To investigate the effects of microRNA-425-5p (miR-425-5p) targeting fibroblast growth factor 9 (FGF9) on the proliferation, glucose metabolism and olaparib resistance of ovarian cancer cells.

Human ovarian cancer cell line SKOV3 were divided into control group (normal culture), NC inhibitor group (transfected empty vector miR-NC), miR-425-5p inhibitor group (transfected miR-425-5p inhibitor), si-NC group (transfected si-NC on the basis of miR-425-5p inhibitor group), si-FGF9 group (transfected si-FGF9 on the basis of miR-425-5p inhibitor group). Quantitative real time polymerase chain reaction was used to detect the expression levels of miR-425-5p and FGF9 in cells. The cell proliferation rate was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay. Lactic acid production and glucose absorption were measured by lactic acid metabolism and glucose detection kit. The survival rate of cells in each group was detected by cell counting kit-8 assay. Western blot was used to detect signal transducer and activator of transcription 3/sirtuin 3 (STAT3/SITR3) signaling pathway related protein expression levels in each group.

The proliferation rate were (84.11±14.76)%, (36.12±6.95)%, (34.32±6.62)% and (77.37±12.83)% in the NC inhibitor group, miR-425-5p inhibitor group, si-NC group and si-FGF9 group, respectively; the relative lactic acid production were 1.02±0.13, 0.71±0.09, 0.74±0.09 and 0.89±0.10, respectively; the relative glucose absorption values were 0.99±0.14, 0.68±0.08, 0.70±0.09 and 0.91±0.11, respectively; the survival rates under 40 μmol·L^-1 olaparib were (59.86±9.55)%, (41.08±7.72)%, (40.25±7.02)% and (55.71±7.68)%, respectively; the relative expression levels of STAT3 protein were 1.01±0.17, 0.68±0.10, 0.66±0.09 and 0.88±0.12, respectively; the relative expression levels of SITR3 protein were 0.98±0.17, 1.84±0.28,1.85±0.29 and 1.23±0.20, respectively. The above indexes of miR-425-5p inhibitor group were compared with those of NC inhibitor group, and those of si-FGF9 group were compared with those of si-NC inhibitor group, and the differences were statistically significant (P<0.01, P<0.001).

Silting miR-425-5p can inhibit the proliferation and glucose metabolism of ovarian cancer cells, and reduce the resistance of cells to olaparib, which may be achieved by up-regulating FGF9 level and inhibiting STAT3/SIRT3 signaling pathway.

To investigate the effect of ulinastatin on epithelial-mesenchymal transition (EMT) of bladder cancer T24 cells.

Bladder cancer T24 cells were randomly divided into blank, control, experimental, combined groups. The cells in the blank group were cultured normally; and the cells in the control group were treated with RPMI-1640 medium containing 0.75 μmol·L^-1 KYA1797K; the cells in the experimental group were treated with RPMI-1640 medium containing 5.00 μmol·L^-1 ulinastatin and the cells in the combined group were treated with RPMI-1640 medium containing 5.00 μmol·L^-1 ulinastatin and 0.75 μmol·L^-1 KYA1797K. The treatment time was 48 hours. The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. Transwell assay was used to detect the invasion and migration ability of cells. The protein expression levels of epithelial-mesenchymal transition related proteins, wingless-type MMTV integration site family 3α (Wnt3α) and β-catenin were detected by Western blotting.

The survival rates of the blank group, control group, experimental group and combined group were (100.00±0.00)%, (73.28±6.37)%, (76.98±5.82)% and (40.36±3.21)%, respectively; the numbers of invasive cells were 66.83±8.18, 33.33±3.27, 38.67±4.32 and 11.33±1.21, respectively; the migration number were 79.33±6.38, 53.00±6.26, 52.33±3.14 and 28.33±5.28, respectively; the relative expression levels of E-cadherin protein were 0.23±0.08, 0.51±0.02, 0.58±0.05 and 0.82±0.03, respectively; the relative expression levels of Vimentin protein were 0.78±0.03, 0.55±0.02, 0.58±0.06 and 0.27±0.06, respectively; the relative expression levels of N-cadherin were 0.83±0.08, 0.59±0.02, 0.62±0.02 and 0.31±0.09, respectively; the relative expression levels of Wnt3α protein were 0.85±0.09, 0.28±0.13, 0.29±0.05 and 0.12±0.01, respectively; the relative expression levels of β-catenin were 0.81±0.05, 0.25±0.07, 0.22±0.03 and 0.08±0.02, respectively. The above indexes in the control group and experimental group were significantly different from those in the blank group and combined group (all P<0.05).

Ulinastatin can inhibit the epithelial-mesenchymal transition of bladder cancer T24 cells, and its mechanism may be related to the inhibition of Wnt signaling pathway.

To observe the intervention effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration (RAS-RH) on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway and radiation-induced heart disease (RIHD).

A model was constructed using a single whole-body X-ray irradiation at a dose of 8 Gy. SPF-grade male Wistar rats were randomly divided into the normal group, the model group (X-ray 8 Gy), the experimental-L group (X-ray 8 Gy+25 mg·kg^-1·d^-1 RAS-RH by gavage) and the experimental-H group (X-ray 8 Gy+50 mg·kg^-1·d^-1 RAS-RH by gavage), with ten rats in each group. 2 h after the last administration, cardiac function was evaluated using echocardiography; serum levels of inflammatory factors, including interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent; relative protein expression levels of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in myocardial tissue were detected using Western blotting.

The left ventricular ejection fraction (LVEF) in experimental-L group, experimental-H group, normal group and model group were (66.61±1.04)%, (71.89±0.69)%, (81.45±1.34)% and (47.62±1.67)%; the serum levels of IL-18 were (171.21±3.92), (145.60±3.37), (125.51±2.94) and (201.80±4.05) ng·mL^-1; the IL-1β levels were (43.03±0.68), (41.12±1.01), (36.12±0.98) and (51.19±0.85) ng·mL^-1; the TNF-α levels were (484.96±3.35), (441.24±3.94), (381.32±4.16) and (566.51±4.98) ng·mL^-1; the relative expression levels of NLRP3 protein in myocardial tissue were 0.54±0.02, 0.34±0.02, 0.20±0.02 and 0.75±0.03; the relative expression levels of Caspase-1 protein were 0.52±0.02, 0.44±0.02, 0.36±0.02 and 0.65±0.03; the relative expression levels of GSDMD-NT protein were 0.53±0.02, 0.42±0.01, 0.33±0.02 and 0.73±0.03; the relative expression levels of IL-18 protein were 0.50±0.02, 0.42±0.01, 0.13±0.01 and 0.63±0.02; the relative expression levels of IL-1β protein were 0.59±0.02, 0.42±0.02, 0.27±0.02 and 0.79±0.03, respectively. The indicators in the model group were significantly different compared to the normal group, and the indicators in the experimental-L and experimental-H groups were significantly different from the model group, with statistical significance (all P<0.05).

RAS-RH may improve RIHD by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.

To explore the underlying mechanism of TanshinoneⅡA (TanⅡA) exerted in myocardial infarction (MI) through nuclear factor E2-related factor 2 (NRF2)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/pyroptosis axis.

SD rats were randomly divided into sham operation group [only exposed the heart without left anterior descending (LAD) ligation], model group (LAD ligation) and experimental group (LAD ligation and 10 mg·kg^-1 TanⅡA). 2,3,5-Triphenyte-trazoliumchloride (TTC) staining was used to detect the area of infarction; Western blot was utilized to investigate the expression level of NRF2, NLRP3 and gasdermin D (GSDMD) in myocardial tissue. The H9c2 cells were divided into blank group (normal culture), model group [oxygen-glucose deprivation (OGD) culture], control group (normal culture and 40 μmol·L^-1 TanⅡA) and combined group (OGD culture and 40 μmol·L^-1 TanⅡA). Western blot was utilized to investigate the expression level of NRF2, GSDMD in cardiomyocyte. Creatine kinase MB (CK-MB) in cell culture supernatant were detected by automatic biochemical analyzer.

The proportion of myocardial infarction area in the sham operation group, model group and experimental group were 0, (58.64±13.41)% and (41.69±8.73)%, respectively; the relative expression of NLRP3 protein were 1.01±0.10, 2.12±0.26 and 1.48±0.11, respectively; the relative expression of GSDMD protein were 1.03±0.17, 2.22±0.20 and 1.40±0.17, respectively; the relative expression of NRF2 protein were 1.12±0.29, 0.51±0.02 and 0.96±0.10, respectively; the indicators of the model group compared with the sham operation group, and the indicators of the experimental group were compared with the model group, the differences were statistically significant (all P<0.05). The CK-MB in blank group, model group, control group and combined group were (54.30±19.24), (208.60±38.19), (46.76±13.63) and (126.10±42.87) U·L^-1, respectively; the relative expression of NRF2 protein were 1.37±0.14, 0.44±0.08, 1.34±0.17 and 0.79±0.11, respectively; the relative expression of GSDMD protein were 0.95±0.26, 1.97±0.17, 1.04±0.20 and 1.16±0.16, respectively. The indicators of the model group compared with the blank group, and the indicators of the combined group were compared with the model group, the differences were statistically significant (all P<0.05).

TanⅡA can alleviate myocardial infarction-induced myocardial injury through regulation NRF2/NLRP3/pyroptosis axis.

To investigate the effects and mechanism of Polygonum orientale flower (POR) extract on exercise arrhythmia (EA) in rats after exhaustive exercise.

The EA rat model was induced by 8 weeks of exhaustive weight-bearing swimming exercise and was randomly divided into model group and experimental -L, -M, -H groups, with 12 rats per group. Twelve normal rats were selected as the normal group. On the modeling day, normal and model groups were given pure water by intragastric administration. Experimental -L, -M, -H groups were given 50, 100 and 200 mg·kg^-1 POR extract solution by intragastric administration, respectively. Five groups were administrated with once a day for 8 weeks. The latent time and duration of arrhythmia in rats were detected by electrocardiograph. The contents of adenosine triphosphate (ATP), the activities of Na⁺/K⁺ATP and the contents of superoxide dismutase (SOD) in myocardial tissue were measured by corresponding kit. The transcriptional levels of calmodulin (CaM) and calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) in rat myocardium were measured by real-time fluorescence quantitative polymerase chain reaction.

The latent time of arrhythmia in experimental -M, -H groups and model group were (9.77±1.48), (10.61±1.61) and (7.44±2.12) min; the duration were (33.25±6.39), (20.01±3.89) and (71.44±13.68) min. The ATP contents in experimental -M, -H groups, model group and normal group were (26.45±2.96), (29.44±1.89), (10.38±1.22) and (34.50±4.24) ng·g prot^-1; the Na⁺/K⁺ ATP activities were (17.27±0.92), (19.57±1.33), (5.14±0.80) and (20.00±2.11) U·g prot^-1; SOD contents were (89.22±9.07), (86.29±7.22), (73.62±7.36) and (89.43±8.85) U·mg prot^-1; the relative expression levels of CaM mRNA in myocardial tissue were 1.28±0.08, 1.06±0.08, 2.34±0.30 and 1.00±0.10; the relative expression levels of CaMK Ⅱ mRNA in myocardial tissue were 1.46±0.09, 1.15±0.09, 2.80±0.19 and 1.00±0.11, respectively. Compared with model group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).

POR extract can effectively treat the rats with EA, and the mechanism is related to the increase of ATP contents, Na⁺/K⁺ ATP and antioxidant activities, and inhibition of Ca²⁺/CaM/CaMK Ⅱ signaling pathway.

To investigate the protective effects of monosialotetrahexosylganglioside (GM1) on hypoxic-ischemic brain damage (HIBD) in neonatal rats based on the ubiquitin C-terminal hydrolase L1 (UCH-L1)/brain-derived neurotrophic factor (BDNF) signaling pathway.

Twenty-day-old SD rats were randomly divided into model group, sham group and experimental group, with 10 rats in each group. Rats in model group and experimental group were lapped with left common carotid artery and placed in anoxic chamber with a certain oxygen to nitrogen ratio (8∶92) for 2 h to construct HIBD model. After the successful construction of the model, the experimental group was intraperitoneally injected with 20 mg·kg^-1·d^-1GM1, and the model group and sham group were injected with 0.9 % NaCl (0.25 mL·kg^-1). The modified neurological severity score (mNSS) was used to evaluate the degree of neurological damage in the treated rats. Cerebral infarction was detected by 2,3,5-triphenyte-trazoliumchloride staining method; cerebral water content was determined by wet and dry weight method; cognitive ability was assessed by Morris water maze test; apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; inflammatory factors were detected by enzyme-linked immunosorbent assay; UCH-L1 and BDNF protein levels were detected by Western blot.

After different treatments, the mNSS scores of sham group, model group and experimental group were (0.10±0.02), (2.60±0.45) and (1.50±0.20) points; the cerebral infarction rates were (0.89±0.11)%, (32.56±4.12)% and (18.56±2.52)%; the cerebral water content were (68.25±7.05)%, (88.87±9.26)% and (71.11±8.11)%; the latent period were (22.60±2.86), (38.60±4.11) and (25.50±3.33) s; the platform residence time were (125.50±17.68), (80.60±9.68) and (115.80±13.89) s; the platform crossing times were (2.80±0.35), (0.70±0.09) and (1.80±0.30) times; the apoptosis rates were (6.65±0.74)%, (21.88±3.05)% and (13.62±2.62)%; the tumor necrosis factor-α levels were (30.05±3.85), (121.61±18.85) and (82.14±11.65) pg·mL^-1; the levels of interleukin-1 beta were (92.55±12.15), (321.25±41.24) and (212.32±25.61) pg·mL^-1; interleukin-6 levels were (184.32±20.54), (275.62±31.12) and (208.65±22.65) pg·mL^-1; UCH-L1 protein levels were 1.00±0.22, 1.75±0.34 and 1.40±0.28; BDNF protein levels were 1.00±0.21, 1.68±0.38 and 2.54±0.41. There were statistically significant differences between sham group and model group (P<0.01, P<0.001). There were statistically significant differences between model group and experimental group (P<0.05, P<0.001).

GM1 can improve nerve cell apoptosis and inflammatory response by activating UCH-L1/BDNF signaling pathway, and play a protective role in neonatal rat HIBD.

To investigate the protective effect of Danzhi Jiangtang capsule on kidney of db/db mice with diabetic kidney disease (DKD) and its effects on the autophagy-lysosomal pathway.

The db/db mice were randomly divided into model group (0.2 mL·d^-1 0.9% NaCl), positive control group (45 mg·kg^-1·d^-1 irbesartan) and experimental-H, -M, -L groups (1 800, 900 and 450 mg·kg^-1·d^-1 Danzhi Jiangtang capsule), and another db/m mice were taken as blank group (0.2 mL·d^-1 0.9% NaCl), which were continuously infused for 8 weeks. The expression levels of sequestosome1 (P62), microtubule-associated protein light chain 3 (LC3), transcription factor EB (TFEB), lysosomal associated membrane protein 1 (LAMP-1) and cathepsin D (CTSD) were detected in renal tissues by Western blot.

The relative expression levels of P62 protein in blank group, model group, positive control group and experimental-H,-M,-L groups were 1.00±0.04, 7.66±0.27, 3.52±0.11, 2.21±0.09, 2.86±0.10 and 4.05±0.16; the LC3Ⅱ/Ⅰ levels were 1.00±0.02, 0.17±0.01, 0.71±0.08, 0.86±0.05, 0.80±0.04 and 0.73±0.06; the TFEB protein levels were 1.00±0.01, 0.17±0.01, 0.30±0.01, 0.63±0.01, 0.45±0.01 and 0.42±0.01; the LAMP-1 protein levels were 1.00±0.01, 0.28±0.02, 0.42±0.01, 0.77±0.00, 0.55±0.03 and 0.40±0.02; the CTSD protein levels were 1.00±0.04, 0.27±0.03, 0.47±0.04, 0.73±0.02, 0.63±0.01 and 0.52±0.02. The differences between the above indexes in the experimental-H, -M, -L groups and the model group were statistically significant (all P<0.01).

Danzhi Jiangtang capsule can improved renal damage in db/db mice, which may be related to the repair of autophagy-lysosome pathway, accelerate clearance of abnormal proteins and degradation of organelles.

To investigate the protective effect of hedysarum polybotrys polysacchcaide (HPS) on intestinal mucosal barrier in rats with splenic deficiency type diabetic gastroparesis.

The rat model of spleen deficiency DGP was prepared by multifactorial combined with low-dose intraperitoneal injection of Stretocin. The rats were randomly divided into blank group (pure water gavage), model group (pure water gavage), positive control group (0.09 g·kg^-1 metformin hydrochloride sustained-release tablet) and experimental-H,-M,-L groups (0.20, 0.10, 0.05 g·kg^-1 HPS), each group was administered by gavage once a day for 8 W. Measured blood glucose, diamine oxidase (DAO), lipopolysaccharides (LPS), D-lactate contents (D-LA) in serum by enzyme linked immunosorbent assay method; Claudin-1, Occludin, Zonula Occluden-1 (ZO-1) mRNA and protein expressions in lleal tissue were detected by reverse transcription-polymerase chain reaction and Western blot.

The blood glucose in the blank group, model group, positive control group, experimental-H,-M,-L groups were (5.04±0.40), (30.71±1.21), (18.63±6.72) and (19.90±3.30)mmol·L^-1; the DAO were (49.56±6.13), (192.19±24.40), (130.63±19.90) and (120.24±17.53) pg·mL^-1; the LPS were (41.11±4.56), (99.67±6.63), (64.51±8.59) and (63.07±4.89) ng·L^-1; the D-LA were (506.45±52.22), (1 826.49±224.17), (1 166.47±121.78) and (1 344.82±130.65) μg·L^-1; the relative expression levels of Claudin-1 mRNA were 1.03±0.32, 0.25±0.12, 0.94±0.40 and 0.71±0.21; the relative expression levels of Occludin mRNA were 1.07±0.48, 0.26±0.06, 1.23±0.42 and 0.99±0.47; the relative expression levels of ZO-1 mRNA were 1.00±0.13, 0.43±0.18, 0.85±0.07 and 0.69±0.08; the relative expression levels of Claudin-1 protein were 1.00±0.00, 0.21±0.19, 0.56±0.31 and 0.87±0.31; the relative expression levels of Occludin protein were 1.01±0.27, 0.38±0.11, 0.88±0.10 and 0.85±0.18; the relative expression levels of ZO-1 protein were 1.00±0.14, 0.43±0.04, 0.77±0.02 and 0.67±0.16. Compared with the the blank group, the above indexes in the model group had statistical significance (P<0.01, P<0.05); compared with the model group, the above indexes in the experimental-H had statistical significance (P<0.01, P<0.05).

HPS can reduce intestinal mucosal injury and maintain the integrity of the intestinal mucosal barrier in spleen deficiency DGP rats.

To investigate the intervention effect and mechanism of β-ecdyssterone on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) based on the regulation of autophagy by the adenosine 5′-monophosphate kinase-activated protein (AMPK)/mammalian target of rapamycin (mTOR).

BMSCs cells were divided into control group (normal culture), low-, middle- and high-dose groups (intervened with 0.01, 0.10 and 1.00 μmol·L^-1 ecdysterone). The expression of cell genes was determined by real-time quantitative polymerase chain reaction (qRT-PCR); and the relative expression level of cell proteins was determined by immunofluorescence (IF).

The relative expression levels of alkaline phosphatase (ALP) mRNA in the control group, low-, middle and high-dose groups were 1.01±0.14, 1.22±0.05, 1.28±0.05, 1.59±0.20; the relative protein expression levels of Runt-related transcription factor 2 (RUNX2) mRNA were 1.00±0.07, 1.45±0.07, 2.11±0.32, 4.67±1.45; the relative protein expression levels of phosphorylated AMPK protein were 0.07±0.01, 0.11±0.01, 0.06±0.01, 0.18±0.01; and the relative protein expression levels of Sequestosome 1 (p62/SQSTM1) protein were 1.72±0.02、1.67±0.02、0.94±0.01、0.04±0.01; the relative protein expression levels of p-mTOR protein were 0.66±0.01, 0.40±0.01, 0.42±0.01, 0.04±0.01; and the relative protein expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) protein were 0.07±0.01, 0.20±0.01, 0.87±0.05, 1.27±0.04, respectively. There were statistically significant differences between the low-, middle-, and high-dose groups and the control group (P<0.05, P<0.001).

β-ecdyssterone can regulate autophagy and promote osteogenic differentiation of BMSCs by activating the AMPK/mTOR pathway.

To evaluate the bioequivalence of domestic duloxetine hydrochloride enteric-coated tablets and original enteric-coated capsules in Chinese healthy subjects.

In a random, open, two periods, two sequence, self-crossover study, 40 cases healthy subjects in fasting test and 48 cases healthy subjects in fed test were given single oral test preparation and reference preparation 20 mg of duloxetine hydrochloride. The concentrations of duloxetine hydrochloride in plasma were determined by high performance liquid chromatography tandem mass spectrometry. The pharmacokinetic parameters were calculated using Phonenix WinNolin 8.0 software, and the bioequivalence of the test and the reference duloxetine hydrochloride was evaluated.

The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fasting test were as follows: C_max were (16.70±5.94) and (16.70±7.10) ng·mL^-1; AUC_0-t were (217.28±98.82) and (222.42±117.98) ng·h·mL^-1; AUC_0-∞ were (225.91±100.35) and (229.40±119.34) ng·h·mL^-1. The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fed test were as follows: C_max were (20.10±9.56) and (21.30±10.90) ng·mL^-1; AUC_0-t were (266.99±146.66) and (273.22±168.09) ng·h·mL^-1; AUC_0-∞ were (277.83±154.73) and (283.51±174.63) ng·h·mL^-1. The 90% confidence intervals of the main pharmacokinetic parameters of the test and reference preparations in fasting and fed tests were between 80.00%-125.00%.

The test and the reference duloxetine hydrochloride were bioequivalent under fasting and fed conditions.