To investigate the effect of venetoclax (Vene) on cell proliferation and apoptosis in acute myeloid leukemia (AML) by regulating the microRNA-410-3p (miR-410-3p)/high mobility group protein B1 (HMGB1) axis.

THP1 cells were randomly divided into control group (normal culture), experimental group (100 nmol·L^-1 Vene treatment), inh-NC group (experimental group + transfection of inh-miR-410-3p negative control), inh-miR-410-3p group (experimental group + transfection of inh-miR-410-3p), inh-NC combined with sh-NC group (inh-NC group + transfection of sh-HMGB1 negative control), inh-miR-410-3p combined with sh-NC group (inh-miR-410-3p group + transfection of sh-HMGB1 negative control), sh-HMGB1 group (inh-miR-410-3p group + transfection of sh-HMGB1). The relative expression levels of miR-410-3p and HMGB1 mRNA were detected by real-time quantitative polymerase chain reaction; immunofluorescence assay was used to detect the positive expression of HMGB1; 5-ethynyl-2′-deoxyuridine (EdU) was used to detect cell proliferation; Western blot was used to detect the relative expression levels of B lymphocytoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax).

The relative expression levels of miR-410-3p in the control group, experimental group, inh-NC group, inh-miR-410-3p group, inh-NC combined with sh-NC group, inh-miR-410-3p combined with sh-NC group and sh-HMGB1 group were 1.00±0.15, 3.76±0.31, 3.64±0.33, 1.69±0.20, 1.00±0.17, 0.42±0.06, 0.89±0.07, respectively; the relative expression levels of HMGB1 mRNA were 1.00±0.13, 0.62±0.07, 0.65±0.06, 0.93±0.11, 1.00±0.15, 1.93±0.21, 1.14±0.16, respectively. The relative fluorescence levels of HMGB1 in the control group, experimental group, inh-NC group and inh-miR-410-3p group were 1.00±0.16, 0.55±0.07, 0.58±0.08, 0.82±0.14, respectively. The cell proliferation rates of inh-NC combined with sh-NC group, inh-miR-410-3p combined with sh-NC group and sh-HMGB1 group were (11.46±1.95)%, (37.82±5.31)%, (16.14±3.05)%, respectively; the relative expression levels of Bcl-2 protein were 1.00±0.14, 4.17±0.39, 1.33±0.18, respectively; the relative expression levels of Bax protein were 1.00±0.16, 0.32±0.08, 0.91±0.13, respectively. The differences of above indexes were statistically significant between control group and the experimental group, between inh-NC group and the inh-miR-410-3p group, between inh-NC combined with sh-NC group and inh-miR-410-3p combined with sh-NC group, between inh-miR-410-3p combined with sh-NC group and the the sh-HMGB1 group (all P<0.001).

Vene can inhibit the proliferation of AML cells and induce apoptosis of AML cells by regulating the miR-410-3p/HMGB1 axis.

To observe the clinical efficacy and safety of escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets in the treatment of patients with Parkinson’s disease.

The patients with Parkinson’s disease were randomly divided into control group and treatment group. The control group received levodopa and benserazide hydrochloride tablets 125 mg per time, tid, orally. On the basis of control group, the treatment group received escitalopram oxalate tablets 10 mg per time, qd, orally. Two groups were treated for 3 months. The clinical efficacy, Montreal cognitive assessment (MoCA) scores, Hamilton depression rating scale (HAMD) scores, unified Parkinson’s disease rating scale (UPDRS) scores, the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and nerve growth factor (NGF), and safety were compared between two groups.

Treatment group was enrolled 116 cases, 4 cases dropped out, and 112 cases were finally included in the statistical analysis. Control group was enrolled 116 cases, 2 cases dropped out, and 114 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control group were 82.14% (92 cases / 112 cases) and 65.79% (75 cases / 114 cases), with significant difference (P<0.05). After treatment, the MoCA scores of treatment and control groups were (24.89±2.87) and (19.58±2.62) points, the HAMD scores were (10.45±1.06) and (15.84±1.49) points, the UPDRS scores were (40.06±5.28) and (47.78±5.52) points, the IL-6 levels were (4.12±0.63) and (6.71±1.13) mg·L^-1, the TNF-α levels were (8.71±1.64) and (11.14±2.05) mg·L^-1, the NGF levels were (41.56±5.20) and (30.47±4.14) ng·mL^-1, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of treatment group were somnolence and nausea/vomiting, while those in control group were nausea/vomiting and constipation. The total incidences of adverse drug reactions in treatment and control groups were 15.18% and 12.28%, without statistically significant difference (P>0.05).

Escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets significantly improves clinical efficacy in the treatment of patients with Parkinson’s disease, which can significantly ameliorate the inflammatory responses and neurotrophic factor levels, without increasing the incidence of adverse drug reactions.

To evaluate the pharmacokinetic characteristics and safety of delafloxacin, a new fluoroquinolone drug, in Chinese healthy subjects, and to evaluate the expected microbiological efficacy of delafloxacin in treating infections caused by Staphylococcus aureus and Streptococcus pneumoniae through pharmacokinetic/pharmacodynamic analysis.

This trial consists of two parts. The first part is a randomized, double-blind, placebo-controlled, single-dose/multiple-dose administration trial with a dose range of 150-450 mg. The second part is a randomized, open-label, double-period, self-crossover trial comparing the pharmacokinetic similarities between a 300 mg intravenous infusion of the test drug and the reference drug. Combined with the in vitro pharmacodynamic data of delafloxacin against Staphylococcus aureus and Streptococcus pneumoniae clinically isolated in China, the Monte Carlo simulation method was used to analyze the probability of target attainment and cumulative fraction of response of the 300 mg q12 h intravenous infusion over 60 min and to evaluate the expected microbiological efficacy.

After administering 150, 300 and 450 mg of delafloxacin to Chinese healthy subjects in single doses, the C_max, AUC_0-t and AUC_0-∞ increase proportionally with the dose. The apparent volume of distribution ranged from 45.79 to 144.38 L. The elimination half-life of each dose group ranged from 2.99 to 11.87 h. The cumulative urinary excretion rates of (47.69±8.11)% and (73.71±9.32)% were observed for single doses of 300 and 450 mg, respectively, suggesting that the primary route of excretion was renal. The 90% confidence interval of C_max, AUC_0-t and AUC_0-∞ of test drug over reference drug after single-dose intravenous infusion are all within 80.00%-125.00%. After reaching steady state with multiple-dose administration in the 300 mg group, the plasma exposure level was similar to that of the single-dose administration group.

Single-dose intravenous infusion of 150-450 mg delafloxacin in healthy subjects showed linear pharmacokinetic characteristics, and there was no accumulation after 300 mg q12 h administration. Adverse effects were mild, indicating good safety, and good microbiological efficacy.

To explore the therapeutic effects and mechanisms of Dunhuang Xiexin decoction on mice with ulcerative colitis (UC).

Mice were randomly divided into blank group (0.9% NaCl), model group (0.9% NaCl) and experimental-L, -M, -H groups (2.93, 5.85, 11.70 g·kg^-1 Dunhuang Xiexin decoction water extracts) with 10 cases per group for 7 days. Meanwhile, apart from the blank group, the other four groups of mice were allowed adlibitum access to drinking water containing 3% sodium dextran sulfate for 7 consecutive days to establish the UC model. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in mouse serum were determined by enzyme-linked immunosorbent assay. The expression levels of occludin, zonula occludens-1 (ZO-1) and phospho nuclear factor kappa B p65 (p-NF-κB p65) in colonic tissues was detected by Western blot.

The serum TNF-α levels in the experimental- M, - H groups, model group and blank group were (397.57±33.05), (389.41±22.57), (472.19±18.70) and (355.92±31.86) pg·mL^-1; the IL-1β levels were (73.06±18.38), (62.60±9.80), (98.94±27.50) and (55.26±18.14) ng·mL^-1; the IL-6 levels were (153.23±32.96), (148.12±23.53), (239.35±50.99) and (131.36±27.58) pg·mL^-1; the relative expressions levels of occludin protein in colon tissues were 0.80±0.13, 1.03±0.24, 0.57±0.15 and 1.10±0.03; the relative expressions levels of ZO-1 protein were 0.90±0.21, 1.09±0.10, 0.73±0.16 and 1.29±0.03; the relative expressions levels of p-NF-κB p65 protein were 0.75±0.12, 0.53±0.08, 1.15±0.19 and 0.43±0.21, respectively. There were significant differences between the experimental- H group and the model group (P<0.05).

Dunhuang Xiexin decoction may improve ulcerative colitis in mice by repairing the intestinal barrier and inhibiting the NF-κB signaling pathway to reduce the release of inflammatory factors.

To investigate the mechanism of action of harmine (HM) in anti-Echinococcus granulosus (E.g) based on non-targeted metabolomics.

The aseptically cultured fine-grained E.g was divided into blank group (KB group, conventional culture), solvent group (DMSO group, DMSO 2 μL) and administration group (HM group, 20 mmoL·L^-1 HM solution 2 μL). Survival rate was observed by eosin staining after 48 h of intervention and the ultrastructural changes were observed by scanning electron microscopy, respectively. Meanwhile, non-targeted metabolomics analysis was performed based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) technology on each group of E.g to screen the differential metabolites and explore the effect of harmine on the metabolic profile of E.g.

Eosin staining and scanning electron microscopy results showed that harmine had a significant inhibitory effect on E.g in vitro. Metabolomics results showed that there were a total of 15 metabolites with significant differences between the harmine and blank groups (all P<0.05). Enrichment of the differential metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that harmine mainly affected the metabolic pathways of amino acid metabolism, fatty acid metabolism and nucleotide metabolism in E.g.

Harmine had a significant inhibitory effect on E.g, the mechanism of which may be related to the regulation of amino acid metabolism, fatty acid metabolism and nucleotide metabolism pathways, which can provide a new way of thinking for the development of the subsequent anti-cystic echinococlosis drug targets.

To investigate the effect and mechanism of loganin on retinopathy in diabetic retinopathy (DR) rats.

DR rats were established by injection of streptozotocin and high glucose and high fat. They were randomly grouped into model group (0.9% NaCl), experimental -L group, experimental-H group (50, 100 mg·kg^-1 loganin), combined group [100 mg·kg^-1 loganin+10 mg·kg^-1 lysophosphatidic acid (LPA)] and 10 normal rats were taken as control group (0.9% NaCl). After the intervention, retinal histomorphology, the levels of inflammatory factors and oxidative stress, apoptosis of ganglion cells, and the expression of Ras homologous gene family member A (RhoA) and Rho associated coiled coil-forming kinase (ROCK) proteins in retinal tissue were measured in turn.

The number of retinal ganglion cells in experimental -L, -H groups, combined group, model group and control group were 19.75±1.90, 24.32±2.15, 17.80±1.94, 15.44±1.65 and 28.30±2.02; the levels of interleukin-6 were (85.67±8.61), (68.88±6.91), (98.52±9.88), (108.24±10.83) and (62.08±6.22) ng·L^-1; the levels of tumor necrosis factor -α were (150.24±15.11), (110.38±11.06), (186.94±18.77), (200.05±20.08) and (105.34±10.55) ng·L^-1; the levels of malondialdehyde were (7.52±0.78), (4.76±0.48), (9.52±0.96), (10.85±1.09) and (4.58±0.46) μmol·mg^-1; the superoxide dismutase activities were (62.05±6.21), (78.22±7.83), (52.11±5.23), (50.21±5.04) and (79.61±7.98) U·mg^-1; the apoptosis rates of ganglion cells were (12.71±1.06)%, (6.98±0.93)%, (14.69±1.30)%, (19.50±1.42)% and (2.15±0.38)%; the relative expression levels of RhoA protein were 0.81±0.09, 0.42±0.05, 1.08±0.11, 1.16±0.12 and 0.38±0.04; the relative expression levels of ROCK protein were 1.28±0.13, 0.77±0.08, 1.72±0.18, 1.85±0.19 and 0.63±0.07, respectively. Compared with the model group, the above indexes of the control group, experimental -H group and combination group had statistical significance (all P<0.05).

Loganin may improve retinopathy in DR rats by inhibiting the activation of RhoA/ROCK pathway, inhibiting inflammation and oxidative stress response.

Probing whether salivary acid-binding immunoglobulin-like agglutinin-15 (Siglec-15) promotes hepatocellular carcinoma proliferation and migration by regulating the signal transducer and activator of transcription 1/3 (STAT1/STAT3) pathway.

SMMC-7721 and BEL-7402 cells were divided into empty vector groups: S-NC and B-NC groups (NC siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively), Siglec-15 knockdown expression group: S-si-Siglec-15-3 and B-si-Siglec-15-3 groups (Siglec-15-3 siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively). The proliferation ability of the cells were detected by methyl thiazolyl tetrazolium (MTT); the longitudinal and lateral migration ability of the cells were detected by Transwell and scratch assay; the expression of STAT3, phosphorylation of STAT3 (p-STAT3), STAT1, phosphorylation of STAT1 (p-STAT1), Siglec-15 was detected by Western blot.

Cell viability values at 24 h in the S-NC group, S-si-Siglec-15-3 group, B-NC group and B-si-Siglec-15-3 group were 0.93±0.01, 0.87±0.03, 0.96±0.03 and 0.83±0.02, respectively; the vertical migration rates of cells were 100.00%, 36.40%, 100.00% and 52.20%, respectively; the healing rate of cell scratches at 24 h were (0.76±0.02)%, (0.53±0.02)%, (0.44±0.02)% and (0.36±0.03)%, respectively; STAT3 protein expression levels were 1.11±0.05, 0.66±0.05, 1.07±0.14 and 0.49±0.04, respectively; p-STAT3 protein expression levels were 1.07±0.04, 0.16±0.06, 0.78±0.05 and 0.32±0.03, respectively; STAT1 protein expression levels were 1.32±0.04, 0.71±0.04, 0.91±0.03 and 0.61±0.04, respectively; p-STAT1 protein expression levels were 0.99±0.04, 0.29±0.05, 0.67±0.04 and 0.20±0.06, respectively; Siglec-15 protein expression levels were 1.51±0.04, 0.93±0.05, 0.73±0.02 and 0.12±0.01, respectively. The differences between the S-si-Siglec-15-3 group and the S-NC group, between the B-si-Siglec-15-3 group and the B-NC group were statistically significant in all comparisons (P<0.05, P<0.01, P<0.001).

Siglec-15 promotes the proliferation and migration ability of hepatocellular carcinoma cells through the STAT1/STAT3 pathway.

To investigate the role of miRNA-633 in targeting the regulation of bone morphogenetic protein (BMP) and Smad protein pathways in promoting the proliferation and differentiation of dental pulp stem cells into dentin.

Human dental pulp stem cells were randomly divided into control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups. The ov-miRNA-633 and control groups were transfected with miRNA-633 overexpression vector and corresponding control blank vector, respectively. The anti-miRNA-633 and NC groups were transfected with miRNA-633 knockout vector and corresponding control blank vector, respectively. The cotransfection group was transfected with miRNA-633 overexpression vector + shRNA-N-Cadherin. Cell proliferation was detected by CCK-8 method. The expression levels of N-Cadherin were detected by real-time polymerase chain reaction. The expression levels of phosphorylated Smad 1/5/8 (p-Smad 1/5/8) were detected by Western blotting.

The optical density values on the 7^th day of the control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups were 1.65±0.05, 1.79±0.08, 1.55±0.05, 1.19±0.08 and 1.76±0.07; the relative expression levels of N-Cadherin mRNA were 1.09±0.03, 0.63±0.03, 1.06±0.04, 1.31±0.09 and 0.46±0.06; the relative expression levels of p-Smad 1/5/8 protein were 0.79±0.05, 1.28±0.08, 0.80±0.09, 0.62±0.06 and 1.09±0.18, respectively. The differences of above indexes were statistically significant between the ov miRNA-633 group and the control group (P<0.05, P<0.01). And the differences of above indexes were statistically significant between the cotransfection group and the anti miRNA-633 group (all P<0.05).

miRNA-633 could promote the proliferation and differentiation of dental pulp stem cells into dentin by inhibiting N-cadherin expression, activating the BMPs/Smad pathway.