Abstract:Objective To investigate the effects of tetrandrine on early development in zebrafish embryos and the expression of multidrug resistance gene abcb4 and its mechanisms. Methods We used a drug toxicity test to analyze the mortality, hatching rate, heart rate, and deformity rate of zebrafish embryos treated with tetrandrine. Wild-type zebrafish embryos were divided into a blank control group, doxorubicin treatment group, vinblastine treatment group, tetrandrine treatment group, tetrandrine combined with doxorubicin treatment group, and tetrandrine combined with vinblastine treatment group. Drugs were administered to each group of embryos until the fifth day, and the embryos were then used for the experiment. Expression of the abcb4 gene was detected using real-time fluorescent quantitative PCR, and drug resistance was detected using the Rhodamine 123 test. Results Compared with the control group, low-dose tetrandrine had no teratogenic lethal effects on zebrafish embryos. High-dose tetrandrine significantly inhibited embryonic hatching rate and had clear lethal and teratogenic effects. Compared with the control group, the mRNA of the abcb4 gene increased when treated with doxorubicin and vinblastine alone, but decreased when exposed to tetrandrine combined with doxorubicin and vinblastine. The Rhodamine 123 experimental result showed evidence of drug resistance in zebrafish treated with doxorubicin and vinblastine alone, and indicated that tetrandrine combined with doxorubicin and vinblastine could reverse drug resistance. Conclusions Tetrandrine has low toxicity for zebrafish embryos early in development, and can reverse drug resistance to doxorubicin and vinblastine. These data suggest that tetrandrine may improve sensitivity to chemotherapy drugs and thus may enhance the therapeutic effect.

Abstract:Objective To explore changes in motor coordination, cognitive function, and anxiety-like behavior as well as pathological characteristics in α-synuclein A53T transgenic mice. Methods We used α-synuclein A53T transgenic mice with a C57BL/ 6 background as the experimental group, and included a negative control group. The open field and cylinder tests were used to examine mouse anxiety levels, the rotarod and grip tests were used to evaluate movement disorders, and the Morris water maze and a fear conditioning test were used to evaluate cognitive ability. Pathological features were studied using immunohistochemical staining and mitochondrial morphology was observed via electron microscopy. Results Compared with the control group, α-synuclein A53T transgenic mice moved a greater distance, indicating that the mice were overactive. Further, freezing time was decreased, indicating cognitive impairment. We found no differences in performance in the cylinder test, rotarod test, grip test, or Morris water maze. In the α-synuclein A53T transgenic mice, levels of phosphorylated α-synuclein in the substantia nigra, striatum, piriform cortex, and hippocampus were increased, and we found Lewy bodies in the prefrontal cortex. Further, increased deposition of α-synuclein in the substantia nigra and striatum was observed, and the number of TH cells in the substantia nigra decreased significantly. Compared with the control group, mitochondria fission in the amygdala was increased, and the mitochondrial contents were unclear. Conclusions Cognitive function was impaired in α-synuclein A53T transgenic mice. Pathological characteristics included α-synuclein / LBs deposits in the prefrontal and piriform cortex, decreases in dopaminergic neurons in the substantia nigra, and altered mitochondrial morphology in the amygdala. α-synuclein A53T transgenic mice may be an appropriate model of synucleinopathy-related cognitive disease such as Lewy body dementia and dementia related to Parkinson’s disease.

Abstract:Tree shrew is a new type of experimental animal model with broad application potential. However, the current distribution of intestinal bacteria and pathogens in the wild Tupaia belangeri yaoshanensis (T.b. yaoshanensis) in Guangxi are still unclear. Therefore, we performed for the first time the isolation and identification of the bacteria cultured in the subspecies of the wild T.b. yaoshanensis in Guangxi. Thirty-five strains of bacteria were isolated from 19 T. b. yaoshanensis subspecies and identified by 16S rRNA sequence analysis. There are 20 species of bacteria in 13 genera and 7 families, and the main flora in the intestinal tract of the wild T. b. yaoshanensis in Guangxi include Escherichia coli, Citrobacter freundii, and Proteus mirabilis. Moreover, to study the drug susceptibility of intestinal bacteria isolated from the feces of T.b. yaoshanensis collected from Dayaoshan in Guangxi, a drug sensitivity test was conducted using some of the isolated intestinal bacteria. The intestinal bacteria of T.b. yaoshanensis were sensitive to ceftazidime, gentamicin, and levofloxacin, and resistant to cefazolin and sulfamethoxazole. This is the first to grasp the diversity and potential pathogenicity of the fecal flora of the wild T. b. yaoshanensis in Guangxi. These result provide the scientific basis for the isolation and quarantine of T.b. yaoshanensis, laboratory feeding, and the prevention and treatment of common digestive tract diseases.

Abstract:Objective We examined the expression level of plasma cytokines in SIVmac239-infected rhesus monkeys before and during antiviral treatment and assessed correlations with disease characteristics. Methods The SIVmac239 virus was administered intravenously to healthy Chinese rhesus monkeys, which were then treated with HAART (Highly active antiretroviral therapy) as an AIDS treatment model. Flow cytometry was used to detect CD4⁺T cell counts in peripheral blood, and Luminex was used to detect plasma cytokines. Results After HAART treatment, the plasma viral load of SIVmac239-infected rhesus monkeys decreased below the detection limit, and the CD4⁺ T cell count and CD4⁺ / CD8⁺ ratio recovered to pre-infection levels. Expression of all cytokines detected after infection, except IL-8, was elevated. After HAART treatment, except for a decrease in IP-10 expression levels, IL-8 remained unchanged and other cytokine levels continued to rise. After stopping drug treatment, levels of pro-inflammatory factors TNF-α, antiviral factors IFN-γ and IFN-α, and the expression of chemokine MCP-1 decreased. The pro-inflammatory factor IL-6 and the anti-inflammatory factor TGF-siowere most strongly correlated with plasma viral load. Conclusions Most cytokines were elevated after infection and HAART treatment, and expression of most cytokines decreased after stopping the drug, although they remained higher than normal. Levels of IL-6, TGF-β1, and IP-10 cytokines are consistent with clinical manifestations regardless of changing trends or correlations with disease characteristics.

Abstract:Objective To establish a sensitive droplet digital PCR ( ddPCR) assay for measuring the proviral DNA load in PBMCs (peripheral blood mononuclear cell) and tissues from SIV-infected animals. Methods According to the standard qPCR method , we first optimized the annealing temperature of the droplet dPCR, and then determined the detection range of the ddPCR. This was followed by correlation analysis of ddPCR and qPCR via detection of the 10-fold serially diluted pGEM-SIVgag477. We repeatedly tested 7 DNA samples extracted from PBMCs of SIV-infected monkeys to study the repeatability of the method . Results The annealing temperature of the ddPCR was determined to be 60°C and the detection range was 0. 3~ 3. 96 × 10⁴ copies/ μL. The correlation coefficient of ddPCR and qPCR was in the range of 0. 9981. Conclusions We established an absolute quantitative method for SIV DNA analysis based on droplet dPCR. This method can be used to accurately quantify the proviral DNA load and represents an effective technique for the measurement of viral reservoirs in SIV research.

Abstract:Objective To analyze the transcription profile of Mycobacterium tuberculosis ( Mtb )-infected macrophages in which the pdl1 gene has been knocked out and screen PD-L1 related candidate genes in Mtb -infected macrophages (MΦ). Methods pdl1^{Flox / -} mice were constructed, and homozygous (pdl1^{Flox / Flox}with Cre) and heterozygous (pdl1^{Flox / -} with Cre) mice with targeted inactivation of the pdl1 gene in MΦs were bred by the Cre / loxP technique and verified by PCR and FACS. Peritoneal MΦs were isolated from different substrains of mice, and those isolated from littermate negative mice (pdl1^{Flox / Flox}) were used as controls. Twenty-four hours after infection, the transcript profiles in the infected and uninfected groups were sequenced by RNA-Seq, and bioinformatics analysis was performed. Results pdl1- specific knockout mice were successfully generated and identified by PCR and FACS. The pdl1^{Flox / Flox}with Cre, pdl1^{Flox / -} with Cre, and pdl1^{Flox / Flox} infected groups were compared with their corresponding non-infected groups. Gene Ontology (GO) functional enrichment analysis showed that the most significant enrichments were immune response (P< 0. 01) and immune system processes (P< 0. 01). The seventeen candidate genes identified were regarded as specific genes related to PD-L1 in Mtb infection. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the most significantly enriched pathways included Toll-like receptor (P< 0. 01) and nuclear factor kappa-B (NF-κB) (P< 0. 01) signaling pathways, and six candidate genes related to PD-L1 were screened. Conclusions Through transcription analysis, seventeen genes related to the immune response, including Ccl2, Qa5, and Il12a, and six genes in immune - and inflammation-related metabolic pathways, including Ptgs2, Cd40, and Card11, were identified as specific candidate genes related to PD-L1 in macrophages infected with Mtb. Except for Il6, all candidate genes were selected for this research.

Abstract:Objective A mouse model of alcoholic cardiomyopathy was established with liquid feed, which provided a good animal model to study alcoholic cardiomyopathy. Methods Sixteen-week-old C57BL/ 6 mice ( n = 21 alcohol group, n = 9 alcohol-free group) were fed with liquid feed with or without alcohol. The alcohol concentration in the feed was gradually increased from 4. 8% to 5. 4% for 8 weeks, and weight and mortality were monitored. Echocardiography and pathology were performed after 8 weeks. Results The weights of the alcohol feeding group began to decrease by the second week. Compared with the control group, body weight was significantly reduced. In addition, seven mice (33. 3%) died during the alcohol feeding period, whereas none of the mice in the control group died. The result of cardiac ultrasounds showed that the mice in the alcohol group had significantly thinner anterior and posterior ventricles, larger ventricular diameters, and the ejection fraction and shortening rate of the short-axis of the mice were significantly decreased. The heart / body mass indexes of mice in the alcohol group were significantly larger than those of the control group, and HE staining confirmed that the hearts of the mice in the alcohol group were significantly enlarged. Conclusions After 8 weeks of feeding with alcoholic liquid feed, the hearts of mice showed significantly larger and thinner left ventricular walls and cardiac dysfunction. Therefore, this method can be used to successfully establish a mouse model of alcoholic cardiomyopathy.

Abstract:Objective Objective Based on the network pharmacology approach, this paper aimed to study the useful material base and functioning mechanism of Gardenia jasminoides Ellis-processed Ligusticum for the treatment of depression. Their antidepressant effects were initially tested and verified using ICR( Institute of Cancer Research) mice. Methods Effective compounds of Gardenia jasminoides Ellis-processed Ligusticum wallichii were collected from the Web of Science, CNKI, and ScienceDirect Databases. Then, the chosen ingredients were further selected or screened according to their generic drug-like principle. The Swiss Target Prediction Database and GeneCards were used to predict and identify the target components with antidepressant activity. Furthermore, the String Database was used to annotate protein interactions, and ClueGO software was used to perform the enrichment analysis of concentrated signal passages for those key functioning targets of the antidepressant activity. Based on the above information, the “ ingredient-target-signal-pathway” network was constructed, and its topological analysis was conducted by Cytoscape 3. 7. 0 software. Based on the result of this analysis, the top 4 compounds were tested for their antidepressant effect in ICR mice. Results Based on Cytoscape 3. 7. 0 software, the active ingredients with antidepressant effects were 4-methoxyl-phenethyl-butyl ether, jasminoside J, Gardenal-I, and butylphthalide. The main effective targets were COMT, HTR1A, DRD 2, SLC6A4, SLC6A3, MAOA, GRM5, DRD4, DRD3, HTR2A, HTR3A, GRIA1, APP, HTR1B, and GRM1. The main pathways of antidepressants were serotonergic and dopaminergic synapses. Animal experiments showed that the positive control groups, the medium and high dose groups of butylphthalide and Gardenal-I, and the high dose groups of 4-methoxyl-phenethyl-butyl ether could significantly reduce the immobility time compared with the blank groups, which further verified the antidepressant activity of these ingredients. Jasminoside J could not reduce the immobility time, indicating that it did not show an antidepressant effect. Conclusions Based on network pharmacology and animal experiments, the active ingredients with antidepressant activity were 4- methoxyl-phenethyl-butyl etherGardenal-I, and butylphthalide, which provide references for further research.

Abstract:Objective We examined the inclusion ratio of SMN2 exon 7 in different tissues from SMA mice and screened related splicing factors. Methods Ratios of SMN2 exon 7 inclusion in neural and non-neural tissues were analyzed by RT-PCR and non-denaturing PAGE electrophoresis. The expression levels of splicing factors in the brain, spinal cord, and non-neural tissues were analyzed by QPCR. Results The inclusion ratio of SMN2 exon 7 in brain and spinal cord tissues was significantly higher than that in non-neural tissues. The QPCR screening result showed that the expression of Nova1 / 2 was significantly higher in the brain and spinal cord than in most non-neural tissues. The difference analysis showed that the mRNA levels of Srsf7 / 9 and Nova2 in the spinal cord of SMA type I mice were significantly higher than those in control mice. Conclusions The high expression of Srsf7 / 9 and Nova1 / 2 is positively correlated with significant increases in the inclusion ratio of SMN2 exon 7 in neural tissues, indicating that Srsf7 / 9 and Nova1 / 2 may be involved in the splicing regulation of SMN2.

Abstract:Objective We systematically studied the effects of initial mating age on reproductive performance in NIH mice. Methods Thirty pairs of mice were divided into 4 groups according to initial mating age: 50, 60, 70, or 85 days old. For the first to sixth litters from each pair, we recorded the average litter size, number of weaned mice, weight of the natal mice and weaned mice, and calculated the weaning rate and day, and compared these between the age groups. Results Compared with the 50-day-old group, the 70- and 85-day-old groups were significantly or extremely significantly different in terms of the average litter size, number of weaned mice, weaning rate, and weight of the natal mice and weaned mice (P< 0. 05, P < 0. 01). Compared with the 60-day-old group, the 70 - and 85-day-old groups were significantly different in terms of average body weight and the number of weaned mice (P< 0. 05). There were no differences in the intervals between litters among the groups (P> 0. 05). The average litter size in NIH mice for the second and third litters was significantly higher than that for the first litter (P< 0. 05). The fifth and sixth litters had a significantly decreased average size (P< 0. 05). The number of weaned mice in the third and fourth litters was different from that in the first litter (P< 0. 05). The average body weight and lactation rate of the mother increased with the age of parity (P< 0. 05, P< 0. 01). The average body weight and weaning rate of the infant mice increased with the age of parity. There were no significant differences in the average body weight of the weaned mice (P> 0. 05). Conclusions NIH mice have better reproductive performance at 70 ~ 85 days of age, and the second and third births are stable in terms of reproductive performance. For propagation of research animals, up to six litters are recommended.

Abstract:Objective To establish a modified rat model of severe traumatic hemorrhagic shock ( STHS) and explore the protective effect of anesthesia on the development of STHS in a rat model. Methods Forty adult healthy male SD rats were randomly divided into four groups. The normal group was anesthetized with catheterization of the bilateral femoral artery and left femoral vein, and the rats waiting for consciousness or maintenance of anesthesia were divided into the conscious control group (CC, n = 10) and the anesthetic control group (AC, n = 10). The rats that suffer from severe traumatic hemorrhagic shock experience an open wound of the abdominal white line 5 cm with 50% bloodletting, and than, they were separated into two groups: the conscious traumatic hemorrhagic shock group (CTHS) and the anesthetic trauma hemorrhagic shock group (ATHS, n = 10). The general physiological conditions of rats in each group were observed, and the following hemodynamic indexes of experimental rats were continuously monitored: mean arterial pressure (MAP), heart rate (HR), and maximum rise / fall rate of left ventricular pressure (±dp / dtmax). Arterial blood gas indexes, including pH value, the partial pressure of oxygen (PaO² ), the partial pressure of carbon dioxide (PaCO² ), hemoglobin concentration (ctHb), lactic acid (Lac), blood glucose (Glu), bicarbonate concentration ( cHCO³ - ), and base excess (BE), were also measured. At the end of the experiment, HE staining was performed to observe heart, liver, lung, and kidney injury in the rats. Results There were significant differences in the changes in HR and ±dp / dtmax with time in CTHS and ATHS groups (P < 0. 01), whereas HR and ±dp / dtmax decreased at first (T1) and then increased or stabilized (T2, T3, T4, T5, T6) in the CTHS group. After shock, the MAP in the ATHS group showed a gradual upward trend and finally returned to the normal level of 25%-40%, while that in the CTHS group decreased rapidly after the compensatory growth period. In CTHS and ATHS groups, PH, PaCO² , ctHb, cHCO³ - , and BE gradually decreased, and except for PH and ctHb, the decreases in the CTHS group were significantly higher than those in the ATHS group (P < 0. 01). Glu, Lac, and PaO2 showed a gradual upward trend, and the amplitude of the increase in the CTHS group was significantly higher than that in the ATHS group (P < 0. 01). The degree of liver, heart, lung, and kidney injury in the ATHS group was significantly lower than that in the CTHS group. Conclusions Anesthesia exhibits a protective effect on the development of severe traumatic hemorrhagic shock in rats, which can improve hemodynamics, reduce the accumulation of respiration and metabolites, and limit the degree of organ injury.

Abstract:Objective To study the effects of four organic solvents, including methanol, isopropanol, acetone, and dimethyl sulfoxide (DMSO), on the development of zebrafish embryos, especially eye development, and provide clues for their use in zebrafish studies. Methods Zebrafish embryos ( 12 hours post-fertilization) were exposed to 0. 5% ethanol, 1% isopropanol, 1. 5% acetone, and 2. 5% DMSO for 60 hours. The survival rate, eye size, gross morphological changes, and retinal histological features were observed. Results The survival rates of the control group and the groups exposed to ethanol, isopropanol, acetone, and DMSO were 96%, 93%, 90%, 90%, and 86%, respectively. The morphology of the zebrafish was normal in the control group, whereas there were morphological changes, such as pericardial edema, hemorrhage, yolk defect, and body bending, in the solvent-treated groups. Specifically, DMSO induced the most severe changes, and ethanol the least. Variance analysis showed that there was no significant difference in the ratio of eye length to body length between the organic solvent-treated groups and the control group, but the ratio of the eye area to body area in the group treated with DMSO was significantly lower than that in other groups. In addition, compared with the control group, the retina stratification in the group treated with four organic solvents was normal. The signals of cone cells, rod cells, and retinal neurons in the ethanol, isopropanol, and acetone exposed groups were normal, but the signals of each cell were weak in the group treated with DMSO. Conclusions Therefore, we should carefully select the solvent carrier for zebrafish studies and perform preliminary experiments to determine the safest concentration.

Abstract:Objective To analyze the antitumor effects of microRNA-144 (miRNA-144) gene overexpression and corresponding changes in intestinal flora in a mouse model of hepatoma. Methods First, we transplanted ascites hepatoma cells in mice. To observe the general effects of overexpression of the miRNA-144 gene, we evaluated the histopathological morphology of the liver and intestine, abundance and diversity of the intestinal flora, and function of the intestinal barrier in a mice model of liver cancer. Occludin, ZO-1, miRNA-144, and ZO-1 proteins were detected using real-time fluorescence quantitative PCR and a western blot. Conclusions Overexpression of miRNA-144 can inhibit the development of primary liver cancer, as well as improve the intestinal microecological environment and intestinal mucosal function in mice. The mechanism may be related to the up-regulation of mRNA and protein expression of Occludin and ZO-1.

Abstract:Objective To investigate whether exosomes (Exos) secreted by mesenchymal stem cells (MSCs) regulate cardiac autophagy and cardiac function in rats with myocardial ischemia through miR-21-5p. Methods In vitro,the effect of MSC exos on H₂O₂ stimulated H9C2 cells was observed. Cell viability was detected by the CCK- 8 assay, apoptosis was detected by flow cytometry, reactive oxygen species ( ROS ) production was analyzed by fluorescence microscopy, and autophagy-related proteins and autophagy formation were detected by immunoblotting and fluorescent GFP- LC3. In rat model of myocardial ischemia-reperfusion injury ( MI/ IR), the effects of MSC exos on cell apoptosis, myocardial LC3b expression, and cardiac function were examined by TUNEL assay, immunohistochemistry, and echocardiography. Results In vitro, MSC-Exos significantly increased the activity of H9C2s stimulated by H₂O₂(P<0. 05) and decreased the production of ROS and the rate of apoptosis (P<0. 05). Compared with the H₂O₂+MSCs-Exos group, the cell viability in the H₂O₂+MSC-ExossimiR^-21-5p group was significantly decreased (P<0. 01), whereas ROS production and apoptosis were significantly increased (P<0. 01). Western blot analysis showed that compared with the H₂O₂ group, the expression of LC3B-Ⅱ/ LC3B-I and LC3B-II in the H₂O₂+MSC-ExossimiR^-21-5p group was significantly lower than that in the H₂O₂+MSCs-Exos group (P<0. 05), while the expression of p62 was significantly increased (P<0. 05). Autophagy flux result : Compared with the H₂O₂ group, GFP-LC3 was increased in the H₂O₂+ MSCs-Exos group. Furthermore, Compared with the H₂O₂+ MSCs-Exos group, the number of GFP-LC3 points in the cells of the H₂O₂+ MSC-ExossimiR^-21-5p group was significantly reduced (P<0. 05). in vivo, RT-qPCR analysis showed that there was a positive correlation between the expression of miR-21-5p in MSCs-Exos and MI/ RI. Compared with other groups, the expression of LC3B in the MI/ RI+ MSCs-Exos group was significantly increased (P<0. 01), myocardial apoptosis was significantly reduced (P<0. 01), and the fraction shortening rate (%FS) and left ventricular ejection fraction (LVEF) were significantly increased (P<0. 05). Conclusions MSCs-Exos can improve cardiac function in MI/ RI rats by regulating myocardial autophagy, and its mechanism may be related to miR-21-5p transfer.

Abstract:Objective We constructed a curcumin ( CUR) nanoemulsion drug delivery system to study its protective effect on myocardial ischemia-reperfusion in rats and elucidate the underlying mechanisms. Methods Curcumin nanoemulsions (CUR-NMs) were produced and morphologically characterized by transmission electron microscopy. The rat model of myocardial ischemia-reperfusion was established by ligation of the left anterior descending coronary artery. The rats were randomly divided into sham operation, model, CUR treatment, and CUR-NMs treatment groups. The CUR treatment and CUR-NMs treatment groups were intraperitoneally administered CUR ( 20 mg / kg) and CUR-NMs ( 20 mg / kg) 4 h before ischemia. The hemodynamic changes were detected in each group of rats. TUNEL staining was used to measure the apoptosis of rat myocardial cells. CK, LDH, MDA, and SOD levels were detected using commercial kits. The protein expression of calpain1, calpastatin, Bcl-2, and cleaved-caspase 3 were detected by western blot. Results The prepared CUR-NMs are uniform in size, round in shape, and have a particle size of (121 ± 23) nm. After 30 minutes of ischemia and 2 hours of reperfusion, Left ventricular developmental pressure (LVDP), maximal left ventricular pressure rising rate ( dp / dtmax ), and maximal left ventricular pressure decreasing rate (-dp / dtmax ) indicators in the model group were significantly decreased (P<0. 01), serum LDH, CK, and MDA were significantly increased, and SOD was significantly reduced (P< 0. 01). Compared with the model group, the LVDP, dp / dtmax, and -dp / dtmax of the CUR-treated and CUR- NMs-treated groups were all increased to varying degrees (P< 0. 05 or P< 0. 01), whereas LDH, CK, and MDA were significantly decreased, and SOD was significantly increased ( P < 0. 05 or P< 0. 01). Compared with the CUR-treated group, LVDP, dp / dtmax, and -dp / dtmax increased in the CUR-NMs treatment group (P< 0. 01), serum LDH, CK, and MDA decreased, and SOD increased ( P < 0. 05 or P < 0. 01). Compared with the sham operation group, myocardial apoptosis in the model group was significantly increased (P<0. 01), the expression levels of calpain1 and cleaved-caspase 3 were significantly increased, and the levels of Bcl-2 and calpastatin were significantly reduced (P<0. 01). Compared with the model group, myocardial apoptosis was significantly reduced in the CUR-treated and CUR-NMs-treated groups ( P< 0. 01), the expression levels of calpain1 and cleaved-caspase 3 were significantly reduced, and the levels of Bcl-2 and calpastatin were significantly increased (P<0. 05 or P<0. 01). Compared with the CUR-treated group, myocardial apoptosis was significantly reduced in the CUR-NMs-treated group ( P < 0. 01), calpain1 and cleaved-caspase 3 proteins were downregulated, and Bcl-2 and calpastatin proteins were upregulated (P<0. 05 or P<0. 01). Conclusions CUR-NMs can improve myocardial ischemia-reperfusion injury in rats more effectively than CUR. This effect may be related to enhanced cell uptake or inhibited calpain1 protein expression and activity.

Abstract:Efforts to improve the welfare ethics review of laboratory animals have been increasingly valued in the development of human ethics and morality and the accuracy of experimental data. Currently, laboratory animals, as basic and important scientific research resources, play a major role in the development of life sciences, medical research, and pharmaceutical research. To protect the welfare of laboratory animals, regulate the ethical review of laboratory animals, and monitor the professional behavior of laboratory animal practitioners, the regulation of welfare and ethics of laboratory animals and the Institutional Animal Care and Use Committee ( IACUC) have been established in Chinese scientific research institutions. These can effectively ensure laboratory animal welfare and animal experimental ethics. Sadly, not all institutions have these committees and not all guidelines and regulations are enforced. There appear to be some problems, such as awareness, processes, and operations. These will be described in this paper, which will help to analyze the reasons for these issues, propose countermeasures, and provide suggestions to overcome these limitations.

Abstract:Epilepsy is a relatively common chronic neurological condition that is often characterized by unprovoked recurrent seizures that can be very disruptive for the lives of patients and their families. Na⁺ / K⁺ -ATPase (NKA) is a transmembrane protein distributed widely in most cells of mammalian animals. NKA is critical for the maintenance of the ionic gradient between intracellular and extracellular space, the uptake and release of neurotransmitters, and energy metabolism. Complicated patterns of change in NKA activity have been observed in the brains of epileptic patients and animals. Excessive changes in NKA activity may upregulate susceptibility to epilepsy in non-human animals, although NKA activity decreases significantly after recurrent seizures. In this article, we reviewed the classification, distribution, and function of NKA, as well as interactions and possible mechanisms between NKA activity and seizures.

Abstract:Objective To describe evaluations of the common behavioral paradigm of maternal separation in rats and mice and recent findings regarding the underlying biological mechanisms, and to analyze experimental data regarding the specific effects of maternal separation duration and separation frequency. Methods Recent studies examining the cognitive and psychological effects of early life stress on rats and mice were obtained using multiple search platforms. Behavioral evaluation method. Results and potential mechanisms are described. Results The establishment of an animal maternal separation model represents an important method for exploring long-term psychosomatic diseases related to negative events in early life, with wide applicability. Conclusions At present, different researches have explored the cognitive, psychological changes and pathogenesis of animal models in many aspects and made some progress. However, the cognitive and behavioral changes caused by different separation frequencies and durations are uncertain, and their effects on gene expression in offspring and parents warrant further exploration.

Abstract:Type 2 diabetes mellitus (T2DM) is a metabolic disease that seriously threatens the health of patients. Modern medicine is mainly used to control blood sugar stability and prevent T2DM complications. T2DM patients are required to take hypoglycemic agents for life. Although chemical drugs have a definite curative effect, they also cause several side effects after long-term use, which seriously limits their use. Traditional Chinese medicine (TCM) has a long history of blood glucose-lowering abilities, and it has unique advantages in the treatment of complex diseases ( i. e., T2DM), but its mechanism is not fully understood. Recent studies have shown that TCM can lower blood glucose by regulating gut microbiota to improve glucose metabolism, which provides new method and ideas for the prevention and treatment of T2DM. This article reviews the recent progress in the understanding of the roles and mechanisms of TCM, its extracts, and compound preparations to lower blood glucose by regulating gut microbiota. We also provide references and recommendations for future research on the blood glucose-lowering ability of TCM.

Abstract:ANXA1 (Annexin-A1), originally known as an anti-inflammatory mediator, has been implicated in cancer. However, its functions in cancer growth and metastasis are unclear and conflicting. ANXA1 expression may be dependent on the stage or type of cancer. ANXA1 acts as a double-edged sword as it is generally antiproliferative, protecting cells against DNA damage, despite promoting metastasis. The use of ANXA1 as a therapeutic or prognostic marker for cancer must be carefully timed, and it must be employed carefully depending on the cancer type, grade, and stage.

Abstract:Microglia, which are innate immune cells in the brain, play an irreplaceable role in the pathogenesis of Alzheimer’s disease. The M1 / M2 model has previously been used to explain the function of microglia. However, advances in technology, especially in cell transcriptome genomics, i. e., proteomics, have enabled a more comprehensive understanding of microglia. Disease-related microglia, one of the subtypes established from the perspective of the cell transcriptome, is of great significance for the construction of new subtypes of microglia. Indeed, this subtype may facilitate the prediction of many new AD risk sites in future research.