Model Control Group Research Articles

Protective effect of crocin on chronic heart failure and its mechanism of action

Purpose: To explore the mechanism of action of crocin in rat chronic heart failure (CHF).
 Methods: One hundred male Sprague Dawley (SD) rats were used to establish CHF rat model by the abdominal aorta constriction method. They were equally randomized into either the model control group (injected with distilled water), crocin low, medium, and high dose groups (daily administered 0.05, 0.1, and 0.75 g/kg of crocin, respectively), or positive control group (daily administration of benazepril hydrochloride), and normal control (without treatment). Parameters evaluated include heart function, inflammatory index changes, and oxidative stress damage.
 Results: The crocin low, medium, and high dose groups and the positive control group had significantly better cardiac function indices versus the model control group (p < 0.05). High-dose crocin resulted in significantly lower levels of inflammatory factors than a low or medium dose (p < 0.05). Rats that received a medium or high dose of crocin showed significantly increased activity of myocardial antioxidant enzymes, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) content when compared to those given low doses of crocin (p < 0.05). Protein expressions of Bax-activated caspase-3, and NF-kB decreased significantly with increase in crocin dosage. A high dose of crocin produced a significantly lower apoptotic rate of cardiomyocytes, sodium–calcium exchanger (NCX) level and higher content of sarcoplasmic reticulum calcium pump 2a (SERCA2a) compared with low- and medium-doses.
 Conclusion: Crocin protects myocardial tissue and enhances ventricular diastolic function of CHF rats through down-regulation of NCX expression and up-regulation of SERCA2a expression. Further studies using clinical CHF models to categorize and analyze crocin-related cellular pathways will be required.

Research on the mechanism of prednisone in the treatment of ITP via VIP/PACAP-mediated intestinal immune dysfunction

RationaleImmune thrombocytopenia (ITP) is thought to be a result of immune dysfunction, which is treated by glucocorticoids such as prednisone. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have immunomodulatory properties, but their role in intestinal immune control is unclear. The major goal of this study was to look at the effects of prednisone on platelet, VIP, and PACAP levels in ITP mice, as well as the regulatory system that controls intestinal immunity.MethodsEighteen BALB/c mice were randomly divided into three groups: blank control group, model control group, and prednisone group, with six mice in each group. The ITP animal model control group and the prednisone group were injected with anti-platelet serum (APS) to replicate the ITP animal model. The prednisone group began prednisone intervention on the 8th day. Platelet count was dynamically measured before APS injection, on the 4th day of injection, on the 1st day of administration, on the 4th day of administration, and at the end of the experiment. After the experiment, the expression of p53 protein in mouse mesenteric lymph node lymphocytes was detected by immunohistochemistry. The changes in lymphocyte apoptosis rate in mouse mesenteric lymph nodes were detected by in situ terminal transferase labeling (TUNEL). The contents of VIP and PACAP in the mouse brain, colon, and serum were detected by enzyme-linked immunosorbent assay (ELISA). The contents of IFN-γ, IL-4, IL-10, IL-17A in the mouse spleen were detected by ELISA.Results①Changes of peripheral platelet count: there was no significant difference in platelet count among the three groups before modeling; on the 4th day, the platelet count decreased in the model control group and prednisone group; on the 8th day, the number of platelets in model control group and prednisone group was at the lowest level; on the 12th day, the platelet count in prednisone group recovered significantly; on the 15th day, the platelet count in prednisone group continued to rise. ②Changes of VIP, PACAP: compared with the blank control group, VIP and PACAP in the model control group decreased significantly in the brain, colon, and serum. Compared with the model control group, the levels of VIP and PACAP in the brain, colon, and serum in the prednisone group were increased except for serum PACAP. ③Changes of mesenteric lymphocytes: the expression of p53 protein in the mesenteric lymph nodes of model control group mice was significantly higher than that of blank control group mice. After prednisone intervention, the expression of p53 protein decreased significantly.④Changes of cytokines in spleen: compared with blank control group, IFN- γ, IL-17A increased and IL-4 and IL-10 decreased in model control group. After prednisone intervention, IFN- γ, IL-17A was down-regulated and IL-4 and IL-10 were upregulated.ConclusionsPrednisone-upregulated VIP and PACAP levels decreased P53 protein expression and apoptosis rate in mesenteric lymph node lymphocytes and affected cytokine expression in ITP model mice. Therefore, we speculate that the regulation of intestinal immune function may be a potential mechanism of prednisone in treating ITP.

Polysaccharide from fermented mycelium of Inonotus obliquus attenuates the ulcerative colitis and adjusts the gut microbiota in mice

Ulcerative colitis (UC) is a disease characterized by chronic inflammation of the colon. Polysaccharides not only have biological activities but also can regulate gut microbiota to alleviate the symptoms of UC. In this study, polysaccharide extracted from mycelium of Inonotus obliquus (IOP) was prescribed to treat UC induced by dextran sodium sulfate (DSS) in mice. Compared to model control group (MC), IOP-Low, IOP-Medium and IOP-High (IOP-L, IOP-M and IOP-H) treatment groups increased the body weight rate by 6.0%–9.6%, colon length by 8.57%–25.14% and superoxide dismutase (SOD) activity by 53.8–110.4 U/mg, while decreased the malondialdehyde (MDA) content by 37.4%–64.8%, myeloperoxidase (MPO) activity by 29.0%–46.9%, and the concentration of nitric oxide (NO) by 24.8–35.6 μmol/L. IOP treatment also promoted the secretion of interleukin (IL)-10 but suppressed those of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Simultaneously, analysis of high-throughput sequencing indicated that IOP reduced the ratio of Firmicutes to Bacteroidetes (F/B) at phylum level, and increased the relative abundance of Bacteroides and Lactobacillus at genus level. In brief, IOP may be a promising alternative medicine for UC remedy by regulating the anti-inflammatory level, the anti-oxidative ability and the gut microbiota composition.

Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Efficiency of Chinese medicine Bushen Huatan formula for treatment of polycystic ovary syndrome in mice via regulating gut microbiota and PPARγ pathway.

To explore the effect and mechanism of Chinese medicine Bushen Huatan formula in treatment of polycystic ovary syndrome (PCOS). Twenty-four SPF female C57BL/6J mice were randomly divided into 3 groups with 8 animals in each group. Control group was given drinking water ad libitum; PCOS was induced by giving letrozole gavage and high-fat diet in model group and treatment group; treatment group received Bushen Huatan formula suspension for 35 d. The sex hormone levels of mice were detected by enzyme-linked immunosorbent assay. Ovary morphology was observed under light microscope after hematoxylin and eosin staining. The feces in the colon of mice were collected, and the gut microbiota was detected by 16S rRNA sequencing. The short chain fatty acids were detected by gas chromatography-mas spectrometry. The expression of peroxisome proliferator activated receptor (PPARγ) was detected by immunohistochemistry. The mRNA expression of mucin-2, occludin-1, tight junction protein zonula occludens 1 (ZO-1) and PPARγ in intestinal epithelium were detected by realtime RT-PCR. The expression of inducible nitric oxide synthase (iNOS) and PPARγ was detected by Western blotting. Compared with the control group, the body weight, serum levels of follicle stimulating hormone, luteinizing hormone and testosterone in the model group were increased, and serum levels of estradiol were decreased (all P<0.01); the ovarian structure under light microscope was consistent with the characteristics of PCOS. Compared with the model group, the serum levels of sex hormone and ovarian structure in treatment group were improved. The overall structure of gut microbiota in PCOS model mice changed. Compared with control group, there were significantly reduced abundance of Firmicutes, and increased abundance of Verrucomicrobia, Proteobacteria and Actinobacteria inthe model group at phylum level (all P<0.05); there were significantly reduced abundance of Lactobacillus, and increased abundance of Akkermansia, Lachnoclostridium, Lactococcus and Eubacterium_coprostanoligenes at genus level (all P<0.05). The disordered condition of gut microbiota was significantly improved in treatment group. Compared with control group, the contents of acetic acid, propionic acid and butyric acid in feces of model group were significantly decreased (all P<0.05); while the contents of propionic acid and butyric acid in treatment group were significantly increased compared with model control group (both P<0.05). Compared with control group, the mRNA expression of ZO-1 and protein expression of iNOS in model group were significantly increased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were significantly decreased (all P<0.05). Compared with model group, the mRNA expression of ZO-1 and protein expression of iNOS in treatment group were decreased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were increased. PCOS induced by letrozole high-fat diet induces microflora imbalance in mice. Chinese medicine Bushen Huatan formula may increase the level of short chain fatty acid by regulating gut microbiota, thereby activating the intestinal PPARγ pathway and improving intestinal barrier function to act as a cure for PCOS.

Effects of Coix seed extract, Lactobacillus paracasei K56, and their combination on the glycolipid metabolism in obese mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism through different modes of action. We tested the effects of CSE, Lactobacillus paracasei K56, and their combination to determine whether they have synergistic effects on glycolipid metabolism of obese mice. We fed male C57BL/6J mice with high-fat diet for 8 weeks to establish an obesity model. The obesity mice were selected and divided into five groups: the model control group and four intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31-4.41g, vs. HFD 42.25g, p<0.01), and epididymal (lower about 0.58-0.92g, vs. HFD 2.50g, p<0.01) and perirenal fat content (lower about 0.24-0.42g, vs. HFD 0.88g, p<0.05); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. K56+CSE-combined intervention groups were more effective in lowering blood glucose, IL-1β, and TNF-α levels than the CSE and K56 alone interventions. The content of fatty acid synthase and SREBP-1c protein in liver tissue was lower. The combination has synergistic effects on weight control, fat reduction, and blood glucose regulation by improving the chronic inflammatory state and reducing the content of lipid synthesis-related enzymes of obese mice, which can hinder chronic disease progression. PRACTICAL APPLICATION: Coix seed extract can be used in obese people to regulate abnormal glucose and lipid metabolism and delay the development of chronic diseases.

Effects of Atractylodes Macrocephala Rhizoma polysaccharide on intestinal microbiota composition in rats with mammary gland hyperplasia.

In recent years, mammary gland hyperplasia (MGH) has been considered to be one of the diseases caused by endocrine disorders. It has been shown that diseases caused by endocrine disorders can be treated by regulating intestinal microbial. As a commonly used medicine in clinical practice, Atractylodes Macrocephala Rhizoma has good functions in regulating intestinal homeostasis. Therefore, this paper studied the effect of Atractylodes Macrocephala Rhizoma polysaccharide (AMP) on the intestinal flora of MGH rats, providing a new idea for polysaccharide treatment of MGH. Eighteen female SD rats were selected and randomly divided into three groups: blank control group (Con), model control group (Mod), and AMP group, six rats in each group. MGH rat models were established by estradiol-progesterone combination and treated with AMP gastric infusion. The levels of E2, P, and PRL in the serum of rats were measured, the intestinal contents were collected, and 16s rRNA high- throughput sequencing technology was analyzed the changes of intestinal flora in the MGH rats. AMP has good therapeutic effects on MGH rats, decreasing estradiol (E2) and prolactin (PRL) levels and increasing progesterone (P) levels; at the same time, it can regulate the abundance and diversity of intestinal flora of MGH rats, improve the disorder of intestinal flora caused by MGH, and change the community structure, increase the abundance of beneficial flora, and decrease the abundance of pathogenic flora. AMP can improve the intestinal microbiological environment of MGH rats, maintain the microecological balance of intestinal microbial, and improve MGH symptoms.

The effect of Kuntai capsule on ovarian function in cisplatin-induced premature ovarian insufficiency rats.

This study aims to evaluate the effect of Kuntai capsule on ovarian function in cisplatin-induced premature ovarian insufficiency rats and to explore the mechanism of Kuntai capsule on the ovarian function of rats. Seventy-four female Sprague-Dawley rats were used for this study. Eight of the rats were randomly assigned to the Control group. The remaining sixty-six rats were utilized to establish the POI model via Cisplatin and then randomly divided into four groups: the model Control group, the Estradiol group, and groups treated with low and high doses of Kuntai capsule. For the 28-day administration, the Control and model Control groups were intragastrically administered with 2.0 mL of 0.9% sodium chloride daily, the Estradiol group with 2.0 mL of Estradiol suspension (0.2mg/kg/d), and the low dose Kuntai capsule group and the high dose Kuntai capsule group with 2.0 mL of Kuntai capsule suspension (0.6g/kg/d, 1.8g/kg/d, respectively). Sex hormone levels, estrous cycle, and ovarian coefficient of the five groups were compared, histological sections analyzed follicle counts, and the protein expressions of growth differentiation factor 9, light chain 3 A-II, and Beclin 1 in the ovarian tissue were detected by Western blotting. After the 28-day administration, the serum Estradiol and Follicle-Stimulating Hormone levels of the group treated with low dose of Kuntai capsule were not significantly different from the Control group, the serum anti-Müllerian Hormone level of the group treated with high dose of Kuntai capsule was significantly higher than the Estradiol group. The estrous cycle of the group treated with low dose of Kuntai capsule was significantly lower than the model Control group. Regarding ovarian coefficient, resting and growing follicles, growth differentiation factor 9, light chain 3 A-II, and Beclin 1 expression, both Kuntai capsule groups outperformed the model Control group with the statistical difference (P<0.05). Kuntai capsule can improve the estrous cycle and ovarian coefficient of rats with premature ovarian insufficiency, maintain the number of resting and growing follicles, and up-regulate the protein expression of growth differentiation factor 9, light chain 3 A-II, and Beclin 1 of rats' ovaries.

PLATELET SUPPRESSION BY TIROFIBAN AMELIORATES PULMONARY COAGULATION AND FIBRINOLYSIS ABNORMALITIES IN THE LUNGS OF MOUSE ANTIBODY-MEDIATED TRANSFUSION-RELATED ACUTE LUNG INJURY.

This study aimed to explore the ameliorating effects of the platelet surface glycoprotein IIb/IIIa receptor antagonist tirofiban on coagulation and fibrinolytic abnormalities in a mouse model of antibody-mediated transfusion-associated acute lung injury (ALI). This is important because ALI is a major cause of death attributable to the occurrence of adverse transfusion reactions. No information on a definite diagnosis or pathological mechanism exists, and targeted treatment options are not available. In this study, wild-type male Balb/c mice aged 8 to 10 weeks were randomly divided into the TRALI model, blank control, tirofiban intervention, and isotype control groups. After different treatment exposures, the mice were observed for 2 h before being killed, and lung tissue samples were collected. To explore the intervention effect of tirofiban, the degree of lung injury was quantified by estimating the lung wet/dry ratio, rectal temperature, survival rate, total protein, and myeloperoxidase and via hematoxylin-eosin staining. Furthermore, the coagulation, anticoagulation, and fibrinolysis assays were measured by automatic coagulation instrument and enzyme-linked immunosorbent assay kits, and the fluorescence densities of platelets and fibrin were quantified using immunofluorescence to analyze the effects of tirofiban on the platelet and fibrin interactions of TRALI. Compared with the TRALI model group, the lung injury indices in the tirofiban intervention group decreased significantly, and survival rates also improved. Furthermore, the level of coagulation and fibrinolytic abnormalities were obviously lower than those in the TRALI model group. In conclusion, our findings suggest that tirofiban might interfere with TRALI by inhibiting platelet activation and improving coagulation and fibrinolytic abnormalities.

Effects of acupuncture on angiogenesis-associated factor expression in ischemic brain tissue following cerebral infarction in rats

Background: We aimed to investigate changes into the levels of angiogenesis-associated factors following cerebral infarction and acupuncture intervention and reveal the underlying molecular mechanisms involved in promoting angiogenesis. Methods: Model rats with middle cerebral artery occlusion (MCAO) were randomized into electroacupuncture (EA), model control (MC), and blank control (control) groups. Changes in the degree of neurological impairment following cerebral infarction and angiogenesis in the ischemic center and peripheral area were observed using immunofluorescence double-labeling. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect changes in the Ang-1, Ang-2, PDGF-B, and bFGF levels. Moreover, the effects of EA intervention were evaluated. Results: The neurological severity score of each phase in the EA group was lower than that into the simultaneous phase in the MC group. The proliferation of vascular endothelial cells in the EA group was higher than that in the MC group at 12 hours to 7 days. The Ang-1 and Ang-2 mRNA and protein levels in the EA group were significantly higher than those in the MC group. PDGF-B levels in the EA group were significantly higher than those in the MC group at 3 to 6 hours and 3 to 12 days, and protein levels were high at 6 hours and 3 to 12 days. bFGF mRNA levels at 24 hours to 12 days and bFGF protein at 3 to 12 days were significantly elevated in the EA group than those in the MC group. Conclusions: EA at Shui Gou(DU 26) significantly improved the neurological symptoms of MCAO rats, promoted vascular endothelial cell proliferative activity around the infarct area, significantly advanced the time of proliferation of vascular endothelial cells, and upregulated the expression of angiogenesis-related factors, thereby promoting angiogenesis. Thus, EA may significantly improve the prognosis of cerebral infarction. Graphical abstract: http://links.lww.com/AHM/A43.

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model.

We assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites. An acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment. HJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites. This work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

Antifatigue Effect of Asiaticoside in Mice by Attenuating Oxidative Stress.

Asiaticoside is one of the main components of triterpenoid saponins extracted from Centella asiatica. Asiaticoside has shown the effects of wound healing, osteoclastogenesis, anti-inflammatory, anti-cancer, and improving cognition in multiple human disease models. However, studies on the antifatigue effects of asiaticoside have not been explored. Therefore, the aim of this study was to investigate the potential antifatigue effect and underlying mechanism of asiaticoside administration on exhaustive exercise performance. Male Kunming mice were divided into four groups randomly (n = 20/group). Saline (10 mL/kg) was administered to the model control group and the other three experimental groups were fed with low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) asiaticoside once/daily for 14 days. The antifatigue effect of asiaticoside on mice was estimated by analyzing changes in body weight, weight-loaded swimming time, rotating time, lactic acid, urea nitrogen, liver/muscle glycogen, serumal superoxide dismutase, superoxide dismutase and the liver tissues of hematoxylin and eosin (H&E) staining. The results indicated that no significant differences were observed in the body weight of each group (p > 0.05). Compared with the model control group, supplementation of asiaticoside significantly prolonged the weight-loaded swimming time and rotating time; Decreased the blood lactic acid (LA), blood urea nitrogen (BUN), and serumal malonaldehyde (MDA); And increased the content of liver/muscle glycogen and serumal superoxide dismutase levels (SOD) (p < 0.05). Furthermore, the pathological results of the liver were improved greatly. The maximal effect was observed in the medium group of 20 mg/kg. Asiaticoside is capable of reducing the fatigue effect by regulating energy consumption, energy metabolism and improving antioxidant activity after exercise. While there are still some shortcomings in this study, our findings provide a scientific basis for developing an asiaticoside-based antifatigue supplement.

The Antidepressant Mechanism of JiaWeiWenDan Decoction Regulating p38MAPK-ERK5 Signal Transduction Pathway

Objective: To investigate the anti-depression mechanism of JiaWeiWenDan Decoction in regulating p38MAPK-ERK5 signal transduction pathway. Methods: Depression model rats were randomly divided into Blank Control Group, Model Control Group, Chinese Medicine Treatment Group, and Western Medicine Treatment Group (hereinafter referred to as Blank Group, Model Group, Chinese Medicine Group, and Western Medicine Group), with 48 rats in each group. The mice were treated with p38MAPK-ERK5 on the 7th day, 14th day and 21st day, respectively, and the mice were treated for 28 days. The key targets and cytokines in p38MAPK-ERK5 signal transduction pathway were detected. Results: Compared with the Blank Group, the expression of p38MAPKmRNA in the hippocampus of the Model Group was increased. The Chinese Medicine Group and Western Medicine Group could reduce the expression of p38MAPK mRNA (P P P P < 0.05); There was no significant difference between the Chinese and Western Medicine Groups. Conclusion: The anti-inflammatory effect of JiaWeiWenDan Decoction may be related to the regulation of p38MAPK-ERK5 signaling pathway. With the advance of the treatment week, the best effect was obtained when the treatment was started on the 7th day of modeling.

MiR-141-Modified Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits the Progression of Severe Acute Pancreatitis

The therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on severe acute pancreatitis (SAP) and miRNAs are currently the research hotspots. This study intends to explore the potential impact of miR-141-modified BMSCs on SAP. After establishment of rat model of SAP, the animals were grouped into control group, model group, BMSCs group, miR-141 group, positive control group, and PI3K/mTOR signaling agonist group (agonist group) followed by analysis of miR-141 expression by RT-qPCR and the expression of serum amylase, IL-6, TNF-α, TAP, PI3K, mTOR, and LC3-II by Western blot and ELISA. miR-141 was significantly up-regulated in the miR-141-modified BMSCs group (p &gt; 0.05). The contents of serum amylase, IL-6, TNF-α, and TAP was increased in SAP rats and decreased after BMSC treatment (p &gt; 0.05). The increased autophagy flux in the rats with SAT was reduced upon treatment with BMSCs and autophagy flux was decreased in miR-141 group but increased in positive control group. The model and positive control group presented highest expression of LC3-II, p-PI3K and p-mTOR, followed by BMSCs group and miR-141 group (p &lt; 0.05). In conclusion, miR-141-modified BMSCs decrease the phosphorylation of PI3K and mTOR to inhibit PI3K/mTOR signaling activity and downregulate LC3-II protein to inhibit autophagy, thereby ameliorating the development of SAP, indicating that miR-141 might be a therapeutic target for SAP.

The Effectiveness of Role-play Integrated Multisensory Learning to Enhance Students' Confidence and Speaking Skill

Lack of self-confidence and speaking abilities can hinder student learning. Students without self-confidence struggle to express their views and opinions, resulting in poor speaking skills. This study examines whether Role-play Integrated Multisensory Learning (RIML) boosts students' self-confidence and speaking skills. This quantitative experimental study uses an explanatory model and non-equivalent control group design. This study included 30 control and 30 experimental students. Grade 1 elementary school 93 Kendari State Elementary School children were purposively sampled for the study. This study collected data using observation. In this study, students' confidence and speaking skills in five were measured in four ways. This study analyzed data using normality and homogeneity tests. Additionally, SPSS with an independent sample t-test was used to assess the data. Participants' self-confidence and speaking skills improved significantly after the Role-play Integrated Multisensory Learning (RIML) intervention. The experimental group had a high average score of 5,9.0, rising to 91.3 on student confidence and 83.2 on student speaking skills. Additionally, the significance value for each variable is 0.000 &lt;0.05. The findings in this study indicate an improvement in elementary school students' confidence and speaking abilities after receiving an intervention in the form of Role-play Integrated Multisensory Learning (RIML).RIML learning uses all senses in roleplay learning to assist students in understanding the context of learning and practicing speaking skills to gain confidence. Future studies may integrate multisensory features into other learning approaches to stimulate students with varied learning styles.

Synergistic Effect of Yemeni Sesame Oil and Squalene on Hyperlipidemia-induced Reproductive Damage in Male Rats

This study was purposed to explore the synergistic amelioration effect and optimal feeding time of sesame oil and squalene on hyperlipemia-induced sexual dysfunction rats. We established the hyperlipidemia-induced reproductive damage model, the three groups of test substances (sesame oil, a mixture of sesame oil and squalene, and sildenafil) were orally administrated to those hyperlipidemic rats on day 30 and day 60. The results showed that compared with the pure sesame oil, the mixture of sesame oil and squalene can synergistically decrease concentration levels of TG, TC, and LDL-C, significantly increasing the serum testosterone level and sperm count of the epididymal tail, which the 30 days’ effect was better than the day 60. Compared with the model control (MC) group, the Organ Coefficient of penile increased significantly in the sesame oil (SO), sesame oil+ Squalene (SOS), and Sildenafil (SN) group, and no pathological changes were found in the penile and testis in above three groups at the day 30 and the day 60. In conclusion, the present results demonstrated that sesame oil and squalene have a synergistic amelioration effect on lowering blood lipid and promoting the recovery of erectile and sexual function on hyperlipemia-induced reproductive damage rats at day 30. However, further studies should be carried out to deeply elucidate the molecular mechanisms of Sesame oil and squalene in lowering blood lipids and improving sexual function in vivo.

Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis

AimsTo construct the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on our microarray chip data for providing new insights into the pathogenesis of autoimmune hepatitis.MethodsThe ceRNA pairs were obtained by calculating the co-expression relationships among the differentially expressed lncRNAs (DELs), differentially expressed microRNAs (DEMis), and differentially expressed mRNAs (DEMs) with Pearson correlation analysis and hypergeometric distribution. The data of the differentially expressed genes were obtained from our previous studies in the concanavalin A-induced AIH mouse model. The biological functions of the ceRNA network were revealed by carrying out the GO and KEGG enrichment analysis. The expression of some differentially expressed genes constructed in the ceRNA pair was validated, and the correlation to liver injury was analyzed.ResultsThe mRNAs constructed in the ceRNA network were most significantly annotated in the GO terms of “inflammatory response” and enriched in “Cytokine-cytokine receptor interaction” and “MAPK signaling pathway”. The differences in the expression of Gm38975, mmu-miR-125a-3p, and Map3k13 between the model group and control group were significant, and the expression of these genes at a transcriptional level was positively or negatively correlated to the activity of ALT and AST as well as the amount of MDA and NO.ConclusionOur work is the first in its kind to predict and illustrate the comprehensive lncRNA-miRNA-mRNA ceRNA network associated with the etiopathogenesis of AIH. This study indicates to lay the foundation for revealing the potential roles of ceRNAs in the occurrence of AIH and provide novel treatment targets for this disease.

Effect of Family Integrated Care on maternal stress in preterm infants in the Neonatal Intensive Care Unit: A bi‐center experience

To compare the effect of family integrated care (FICare) on maternal stress in preterm infants with traditional non-parent neonatal intensive care unit (NICU) care. We continuously enrolled mothers and their preterm infants from two NICUs between August 2014 and April 2017; while one NICU applied the FICare model (FICare group) and the other performed standard non-parent care model (control group). Maternal stress was evaluated by the Parental Stress Scale: NICU (PSS: NICU) on admission and right before the discharge. A generalized linear model to adjust for potential confounders. Subgroup analysis was also performed for comparisons between two groups. A total of 215 mothers with preterm infants were included in this study, among whom 118 (54.88%) were in FICare group and 97 (45.12%) were in control group. The mean PSS: NICU score was 117.36 ± 26.27 on admission with no difference between two groups. Before being discharged home, the PSS: NICU score of parents in both groups was significantly reduced, with the score of FICare group was significantly lower than that of control group. In all sub-domains of PSS: NICU score as sights and sounds, baby looks and behavior score, and parental role, the scores of FICare group were significantly lower than control group. There was a simultaneous decrease of maternal stress for NICU preterm infants. FICare further facilitates reducing the maternal stress. It shall be encouraged to apply FICare model in NICUs.

Metformin modulates the gut microbiome in a mice model of high-fat diet-induced glycolipid metabolism disorder

IntroductionMetformin (MET) can regulate glucose and lipid levels, and the gut microbiota may be involved in the control of metabolism. We hypothesized that MET alleviates glucolipid metabolism disorder by modulating...