 05), the expression of miR-122, α-SMA and fibronectin protein in renal tissue increased (P<0. 05), circulating levels of Cr and BUN, and quantitative levels of 24 h urine protein and MDA levels in renal tissue were all significantly increased (P<0. 05), and the expression levels of Sirt1 protein, and SOD and GSH-Px levels in renal tissue were all significantly reduced (P<0. 05) in the model group. There were no significant differences in the endpoints examined between the model group and antagomir-NC group. Compared with the antagomir-NC group, the glomerulosclerosis score, miR-122 expression, renal α-SMA and fibronectin protein levels, Cr and BUN levels, and 24 h urinary protein and renal tissue MDA levels were significantly decreased (P<0. 05), and renal tissue GSH-Px, SOD, and Sirt1 protein expression levels were significantly increased (P<0. 05) in the antagomir-122 group. Conclusions The expression of miR-122 was increased in kidneys of DN mice. Silencing miR-122 can protect renal tissues of DN mice from anti-oxidative stress and fibrosis, and its mechanism may be related to the regulation of Sirt1.

Abstract: Objective To study the inhibitory effects of gentiopicroside on tumor growth and anti-angiogenesis in mice with H₂₂ hepatocellular carcinoma. Methods A H₂₂ hepatocellular carcinoma mouse model was established by subcutaneous injection of a H₂₂ cell suspension into the right axilla. Mice with H₂₂ hepatocellular carcinoma were randomly divided into a model group, low and high dose gentiopicroside groups ( 50 and 100 mg / kg, respectively ), and a cyclophosphamide group (20 mg / kg) with 10 mice in each group. Another 10 healthy mice were used as the normal group. After 14 days of administration, body weight, tumor weight, tumor inhibition rate, thymus index, spleen index, serum IFN-γ and IL-2 contents, and expression levels of bFGF, TGF-β, VEGF, p-PI3K, and p-Akt were measured in tumor tissues. Results Compared with the H₂₂ hepatocellular carcinoma model group, the body weights of mice in low and high dose groups of gentiopicroside did not change significantly (P>0. 05), while the tumor weight was reduced significantly (P<0. 01),with the tumor inhibition rates of 30. 43% and 42. 93%, respectively. Compared with the H₂₂ hepatocellular carcinoma model group, the thymus index, spleen index, and serum IFN-γ and IL-2 contents of mice in low and high dose gentiopicroside groups were increased significantly (P<0. 05 or P<0. 01), while expression of bFGF, TGF-β, VEGF, p-PI3K, and p-Akt in tumor tissues was decreased significantly (P<0. 05 or P<0. 01). Conclusions Gentiopicroside has an inhibitory effect on tumor growth and anti-angiogenesis effect in H₂₂ hepatocellular carcinoma mice, which is related to improving immunity, increasing serum IFN-γ and IL-2 levels, and inhibition of activation of the PI3K/ Akt signaling pathway.

Abstract: Objective To explore the effect of Xiaoxianxiong Decoction on vascular endothelial injury in mice with hyperlipidemia ( Hyperlipemia, HLP). Methods Thirty-six C57BL/ 6 mice were randomly divided into control, model, low dose group (0. 03 g / mL Xiaoxianxiong Decoction), medium dose (0. 06 g / mL Xiaoxianxiong Decoction), high dose group (0. 12 g / mL Xiaoxianxiong Decoction), and Lovastatin (2. 5 mg / kg lovastatin) groups. Six rats in each group were fed a high fat diet for 8 weeks to establish the HLP model and administered corresponding drugs for treatment. During the administration period, the general behavioral state of mice in each group was observed and mice were weighed once a week. HE staining was used to observe histopathological changes of aortic vessels. Immunohistochemistry was used to detect expression of von Willebrand factor ( vWF) in aortic tissues of mice. qRT-PCR was used to measure mRNA levels of vascular endothelial growth factor (VEGF), EPH receptor B4 (EphB4), and Ephrin-B2 (EphrinB2) in aortic tissues of mice. Western blot was used to measure the protein levels of VEGF, EphB4, and EphrinB2 in aortic tissues of mice. Results Compared with the control group, the activity and food intake of mice in the model group was decreased, hair was poor, weight had increased, and the expression levels of vWF, VEGF, EphB4, and EphrinB2 were increased in aortic tissue. Compared with the model group, the activity and food intake of mice in each dose group of Xiaoxianxiong Decoction and the Lovastatin group were increased, hair was brighter, weight was reduced, and the expression levels of vWF, VEGF, EphB4, and EphrinB2 were decreased in aortic tissue (P< 0. 05). Compared with the low dose group, mRNA and protein expression levels of VEGF, EphB4, and EphrinB2 were decreased in medium and high dose groups ( P< 0. 05). Conclusions Xiaoxuai decoction inhibits the development of HLP and protects the vascular endothelium of mice.

Abstract: Objective To observe the effects of different animal breeds and modeling method on animal models of melasma, and provide ideas for the successful preparation of animal models exhibiting the clinical features of melasma. Methods Animal models of melasma were prepared using SD rats, and KM and C57BL/ 6 mice. The SD rats were randomly divided into a normal group and high, medium and low dose progesterone groups ( 25, 15 and 7. 5 mg / kg, respectively). KM mice were randomly divided into a normal group, and high-dose and low-dose progesterone groups (30 and 20 mg / kg, respectively). Animals in the treated groups were injected with progesterone in the main muscle of the hind leg. Animals in the normal group were injected with the same volume of normal saline at the same site as the high-dose group for 30 consecutive days. In addition, C57BL/ 6 mice were randomly divided into normal, ultraviolet-progesterone model and ultraviolet model groups. In the ultraviolet-progesterone group, 20 mg / kg progesterone was injected into the main muscle of the hind leg once a day, and ultraviolet light was given once every two days. The ultraviolet group received intramuscular injections of normal saline at the same volume and frequency and with similar ultraviolet irradiation treatment, while the normal group received the same volume of normal saline without ultraviolet treatment for 21 consecutive days. After treatment, local skin tissue samples from each group were taken for hematoxylin-eosin and Masson-Fontana staining, and changes to melanin particles were observed under light microscopy. Results Compared with the normal groups, no significant changes in melanin were observed in the SD rats and KM mice, while significantly more melanin particles was observed in C57BL/ 6 mice. Conclusions The typical clinical manifestations of chloasma are difficult to simulate by progesterone treatment alone in albino rodents, such as SD rats and KM mice. C57BL/ 6 mice provide a relatively reliable animal strain for the establishment of melasma models. Animal melasma models using C57BL/ 6 mice can be successfully established by means of ultraviolet exposure combined with or without progesterone treatment.

Abstract: Objective To investigate the mechanism of aloe emodin (AE) in promoting autophagy by regulating miR-30b expression in endometrial carcinoma cell line HEC-1-B. Methods The expression level of miR-30b in normal endometrial cells and endometrial cancer cell lines HEC-1-A, HEC-1-B, and RL95 - 2 was measured by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). HEC-1-B cancer cells with the highest expression level of miR-30b were divided into a HEC-1-B cancer cell group, miR-30b inhibitor NC group (transfected with miR-30b inhibitor NC), miR-30b inhibitor group (transfected with miR-30b inhibitor), AE group (30 μmol / L AE, untransfected), AE+ transfection group: AE+miR-30b mimics NC group ( 30 μmol / L AE, transfected with miR-30b mimics NC), and AE+ miR-30b mimics group ( 30 μmol / L AE, transfected with miR-30b mimics). The expression level of miR-30b, cell proliferation, apoptosis rate, and autophagy rate were determined by qRT-PCR, CCK-8 assays, flow cytometry, and monodansulfonyl cadaverine fluorescence staining respectively. Western blot was used to measure the protein expression levels of Beclin 1, LC3-I, LC3-II, and p62. Results Compared with normal human endometrial epithelial cells, expression levels of miR-30b were significantly higher in HEC-1-A, HEC-1-B, and RL95-2 cancer cells (P< 0. 05). The expression level of miR-30b was the highest in HEC-1-B cancer cells. Thus, HEC-1-B cancer cells were selected for transfection experiments. Compared with HEC-1-B cancer cell and miR-30b inhibitor NC groups, the miR-30b inhibitor group had a significantly lower miR-30b expression level, cell proliferation rate, and p62 protein expression level (P< 0. 05), and significantly higher apoptosis rate, autophagy rate, Beclin 1 protein expression level, and LC3-II/ I ratio (P< 0. 05). Compared with the HEC-1-B group, AE and AE+miR-30b mimics NC groups had significantly lower miR-30b expression levels, cell proliferation rates and p62 protein expression levels ( P< 0. 05), and a significantly higher apoptosis rate, autophagy rate, Beclin 1 protein expression level, and LC3-II/ I ratio (P< 0. 05). Compared with the AE+ miR-30b mimics NC group, the AE + miR-30b mimics group had a significantly higher miR-30b expression level, cell proliferation rate, and p62 protein expression level (P< 0. 05), and significantly lower apoptosis rate, autophagy rate, Beclin 1 protein expression level, and LC3-II/ I ratio ( P< 0. 05). Conclusions Expression of miR-30b is high in endometrial carcinoma cells. AE may inhibit the expression of miR-30b, promote autophagy and apoptosis of cancer cells, and inhibit the proliferation of cancer cells. Overexpression of miR-30b reverses the effect of AE.

Abstract: Objective To investigate the effect and mechanism of miR-16-5p on pyrolysis of rat normal liver cell line BRL-3A induced by hypoxia-reoxygenation. Methods An in vitro model of hepatic ischemia reperfusion injury was established by cellular hypoxia-reoxygenation and the pyrolysis rate was measured by flow cytometry. RT-qPCR was used to measure the expression level of miR-16-5p. Overexpressed miR-16-5p in cells by miR-16-5p mimics was used to examine the effect of miR-16-5p on pyrolysis. Western blot was used to measure protein expression levels of pyrolysis-related proteins caspase 1, IL-1β, and IL-18. The relationship between miR-16-5p and NLRP1 was predicted through bioinformatics analysis and dual luciferase reporter gene assays. Interference and overexpression of NLRP1 were performed to investigate the effect of NLRP1 and the miR-16-5p / NLRP1 axis on pyrolysis. Results Compared with the blank control group, the pyrolysis rate of the model group was increased significantly ( P< 0. 01) and expression of miR-16-5p was decreased significantly (P<0. 05). Overexpression of miR-16-5p significantly decreased the pyrolysis rate (P<0. 01) and inhibited the expression of caspase 1, IL-1β, and IL-18 (P<0. 01 or P<0. 05). The dual luciferase reporter gene assay showed that NLRP1 was a target gene of miR-16-5p. Overexpression of miR-16-5p significantly reduced the mRNA and protein levels of NLRP1 (P< 0. 01 or P< 0. 05). Additionally, overexpression of NLRP1 reversed the inhibitory effect of miR-16-5p on pyrolysis (P<0. 01) and the inhibitory effect on the expression of caspase 1, IL-1β, and IL-18 (P<0. 01 or P<0. 05). Conclusions MiR-16- 5p inhibits expression of caspase 1, IL-1β, and IL-18 by targeting NLRP1, thereby improving pyrolysis of BRL-3A cells caused by hypoxia-reoxygenation.

Abstract: Objective To investigate the protective effect of dexmedetomidine preconditioning on ischemia- reperfusion injury ( MIRI) in isolated rat hearts and its potential regulatory mechanism via the connexin 43 ( Cx43) / mitochondrial ATP-sensitive potassium channel ( mito-KATP) signaling axis. Methods The isolated heart Langendorff perfusion model was used. The random number table method was used to divide 50 isolated hearts into 5 groups (n= 10 / group): control ( Blank group ), ischemia-reperfusion ( I/ R group ), ischemia-reperfusion + dexmedetomidine preconditioning (I/ R+Dex group), ischemia-reperfusion+dexmedetomidine preconditioning+mito-KATP channel blocker 5- HD (I/ R+Dex+5-HD group), and ischemia-reperfusion+mito-KATP channel blocker (I/ R+5-HD group) groups. The rat model of isolated myocardial ischemia-reperfusion injury was prepared by stopping perfusion for 30 min and reperfusion for 120 min. The Blank group was continuously perfused with K-Hsolution for 180 min. The I/ R group was perfused with KH solution for 30 min, stopped for 30 min, and then perfused with KH solution for 120 min, causing MIRI injury. The I/ R+ Dex group was perfused with KH solution containing 10 mg / L dexmedetomidine for 30 min , stopped for 30 min, and then perfused with KH solution for 120 min. The I/ R+Dex+5-HD group was perfused with KH solution containing 10 mg / L of mito-KATP channel blocker 5-hydroxykulanic acid (5-HD) for 15 min, perfused with KH solution containing 10 mg / L of dexmedetomidine for 15 min, stopped for 30 min, and then perfused with KH solution for 120 min. The I/ R+5-HD group was perfused with KH solution containing 10 mg / L of 5-HD for 30 min, stopped for 30 min, and then perfused with KH solution for 120 min. Triphenyltetrazolium chloride staining was used to detect the proportion of cardiac infarction in each group. The expression of Cx43 in rat hearts from each group was detected by immunohistochemistry. Western blot was used to detect the heart expression levels of p-Cx43 in each group. Results Compared with the Blank group, the myocardial infarction area of the I/ R, I/ R +Dex, I/ R +Dex + 5-HD and I/ R + 5-HD groups were significantly increased, and the expression levels of Cx43 and p-Cx43 were significantly decreased. Compared with the I/ R group, the area of myocardial infarction in the I/ R+Dex and I/ R+Dex+5-HD groups were significantly reduced, and the expression levels of Cx43 and p- Cx43 were increased. Compared with the I/ R group, the area of myocardial infarction in the I/ R + 5-HD group was significantly increased, and the expression levels of Cx43 and p-Cx43 were significantly reduced.Compared with the I/ R+ Dex group, the areas of myocardial infarction in the I/ R+Dex+5-HD and I/ R+5-HD groups,were significantly reduced, and the expressions of Cx43 and p-Cx43 were reduced. The differences were statistically significant ( P< 0.05 ). Conclusions Dexmedetomidine preconditioning can promote the expression and phosphorylation of Cx43, and the opening of the mito-KATP channel, and reduce ischemia-reperfusion injury of isolated hearts.

Abstract: Objective To investigate the molecular mechanism of miR-338-3p in the proliferation, migration, invasion, and apoptosis of esophageal cancer cells and its targeted regulation of WNK1. Methods Human normal esophageal epithelial cell line Het-1A and human esophageal cancer cell lines Eca-109, EC-1, and EC9706 were cultured in vitro. The expression levels of miR-338-3p and WNK1 were measured by qRT-PCR and Western blot, respectively. In EC9706 cells, miR-con, miR-338-3p mimics, si-con, si-WNK1, miR-338-3p mimics and pcDNA, and miR-338-3p mimics and pcDNA-WNK1 were transfected into EC9706 cells. MTT assays were used to detect cell proliferation, flow cytometry was used to detect apoptosis, and Transwell assays were used to detect migration and invasion abilities. A dual luciferase reporter assay was used to assess the relationship between miR-338-3p and WNK1. Results Compared with Het- 1A, the expression levels of miR-338-3p in esophageal cancer cell lines Eca-109, EC-1, and EC9706 were reduced significantly (P<0.05) and the expression levels of WNK1 mRNA and protein were increased significantly (P< 0.05). Transfection of miR-338-3p mimics or si-WNK1 significantly reduced the viability, migration, and invasion of EC9706 cells (P<0.05), and increased the apoptosis rate of EC9706 cells (P<0.05). The dual luciferase reporter assay confirmed that miR-338-3 targeted WNK1. Cotransfection of miR-338-3p mimics and pcDNA-WNK1 obviously reversed the effects of miR- 338-3p mimics on cell proliferation, migration, invasion, and apoptosis. Conclusions MiR-338-3p downregulates WNK1 in esophageal cancer, thereby inhibiting the proliferation, migration, and invasion of esophageal cancer cells and inducing apoptosis.

Abstract: Objective To investigate the effect of astragalus polysaccharides (APS) on autophagy of granulosa cells in polycystic ovary syndrome ( PCOS) rats by regulating the silent mating type information regulation 2 homolog 1 (Sirt1) / forkhead box transcription factor O1 (FoxO1) pathway. Methods Ovarian granulosa cells were isolated from rats and identified by follicle stimulating hormone receptor (FSHR) immunofluorescence. CCK8 was used to assess the effect of APS on the proliferation of ovarian granulosa cells. Ovarian granulosa cells were treated with 1× 10^-5 mol / L testosterone propionate and 10 μmol / L C2 ceramide for 24 h to induce the autophagy model of PCOS rat granulosa cells. CCK8 was used to measure cell proliferation. Autophagy was observed by transmission electron microscope. Protein expression of Sirt1, FoxO1, and microtubule-associated protein 1 light chain 3 ( LC3 ) was detected by Western blot. Results Immunofluorescence showed that average positive expression of FSHR protein in rat ovarian granulosa cells was 93. 18% > 90%. In 0, 100, 200, and 400 μg / mL APS-treated normal ovarian granulosa cells, there was no significant difference in OD₄₅₀ after adherence at 0 or 24 h (P > 0. 05). Compared with the normal group, a large number of autophagy bodies appeared near the nucleus of the model group, and double and single layer membranes wrapped the cytoplasm to form a closed and round structure. Some of the autophagy body inner membrane had dissolved and there was a single membrane structure around the autophagosome, which contained some degraded cytoplasm similar to the autophagosome structure. The cell structure of the 100 μg / mL APS group was similar to that of the model group. With the increase of APS dosage, the number of autophagy bodies decreased and the cells were normal in the 400 μg / mL APS group. There was no significant difference in OD₄₅₀ between normal, model, and 100, 200, and 400 μg / mL APS groups at 0 h of cell adhesion (P> 0. 05). After 24 h of cell adhesion, compared with the normal group, OD₄₅₀ was lower in the model group (P< 0. 05) and the protein levels of Sirt1, FoxO1, and LC3II/ LC3I were higher (P< 0. 05). Compared with the model group, OD₄₅₀ was higher in 100, 200, and 400 μg / mL APS groups (P< 0. 05) and the protein levels of Sirt1, FoxO1, and LC3II/ LC3I were lower (P< 0. 05). Conclusions APS inhibits autophagy of granulosa cells in PCOS rats, which may be mediated by inhibiting the autophagy pathway Sirt1 / FoxO1.

Abstract:The development of alternative tests for skin corrosion and skin irritation were reviewed, and the Integrated Approach on Testing and Assessment (IATA), which was recently adopted by the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), was introduced. Focusing on the principles, Methods and scope of various alternative tests, the advantages and limitations of these tests in the application of IATA will be discussed to provide guidance for the classification of chemicals causing skin corrosion and irritation by effective utilization of the alternative tests and the data derived from these tests.

Abstract:The HIV virus is widespread worldwide, leading to the serious and infectious acquired immunodeficiency syndrome (AIDS), and serious impacts on human life, health and social development. Although highly active antiretroviral therapy can inhibit HIV virus replication, it is not able to eliminate virus from the body. Preventive vaccines are an important tool against HIV, but because the virus has genetic diversity and strong variability, such vaccines must be able to induce broadly neutralizing antibodies ( bNAbs) that broadly and effectively neutralize HIV strains. Research targeting the induction and generation of bNAbs for the prevention of HIV has many challenges, and it is necessary to further strengthen the scientific and technological efforts in related research directions. This review summarizes the latest progress in HIV bNAbs, including biological characteristics, production mechanisms, induction strategies and other aspects, with the goal to provide basic information and possible directions for subsequent research.

Abstract:Stress-induced gastric ulcers( SGU) is a disease in which the body suffers from stress,Resultsing in cell metabolism disorders and damage, and eventually causing acute erosion and ulcers of the gastric mucosa. The pathogenesis of SGU is still unclear. Understanding the signaling pathways related to SGU is of great significance for further research into the pathogenesis of SGU and the search for potential therapeutic targets. This article reviews the research progress of SGU-related signal pathways, and shows that SGU and the JAK/ STAT, Nrf2 / HO-1, NF-κB, ERK1 / 2, Hedgehog, TLR, and PI3K/ Akt signaling pathways are closely related. The goal of this review is to provide a certain scientific basis for the study of the pathogenesis of SGU and potential new treatment method .

Abstract:Antibodies are Y-shaped proteins secreted to identify and neutralize pathogenic microorganisms, such as bacteria and viruses, which maintain our health. Oral antibodies that enter the intestinal tract provide intestinal passive immunity to protect the intestinal tract from infection by pathogenic microorganisms. In recent years, a growing number of studies have shown that the gastric environment does not affect some specific antibodies, which provide immediate protection in an animal’s gut. The development process, action mechanism, preparation route, and stability characteristics of oral antibodies are introduced and the protective effect of natural antibodies and genetically engineered antibodies on intestinal infections in animals by oral intake are summarized in accordance with the practical application.

Abstract:According to data on China’s disease burden in 2019 published by the Lancet, alcohol consumption is the 10th leading risk factor for death. However, the pathogenesis of alcoholic liver injury caused by drinking is very complicated, and there is still no final conclusion. The toll-like receptor 4 signaling pathway has a key role in the occurrence and development of alcoholic liver injury. Therefore, this article reviews the role of the toll-like receptor 4 signal transduction pathway in alcoholic liver injury.

Abstract:Oxidative stress is an major factor that affects aging and neurological diseases, which plays an crucial role in the development and progression of multiple neurodegenerative diseases. Amyloid-beta protein ( Aβ) is a major component of senile plaques, and its aggregation and abnormal deposition are major contributors to the pathogenesis of Alzheimer’s disease (AD). Studies have shown that oxidative stress triggered by Aβ deposition induces neuronal loss, cell death in cognitive memory-related brain regions, and finally causes the occurrence and development of AD pathology. This article focuses on the mechanism of toxic production of amyloid peptide in the occurrence and development of AD, the oxidation process of macromolecules and the process of the interaction between amyloid peptide and oxidative stress to clarify the relationship between amyloid peptide and oxidative stress in the occurrence and development of AD. This review provides strong theoretical support and research directions to promote studies on antioxidants in AD.

Abstract:In this paper, the theoretical basis, animal selection, modeling stress source, modeling time, and evaluation of indexes of sub-health animal models were summarized. Research on the theoretical basis and evaluation indexes of sub-health animal models is important and comprehensive analysis of multiple indexes should be conducted to identify ideal, mature, and recognized sub-health animal models.