Abstract: Objective To explore an establishment method and influencing factors of an intimal hyperplasia model of common carotid artery in rabbits. Methods Thirty New Zealand white rabbits, half male and half female, were randomly divided into a sham operation group, high fat + unilateral cannula group (divided into 2- and 3-week subgroups in accordance with the modeling time), and hyperlipidemia + bilateral cannula group ( divided into 2 - and 3-week subgroups in accordance with the modeling time). In the unilateral cannula group, a silicone tube (20 mm in length and inner diameter of 1 mm) was placed on the lateral side of the left common carotid artery and fixed, whereas in the bilateral cannula group, a silicone tube was placed on the lateral side of the bilateral common carotid artery and fixed. Both groups were fed a 2% cholesterol diet for 2-3 weeks starting from the day after the operation. In the sham operation group, the common carotid artery was separated, no vascular cannula was performed, and the rabbits were fed a regular diet. At 2 and 3 weeks after the operation, pathomorphological changes of the injured common carotid artery were observed, the index of intimal hyperplasia was measured by morphometry, and expression of α-smooth muscle actin ( α-SMA), osteopontin (OPN), type I collagen (Col-Ⅰ), inflammatory response factor interleukiN-1β ( IL-1β), and tumor necrosis factor-α (TNF-α) in intimal hyperplasia was determined by immunohistochemistry. Results After treatment with high fat and the silicone tube for 2 or 3 weeks, intimal hyperplasia was found in the common carotid artery. The intimal area, intimal thickness, intimal area proliferation rate, and intimal thickness were increased significantly. Intimal hyperplasia in the bilateral cannula was more obvious than that in the unilateral side, and intimal hyperplasia at 3 weeks was more serious than that at 2 weeks. After 3 weeks of the bilateral cannula, expression of α-SMA in the vascular intima was reduced significantly and expression of OPN, Col-Ⅰ, IL-1β, and TNF-α was increased significantly. Conclusions A model of intimal hyperplasia can be successfully established using high fat and a common carotid artery silicone cannula, and the bilateral common carotid artery cannula should be applied for more than 3 weeks.

Abstract: Objective Particulate matter 2. 5 (PM2. 5) is an important source of air pollution and can cause respiratory and other systemic diseases. Additionally, PM2. 5 can cause cognitive decline, though the exact mechanism is not clear. This study aimed to explore the mechanism by which exposure to environmental PM2. 5 via air pollution induces cognitive impairment. Methods This study used the PM2. 5 online collection and exposure system on C57BL/ 6 mice to make a PM2. 5 exposure mouse model. Mice were exposed for 4 h per day, 5 days per week, for 15 weeks. After the model was established, mouse behavioral symptoms, pathological features and related molecular mechanisms were examined in each group. Results PM2. 5 exposure result ed in pathological changes in lung tissue in mice and exacerbated their cognitive impairment. Immunohistochemical staining of the central nervous system detected microglial cell activation. The level of IL-6 also increased in the central nervous system of exposed mice compared with control mice. PM2. 5 exposure did not cause damage to other major organs in the mice. Conclusions The result suggest that PM2. 5 induced neuroinflammation and promoted the activation of microglial cells in the hippocampus, thus aggravating cognitive impairment in mice.

Abstract: Objective To observe the effect of Fushen recipe on peritoneal function and on peritoneal levels of VEGF, TNF-α, IL-12, and IFN-γ in uremic peritoneal dialysis rats. Methods Fifty male Sprague Dawley rats were divided into 5 groups according to random number table method: normal control, model ( uremic peritoneal dialysis), model + low-dose Fushen recipe intervention, model + high-dose Fushen recipe intervention, and model + celecoxib intervention. A model of uremia was established by 5 / 6 nephrectomy and a peritoneal dialysis model was established by intraperitoneal injection of peritoneal dialysis solution. Peritoneal tissues of rats in each group were collected after continuous administration for 4 weeks. Hematoxylin and eosin staining was used to observe morphological changes of peritoneal tissues, a peritoneal balance test was used to detect peritoneal transport function, and a liquid chip method was used to detect the levels of VEGF, TNF-α, IL-12 and IFN-γ in peritoneal tissues. Results Compared to normal controls, the expression of VEGF and TNF-α in peritoneal tissue of model group rats was up-regulated, and the expression of IL-12 and IFN-γ was down-regulated (P<0.05, P<0.01, respectively). Compared to normal controls, the expression of VEGF and TNF-α was down-regulated and the expression of IL-12 and IFN-γ was up-regulated in the low-dose Fushen recipe group (P< 0.05, P< 0.01, respectively). The expression of VEGF, IL-12, and IFN-γ in the high-dose group and the celecoxib group was down-regulated (P<0.01). Conclusions Fushen recipe can alleviate peritoneal injury and improve peritoneal ultrafiltration function in uremic peritoneal dialysis rats, which may be related to down-regulation of VEGF and TNF-α, and up-regulation of IL-12 and IFN-γ, which are angiogenesis promoting factors in peritoneal tissue.

Abstract: Objective To establish Prpf40b knockout rats for biological research of the gene and explore the effect of gene deletion on development of the heart. Methods Prpf40b knockout rats were established by CRISPR/ Cas9 technology. The genotypes of the founder rats and offspring were identified by sequencing and PCR. The cardiac structure and function of knockout rats were analyzed by ultrasound imaging technology. The microscopic morphology of the rat myocardium was analyzed by histopathological observation. Results PCR and sequencing confirmed successful establishment of Prpf40b gene knockout rats. Compared with the wt rats, ultrasound imaging analysis showed that the cardiac structure and morphology of 2-month-old knockout rats were not significantly abnormal; whereas the ventricular cavity diameter and volume of 12-month-old knockout rats decreased significantly in the systole and diastole, and the ejection fraction decreased significantly. Histopathological analysis showed that the myocardium of 12-month-old knockout rats was arranged irregularly, the thickness of myocardial fibers was uneven, and the sarcoplasmic reticulum was dilated. Conclusions Deletion of the Prpf40b gene induces changes in the overall structure and morphology of the rat heart and abnormal myocardial histology.

Abstract: Objective In this study, we aimed to investigate the effects of different doses of n-butylphthalide (NBP) on cognitive function in db / db mice, the expression of synaptophysin (SYN) and post-synaptic density-95 (PSD- 95) proteins in the hippocampus, as well as mitochondrial structure in the hippocampus. Methods A total of 20 db / db mice were randomly divided into four groups: model group, and low, medium and high-dose treatment groups (five mice in each group). In addition, five normal db / m mice from the same litter were used as the control group. At the age of 6 weeks, db / db mice in the low, medium and high-dose groups were intraperitoneally injected with NBP at a concentration of 20, 40 and 60 mg / kg, respectively, while the control group and the model group were given the same volume of normal saline. Injections were given once a day for 6 weeks. Body weight and fasting blood glucose level were monitored weekly. Morris water maze was used to assess spatial learning and memory abilities. Western blot was used to detect the expression of SYN and PSD-95 in the hippocampus, and the structure of hippocampal mitochondria was observed by electron microscopy. Results Compared with the model group, there was no significant difference in body weight or blood glucose in any treatment group. However, during the water maze exploration period, escape latency was reduced (P< 0. 05), the number of platform crossings was increased (P< 0. 01), protein expression levels of SYN and PSD-95 in the hippocampus were increased (P< 0. 05), and there was a positive relationship between cognitive improvement and protein expression. Under the electron microscope, mitochondrial structure in the control group was normal, the ridge structure was clear and tightly arranged, and the membrane structure was intact. In the model group, mitochondria were damaged, and cristae were sparse, fused and vacuolated. In the treatment groups, most of the mitochondria in the hippocampus were intact, while cristae structure was slightly perturbed, and membrane structure was relatively intact. Conclusions NBP alleviates cognitive dysfunction in db / db mice by regulating the expression of the hippocampal synaptic proteins SYN and PSD-95, and by improving mitochondrial structure. The therapeutic effect in the high dose group was better than that in the low and medium-dose groups.

Abstract: Objective To use intracellular cytokine staining to detect the intensity of the CD8⁺ T cell response and explore the effects of different storage conditions on CD8⁺ T cell activity. Methods Rhesus macaque peripheral blood was collected and peripheral blood mononuclear cells were separated. Some fresh cells were used directly for analysis and the remaining cells were frozen at - 80℃ or in liquid nitrogen and used for analysis after 1 week or 1 year. A positive stimulus was applied and flow cytometry was used to analyze the proportion of living cells, secretion of MIP-1β, TNF-α, IL-2, and IFN-γ, and expression of cell degranulation marker CD107a. Results As the storage time was increased, the cell survival rate decreased, and liquid nitrogen freezing had a higher survival rate than freezing at -80°C. Secretion of MIP-1β and TNF-α from cells cryopreserved for 1 year was significantly higher than that from normal cells and the cell status had changed. The status of cells frozen for 1 week was more similar to fresh cells. Conclusions To maintain low cell death and a normal CD8⁺ T cell response, fresh cells or short-term frozen cells should be used for experiments to measure the level of the CD8⁺ T cell response.

Abstract: Objective To explore the effect of FTY720 on the behavior and monoamine neurotransmitters of post- stroke depression rats. Methods Fifty male SD rats were randomly divided into sham operation, stroke, PSD, FLU, and FLU+FTY720 groups(n= 10 each). The middle cerebral artery thread embolization method was used to establish a focal cerebral ischemia rat model. The PSD rat model was established by combining chronic unpredictable mild stress and isolation method . At 1, 8, 15, 22, and 29 days of stimulation, the behavioral indexes of rats in each group were evaluated. The rats were sacrificed on day 29 and the content of monoamine neurotransmitters and expression of the rate-limiting enzyme of monoamine neurotransmitter synthesis in the hippocampus of rats in each group were analyzed. Results Compared with sham operation and stroke groups, the open field test score and volume ratio of sucrose water consumption of the PSD group were significantly reduced at the same time points ( P< 0. 05). Levels of 5-HT, NE, and DA were significantly reduced in the hippocampus ( P< 0. 05 ). Expression of TPH2 and TH mRNAs was decreased in the hippocampus(P< 0. 05). Compared with the PSD group, the open field test score and volume ratio of sucrose water consumption of FLU and FLU+FTY720 groups were increased at the same time points(P<0. 05). Levels of 5-HT, NE, and DA were increased in the hippocampus(P<0. 05). Expression of TPH2 and TH mRNAs was upregulated in hippocampus(P<0. 05). Conclusions FTY720 improves the depression-like behavior of PSD rats and its effect is related to increasing the levels of monoamine neurotransmitters.

Abstract: Objective To explore the mechanism of bupleurum and scutellaria herb pairs and their effective active compounds and targets in the treatment of sinusitis. Methods The chemical components and their corresponding targets in the bupleurum-scutellaria drug pair were screened through the TCMSP database, and the relevant drug targets screened in the UniProt database and sinusitis disease targets screened in the Genecards database were intersected. The STRING platform was used to construct a target protein interaction action network. The Metascape platform was used to perform GO enrichment analysis and DAVID was used to perform KEGG enrichment analysis. Cytoscape 3. 8. 0 software was used to construct a component-target pathway network diagram and Autodock software was used for molecular docking of key targets and compounds to select the best binding target. Results Thirty-nine related compounds were screened out and the component and disease targets were intersected to obtain 92 targets. The main active components were quercetin, kaempferol, wogonin, baicalein, acacetin, and sitosterol. The core genes were TP53, AKT1, MAPK1, PIK3CG, PTGS2, HSP90AA1, and six others. In molecular docking, the energy of the main active components and major targets was lower than -5 kcal / mol. Conclusions Through network pharmacology and the molecular docking system, the potential effective components and mechanism of bupleurum-scutellaria baicalensis for treatment of sinusitis were identified, which provides a basis for future in-depth research of the mechanism.

Abstract: Objective This study aimed to test the hypothesis that geniposide(GNP) protects against oxidative stress in early bRain injury(EBI)after experimental subarachnoid hemorrhage(SAH). Methods Male Wistar rats(n= 48) were randomly allocated to four groups, including the sham + vehicle group, SAH + vehicle group, SAH +GNP low dose group, and SAH + GNP high dose group. The experimental SAH model was established by injecting blood into the prechiasmatic cistern and treatments were then administered. Outcomes were measured at 24 hours after treatment. The SAH score and mortality rate were calculated. Nuclear factor erythroiD-2-related factor 2(Nrf2)expression in the temporal cortex was detected by immunofluorescence staining. Heme oxygenase-1(HO-1), NADPH quinineoxidoreductase-1(NQO-1), and glutathione S-transferase ( GST ) protein expression in the temporal cortex was determined by western blotting. Malondialdehyde(MDA)levels in the temporal cortex were detected by the thiobarbituric acid method . Apoptosis of nerve cells was determined using TUNEL staining. Results In the SAH+vehicle group, MDA levels and the rate of cellular apoptosis were significantly higher compared with those in the sham+vehicle group( both P<0. 05). The number of Nrf2- positive cells and HO-1, NQO-1, and GST expression were significantly higher in the SAH+vehicle group compared with the sham+vehicle group(all P<0. 05). Compared with the SAH+vehicle group, Ttreatment of either a high or low dose of GNP result ed in a higher number of Nrf2-positive cells and higher HO-1, NQO-1, and GST expression, and lower MDA levels and cellular apoptosis rate(all P<0. 05). In addition, Llower mortality was also observed in the SAH+GNP high dose group. group treated with a high dose of GNP(100 mg / kg). Conclusions GNP exerts a protective effect against oxidative stress in EBI after SAH. This effect is probably mediated by activating the Nrf2 pathway and upregulating the downstream of pathway—antioxidants.

Abstract: Objective To investigate the effects of echinacoside ( EA) on mitochondrial injury in rats with depression. Methods Sprague-Dawley rats were divided into five groups of control, EA, model, treatment, and fluoxetine groups. A rat model of depression was constructed with chronic unpredictable mild stress (CUMS). Rats in the treatment group were intraperitoneally injected with EA mg / ( kg·d). The weight of the rats was recorded, and the sugar water preference index was detected to evaluate the behavior of the rats. Hematoxylin and eosin staining was used to detect damage of bRain tissue. Apoptosis of bRain cells was detected by TUNEL assay. The mitochondrial membrane potential was detected by JC-1 method . Serum interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 (inflammatory cytokines) levels were detected by ELISA. Expression of phosphorylated mitochondrial dynamic associated protein (p-Drp1) in the cytoplasm was detected by Western blot. The content of superoxide dismutase, malondialdehyde, and lactate dehydrogenase, which are markers of oxidative stress, was detected by Kits. Results There were no significant differences in the detection index in the EA group compared with the control group. The model group showed weight loss compared with the control group (P< 0. 01). Sugar water preference was lower (P<0. 01), serum levels of the pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-α were higher, and levels of the anti-inflammatory cytokine IL-10 were lower in the EA group than in the control group ( all P< 0. 01). BRain tissue injury was aggravated, p-Drp1 expression was lower ( P< 0. 01), and oxidative stress in bRain tissue was higher in the EA group than in the control group (all P<0. 01). However, the treatment group showed therapeutic effects and the above-mentioned pathological injuries caused by CUMS recovered. Conclusions EA can alleviate mitochondrial injury in rats with CUMS.

Abstract: Objective To investigate the molecular mechanism of mmu-miR-672-5p in regulating apoptosis of placental chorionic trophoblast cells in rat. Methods Apoptosis of placental chorionic trophoblast cells was detected after overexpression or knockdown of mmu-miR-672-5p. After overexpression or knockdown of mmu-miR-672-5p, the expression of genes regulated by mmu-miR-672-5p was detected by RNA-seq. After setting the threshold and knocking down relevant genes by siRNA, the level of placental chorionic trophoblast cell apoptosis was determined. mmu-miR-672-5p targeting particular genes was verified by luciferase reporter assays. After overexpression of the gene of interest, the expression level of cleaved caspase 3 and the level of placental chorionic trophoblast cell apoptosis was determined by western blotting. Results After overexpression of mmu-miR-672-5p, the level of placental chorionic trophoblast cell apoptosis decreased (P< 0. 05). After mmu-miR-672-5p was knocked down, the level of placental chorionic trophoblast cell apoptosis was increased (P< 0. 05). After knockdown or overexpression of mmu-miR-672-5p, high-throughput sequencing reveled the differential regulation of multiple genes in placental chorionic trophoblast cells, including Zfp229、Zfp503、Slc4a5、Stk24、 Tmem106b、Bax、Adgrb3、Tmem63b、Pmp22、Mroh2a、Dsn1、Pramef25、Naaladl2、Clk2、 Stx16、Usp28、Clint1、 Jph4、Msl2、 Krtap8-1、Pkp2、Mllt3、Rai14 After knocking down the above genes, only knockdown of Bax caused a decrease in the level of placental chorionic trophoblast cell apoptosis (P<0. 05). After overexpression of Bax, the level of cleaved caspase 3 and the level of the placental chorionic trophoblast cell apoptosis increased (P<0. 05). After overexpression of mmu-miR-672- 5p, both the mRNA and protein levels of Bax decreased (P< 0. 05). After mmu-miR-672-5p was knocked down, both mRNA and protein levels of Bax increased (P<0. 05). In addition, mmu-miR-672-5p targeted the 3′-non-coding region of Bax (P<0. 05). After simultaneous overexpression of mmu-miR-672-5p and Bax, there was no significant change in the level of placental chorionic trophoblast cell apoptosis (P> 0. 05). After simultaneously knocking down mmu-miR-672-5p and Bax, there was no significant change in the level of placental chorionic trophoblast cell apoptosis ( P> 0. 05). Conclusions mmu-miR-672-5p decreased Bax expression by targeting its 3′-non-coding region, and subsequently inhibited the apoptosis of placental chorionic trophoblast cells.

Abstract: Objective To summarize popular stimulation factors, model duration, and main behavioral tests used in the chronic unpredicted mild stress (CUMS) model of depression, so as to provide a reference for the use of CUMS in depression research. Methods Literature related to CUMS models from the past 10 years was searched for in PubMed databases and screened according to certain criteria. The animals, stressors, and duration of CUMS models were summarized. Results Male rats are most often used in CUMS models. Seven to nine stressors should be chosen for an experiment and should not be repeated within 3-7 days. Among the stimulation factors, deprivation of food or water, damp bedding, cold water swimming, tilt cages, and changes in light rhythm are recommended. Three to four weeks are recommended for the model duration. Behavioral tests included sucrose preference test, open field test and force swimming test. Conclusions This study provides a useful reference for the use of CUMS in models of depression regarding the animals, stimulation factors, and model duration.

Abstract: Objective To investigate the effect of daphnetin on the TRL4 / NF-κB signaling pathway involved in nerve regeneration and functional recovery after spinal cord injury ( SCI) in rats. This study aimed to provide a basis for study of the molecular mechanism of SCI. Methods A laminectomy was performed at the T9 level and the exposed dorsal surface of the spinal cord was subjected to a contusion injury as established a spinal cord injury model. On the 1st, 8th, 14th, 21st, and 30th days after the operation, the Basso Beattie Bresnahan motor function score and combine behavioral score were used to evaluate neurological function of rats with SCI in each group. The activity of SOD, CAT, and GSH PX enzymes, and MDA, TNF-α, IL-1β, IL-6, and IL-10 expression were detected by Kits. Western blotting was used to determine protein levels of Bax, Bcl-2, caspase-3, Cyt-C, BDNF, TrkB, and p-TrkB in the spinal cord tissue of experimental rats. Results The BBB and CBS scores were significantly improved by daphnetin (P<0. 05), and the effect of the high daphnetin group was better than that in the low daphnetin group. Additionally, daphnetin improved the activity of SOD, CAT, and GSH PX and MDA levels in the spinal cord of experimental rats (P<0. 05), and reduced TNF-α, IL-1β, IL-6, and IL-10 levels in the spinal cord (P<0. 05). Western blot showed that daphnetin significantly regulated abnormal expression of apoptosis-related proteins and the BDNF/ TrkB signaling pathway. Conclusions Daphnetin may play a role in spinal cord injury by activating TRL4 / NF-κB signaling.

Abstract: Objective To establish a human SNCA whole-bRain transgenic mouse model, and to obtain preliminarily data on the role of α-synuclein in the central nervous system. Methods rAAV2 / 9 (1 × 10¹³ genome copies (GC) / mL) carrying either human SNCA-EGFP or EGFP was bilateral injected intracerebroventricularly in mice at postnatal day 0. The expression pattern and subcellular localization of α-synuclein was examined at 2 weeks and 3 months of age by immunofluorescence and Western blot. Glial profile and pathological changes were analyzed by immunofluorescence and immunohistochemical staining. Results hSNCA transgenic mice were successfully constructed, and α-synuclein was widely expressed throughout the brain, with high expression in the olfactory bulb, cerebral cortex, hippocampus, interbrain and midbrain. Furthermore, nuclear α-synuclein was detected in the olfactory bulb, cerebral cortex, CA2 / 3 of the hippocampus and Purkinje cells of the cerebellum. Overexpression of α-synuclein caused the proliferation of astrocytes and microglia. In addition, pS129 and aggregation of α-synuclein were observed in the olfactory bulb and cerebral cortex. Conclusions hSNCA whole-bRain transgenic mouse model was established successfully, with high long-term expression of α-synuclein and enhanced gliosis and α-synuclein pathology. This model should be useful for studying the physiological function of α-synuclein and its role in Parkinson’s disease.

Abstract: Objective To examine the mechanism of the eye-open at birth (EOB) phenotype in B6-Co mice at birth. Methods C57BL/ 6 (B6) mice were bred at a ratio of male to female mice of 2 ∶1 to obtain pregnant mice. B6-Co mice were bred by B6 (male) mice with B6-Co (female) mice at a ratio of 1 ∶2 or B6 (female) mice with B6-Co (male) mice at a ratio of 2 ∶ 1 hybridization to obtain pregnant mice. We selected 18. 5-day embryos of pregnant mice and then collected embryonic eyelid tissue to culture mouse eyelid fibroblasts. We used immunofluorescence and hematoxylin and eosin staining to identify primary cells and observe morphology of fibroblasts. The difference in growth curves between two cell types was observed using the direct counting method with a hemocytometer. Real-time PCR and Western blot were used to detect HSP70 expression in the two cell types. Lipofectamin2000 was used to transfect the fibroblasts.The HSP70 gene mRNA and protein expression levels were detected by Real-Time PCR and Western blot to determine the interference efficiency. The migration ability of fibroblasts was detected by Transwell experiment. Results The growth curve of eyelid fibroblasts showed that B6-Co mouse eyelid fibroblasts proliferated more slowly than B6 mouse eyelid fibroblasts ( P< 0. 01). However, HSP70 expression levels in B6-Co mouse fibroblasts were significantly lower than those in B6 mouse fibroblasts. After the fibroblasts were transfected with HSP70 siRNA interference vector, the expression levels of HSP70 gene on mRNA and protein were effectively inhibited. Among them, siRNA-HSP70 - 3 has the strongest interference efficiency, and the interference efficiency was up to 70% (P< 0. 05). The migration abilities of fibroblasts in the siRNA- HSP70 group were significantly lower (P< 0. 05) than those in the siRNA -NC group. Conclusions Downregulation of HSP70 gene and protein expression affects the growth curve of fibroblasts in B6-Co mice and may be involved in regulation of embryonic development of fibroblasts. The constructed siRNA-HSP70- 3 interference vector can effectively inhibit the expression of target gene HSP70 on fibroblasts, and can significantly inhibit the cell migration. This could be one of the important reasons for the EOB phenotype of B6-Co mice.

Abstract: Objective NOBOX is a transcription factor that plays a key role in the activation of primary follicles. It directly regulates the transcription of Gdf9 and participates in the GDF9 / SMAD pathway to affect the proliferation and differentiation of granulosa cells. Kit, an important gene affecting follicular development, has multiple NOBOX binding sites in its promoter. In this study, we aimed to investigate the transcriptional regulation of Kit by the transcription factor NOBOX in the primary follicular development stage as well as the influence of the GDF9 / SMAD pathway on follicular development. Methods The development time of primary follicles in vitro was measured. qRT-PCR was used to detect the mRNA expression changes of Nobox, Kit, Kitl and Gdf9 in primary follicles injected with Nobox-siRNA. Western blot was used to measure protein expression changes for NOBOX, Kit and P-SMAD in primary follicles injected with Nobox-siRNA. ChIP assay was used to identify the binding site of NOBOX on the Kit gene promoter. Results Primary follicles developed into secondary follicles on the 5th day in vitro. Injection of Nobox-siRNA into primary follicles delayed their development into secondary follicles by 2 days. After Nobox-siRNA injection into primary follicles, the expression of Nobox, Kit, Kitl and Gdf9 mRNAs in follicles was significantly downregulated, and the expression levels of NOBOX, Kit and P-SMAD2 / 3 proteins were decreased. NOBOX showed binding to the Kit gene promoter. Conclusions NOBOX is a key gene in the development of primary follicles to secondary follicles in mice. NOBOX directly binds to the Kit gene promoter and affects the KitL/ Kit and GDF9 / SMAD pathways in primary follicles.

Abstract: Objective To investigate the effect of sacubitril / valsartan on myocardial injury and cardiac remodeling in rats with heart failure, and to investigate its regulatory effect on transforming growth factor-β1 (TGF-β1) / Smad3 and nuclear factor-κB (NF-κB) signaling pathways. Methods An animal model of heart failure was induced by ligation of the left anterior descending coronary artery in rats. After modelling, rats were treated daily with sacubitril / valsartan at 10 mg / kg (sacubitril / valsartan group, n= 15). Rats in the sham group (n= 15) and the model group (n= 15) were treated with an equal volume of normal saline. Rats were treated for 4 weeks. Echocardiography and histology were used to assess heart function and fibrosis, respectively. Protein levels of TGF-β1, phosphorylated Smad3, phosphorylated Smad7, collagen I, alpha smooth muscle actin, tumor necrosis factor-α, interleukiN-6, NF-κB, and phosphorylated κBα were determined by western blot analysis. Results Left ventricular ejection fraction ( EF) and left ventricular fraction shortening (FS) in the sacubitril / valsartan group were significantly higher, while LVIDs and LVIDd in the sacubitril / valsartan group were significantly lower compared with those in the model group (P< 0. 05). Collagen I expression was significantly reduced in the sacubitril / valsartan group compared with the model group ( P< 0. 05 ). TGF-β1 protein expression and Smad3 phosphorylation levels in the sacubitril / valsartan group were significantly lower, while Smad7 phosphorylation levels were significantly higher compared with the model group (all P<0. 05). Tumor necrosis factor-α and interleukiN-6 protein expression was significantly reduced in the sacubitril / valsartan group compared with the model group ( both P<0. 05). NF-κBp65 and phosphorylated κBα protein expression was significantly reduced in the sacubitril / valsartan group compared with the model group (both P<0. 05). Conclusions Sacubitril / valsartan inhibits myocardial fibrosis and the inflammatory response by inhibiting TGF-β1 / Smad3 and NF-κB signaling pathways in rats with heart failure.

Abstract:Diabetes mellitus is a metabolic disease that is characterized by high blood sugar levels. Chronic hyperglycemia in diabetes leads to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels, and nerves. These complications often threaten the life of patients. Therefore, there is an urgent requirement for safe and effective drugs to intervene in diabetic complications. Astragali radix is a common tonic in Chinese medicine and one of the main components of many anti-diabetes treatments using Chinese herbal compounds. Astragali radix is rich in polysaccharides (APS), saponins (ASS), flavones (ASF), and other anti-diabetes components, which have a good effect on the complications of diabetes. In this article, literature on the complications and mechanism of Astragali radix for intervention in diabetes in recent years is reviewed to provide a reference for future studies on complications of intervention by Astragali radix in diabetes.

Abstract:As a complex microecosystem, the gut microbiota has a close relationship with the host and plays a central role in regulating physiological functions related to nutrition, immune system activation and host defense. Tryptophan (TRP), an essential amino acid, must be obtained from the diet. TRP participates in a variety of physiological functions and affects the growth and health of the human body. Abnormal TRP metabolism has been associated with many diseases. One of the main ways in which the gut microbiota interacts with the host is through metabolites. Tryptophan catabolites produced by gut microbiota are important signaling molecules in the microbial community and in host-microbe crosstalk, and play an important role in physiological and pathological processes. This study describes research progress on the classification and function of gut microbiota, the influence of gut microbiota on TRP metabolic pathways and related diseases, and the potential mechanism of these effects, and discusses new clinical research for disease pathogenesis and treatments.

Abstract:Atherosclerosis (AS) is a chronic disease characterized by lipid deposits in blood vessels. An increasing number of studies suggest that immune-mediated inflammatory responses play an important role in the pathogenesis of AS. Toll-like receptor 4 (TLR4) participates in various stages of AS as a member of the natural immune pattern recognition receptor family, and thus has become an important target for the treatment of AS. This article reviews the progress in research regarding TLR4 and AS.

Abstract:Angiogenesis is closely related to many diseases and plays an important role in the development and prognosis of diseases. Long non-coding RNAs ( lncRNAs) are important regulatory molecules of angiogenesis that are involved in the pathological recovery process of ischemic stroke, tumor, atherosclerosis and other diseases by regulating the phenotypic transformation of vascular endothelial cells, angiogenic factors and miRNA expression. Here, we review the biological functions of lncRNAs, and describe their expression and regulatory effects in angiogenesis and vascular diseases to provide reference for ongoing research into lncRNA mechanisms of action and their clinical application in angiogenesis.

Abstract:Rabbits and primates have similar evolutionary history and vascular morphological characteristics similar to humans. In addition, rabbits are very sensitive to cholesterol overload. After eating a high cholesterol diet, hypercholesterolemia can be formed in a short time. Therefore, rabbits have unique advantages to establish atherosclerosis models rapidly and concisely. Many method establish rabbit as animal models, including the traditional high-fat diet feeding method , the femoral artery balloon injury combined with high-fat diet feeding, CRISPR/ Cas9 gene editing technology and other emerging modeling method . In this paper, we review the establishment method and advantages and disadvantages of rabbit as models commonly used and emerging in recent years.