To investigate the efficacy of the hypoxia-inducible factor-1α (HIF-1α) inhibitor PX-478 in improving radiation-induced apoptosis in cardiomyocytes and to elucidate its molecular mechanisms.

H9c2 cells were divided into blank group, model group, experimental-L group and experimental-H group. The experimental-L, -H groups were cultured with PX-478 at concentrations of 5 and 10 mol·L^-1, respectively, while the other groups were cultured in normal medium. After 24 h of culture, all groups except the blank group were irradiated with 6 Gy X-rays to establish a model of radiation-induced cardiac injury and were subsequently cultured for another 24 h. Cell viability was assessed using the cell counting kit-8 assay; relative protein expression levels were determined by Western blotting; and apoptosis was detected using Annexin V/PI flow cytometry.

The relative expression levels of HIF-1α protein in the blank group, model group, experimental-L group and experimental-H group were 0.89±0.01, 1.05±0.01, 0.64±0.02 and 0.52±0.02; the relative expression levels of aquaporin-1 (AQP1) protein were 0.79±0.02, 0.94±0.02, 0.74±0.01 and 0.59±0.01; AQP4 protein levels were 0.89±0.01, 1.03±0.01, 0.68±0.01 and 0.50±0.01; B-cell lymphoma-2 (Bcl-2) protein levels were 0.78±0.02, 0.58±0.02, 1.00±0.03 and 0.82±0.03; Bcl-2-associated X protein (Bax) levels were 0.66±0.01, 0.96±0.01, 0.77±0.01 and 0.27±0.03; Caspase-3 levels were 0.83±0.01, 1.10±0.01, 0.71±0.02 and 0.30±0.01; the apoptosis rates were (4.05±0.60)%, (17.82±0.63)%, (9.35±0.41)% and (9.07±0.57)%, respectively. The above indicators in the blank, experimental-L, experimental-H groups showed statistically significant differences compared to the model group (all P<0.05).

PX-478 can improve radiation-induced cardiomyocyte edema and reduce apoptosis by inhibiting the abnormal activation of the HIF-1α/AQPs axis in H9c2 cells after irradiation, thereby regulating fluid metabolism.

To investigate the antitumor activity and mechanism of a pyrazole [1,5-a]pyrimidine derivative (BPPA) on human tongue squamous cell carcinoma Cal33 cells.

Cal33 cells were divided into blank group (normal culture), experimental-L, -M, -H groups (1, 2.5 and 5 μmol·L^-1BPPA) and combined group [2.5 μmol·L^-1BPPA and 5 mmol·L^-1 N-acety-L-cysteine (NAC)]. Cell viability was determined by thiazole blue assay. Cell apoptosis was measured using flow cytometry, while apoptosis-related protein expression levels were determined by Western blot analysis. Changes in reactive oxygen species and mitochondrial membrane potential were evaluated using immunofluorescence assay.

The survival rates of Cal33 cells in blank, experimental-L,-M,-H and combined groups were (99.56±0.91)%, (58.31±2.31)%, (47.93±1.67)%, (29.35±4.11)% and (70.27±1.21)%, respectively; cell apoptotic rates were (8.07±1.01)%, (44.04±0.94)%, (49.85±1.75)%, (66.79±0.83)% and (24.33±1.04)%, respectively; the relative fluorescence intensities of reactive oxygen species (ROS) were 1.23±0.21, 3.37±0.35, 15.53±1.46, 20.28±1.24 and 5.59±0.52, respectively; the mitochondrial membrane potential red fluorescence/green fluorescence values were 4.69±0.11, 4.24±0.12, 0.86±0.16, 0.46±0.05 and 2.99±0.11, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001). Compared with experimental-M group, the above indexes in combined group were statistically significant (P<0.01, P<0.001). The relative levels of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-Associated X protein (Bax) in blank, experimental-L,-M,-H groups were 1.00±0.02, 1.94±0.03, 3.73±0.06 and 4.64±0.08, respectively; the relative levels of anti-apoptotic protein Bcl-2 were 1.00±0.02, 0.75±0.04, 0.62±0.02 and 0.46±0.03, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001).

BPPA exhibits anti-head and neck cancer activity by ROS mediating the decrease in mitochondrial membrane potential, thereby inducing apoptosis.

To investigate the effect of circRNA_0044556 on the resistance of triple-negative breast cancer (TNBC) to paclitaxel (PTX) and the mechanism of drug resistance.

PTX resistant TNBC cells (MDA-MB-231/PTX) were obtained by exposing the human TNBC cell (MDA-MB-231) to increasing concentrations of PTX. MDA-MB-231 and MDA-MB-231/PTX cells in logarithmic growth phase were treated with circRNA_0044556 short hairpin RNA (sh-circRNA_0044556) and negative control (sh-NC), respectively. The groups were finally divided into MDA-MB-231-NC, MDA-MB-231-circRNA_0044556, MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups. The expression level of circRNA_0044556 in cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR); methyl thiazolyl tetrazolium assay and colony formation assay were used to observe cell proliferation; flow cytometry was used to observe cell apoptosisand; Western blot was used to observe the expression of cell proliferation and apoptosis-related proteins.

The relative expression levels of circRNA_0044556 in MDA-MB-231/PTX, MDA-MB-231 and MCF-10A cells were 6.08±0.59, 3.36±0.11 and 1.00±0.02, respectively, and the differences were statistically significant (all P<0.001). Proliferation rates of MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were (100.00±0.84)% and (54.38±1.20)%; the apoptosis rates were (2.41±0.34)% and (21.65±0.29)%, respectively, and the differences were statistically significant (all P<0.001). The proliferation rates of MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups were (112.29±1.19)% and (61.33±1.24)%; the apoptosis rates were (2.08±0.07)% and (14.38±0.16)%, respectively, the differences were all statistically significant (all P<0.001). The relative protein expression level of Ki-67 in MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were 1.00±0.02 and 0.67±0.02; the relative protein expression of Bcl-2-associated X protein (Bax) were 1.00±0.02 and 1.46±0.03; and the differences were statistically significant (all P<0.05). The relative relative protein expression levels of Ki-67 in MDA-MB-231/PTX-NC group and MDA-MB-231/PTX-circRNA_0044556 group were 1.00±0.03 and 0.81±0.01, respectively; the relative expression levels of Bax protein were 1.00±0.02 and 1.55±0.02, respectively; the relative expression levels of Bcl-2 protein were 1.00±0.03 and 0.79±0.01, respectively. The above indexes in MDA-MB-231/PTX-NC group were significantly different from those in MDA-MB-231/PTX-circRNA_0044556 group (all P<0.05).

Knocking down the expression of circRNA_0044556 can inhibit the malignant progression and PTX resistance of TNBC cells.

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 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 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.

To explore effect and mechanism of microRNA 142a-3p (miR-142a-3p) on adriamycin-induced nephropathy (AN).

BALB/c mice were randomly divided into normal group and model group. The model group was injected with 10.5 mg·kg^-1 doxorubicin at a time through the tail vein, and the normal group was injected with equal volume 0.9% NaCl by the same method. After 28 days of feeding, both sides of the kidney tissues were taken for experiment. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-142a-3p in the renal tissues. The expression levels of autophagy related protein 16-like protein 1 (Atg16l1) and inflammatory NOD-like receptor heat protein domain associated protein 3 (NLRP3), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the renal tissues were detected by Western blotting. Human embryonic kidney 293T cells were divided into Atg16l1-WT+NC transfection group (transfected pmirGLO-Atg16l1-WT and NC mimics) and Atg16l1-WT+miRNA-142a-3p group (transfected pmirGLO-Atg16l1-WT and miR-142a-3p mimics). Dual luciferase assay was used to detect the targeted regulation of miR-142a-3p on Atg16l1.

The expression levels of miR-142a-3p in kidney tissues of normal group and model group were 1.20±0.27 and 2.02±0.14; the expression levels of Atg16l1 were 0.81±0.13 and 0.57±0.12, NLRP3 were 0.49±0.11 and 0.82±0.14; IL-1β were 0.55±0.11 and 0.84±0.08; IL-18 levels were 0.41±0.15 and 0.74±0.09, respectively, and the above indexes in the model group were significantly different from those in the normal group (all P<0.05). The relative luciferase activity in Atg16l1-WT+NC transfection group and Atg16l1-WT+miRNA-142a-3p transfection group were 1.26±0.07 and 0.92±0.10, respectively, with statistical significance (all P<0.05).

MiR-142a-3p down-regulates the expression of target protein Atg16l1 in renal tissue of adriamycin nephropathy mice, which activates NLRP3 pathway of inflammatory bodies and promotes the progressive development of adriamycin-induced nephropathy.

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 observe the effect of Tetrahydropalmatine on the epidermal growth factor receptor / phosphatidylinositol 3-kinase/protein kinase B (EGFR/PI3K/AKT) signaling pathway in endometriosis dysmenorrhoea SD rats.

The endometriosis dysmenorrhoea model was replicated by auto-transplantation in 60 female SD rats of SPF grade. After successful modelling, the rats were randomly divided into model group, control group and experimental -L, -M, -H groups according to body mass, with 12 rats in each group; and another 12 normal rats were taken as the blank group. The blank and model groups were given 10 mL·kg^-1 0.9% NaCl by gavage, and the control group was given 0.25 mg·kg^-1 progesterone suspension by gavage. The experimental-L, experimental-M, experimental-H groups were given 10, 20 and 40 mg·kg^-1 Tetrahydropalmatine suspension by gavage, respectively. Six groups of rats were administered once daily for 4 weeks. After the last administration, 2 U of oxytocin was given to induce contractions, and the rats were observed for torsional responses. The serum levels of tumor necrosis factor -α (TNF-α), epidermal growth factor (EGF), and EGFR were measured by enzyme-linked immunosorbent assay in each group of rats, and the expression levels of EGFR, PI3K and AKT proteins in ectopic endometrial tissues were detected by Western blotting.

The number of twists in the experimental -M, -H groups and control group, model group, blank group were 9.25±1.42, 8.33±1.88, 11.17±2.41, 28.67±2.15 and 0; the inhibition rates were 67.74%, 70.95%, 61.05%, 0 and 0; serum TNF-α levels were (281.96±13.06), (278.75±10.39), (282.12±14.47), (303.59±9.09) and (274.26±15.33) ng·L^-1; serum EGF levels were (313.82±13.23), (308.26±10.90), (311.39±19.52), (336.04±17.60) and (301.67±27.17) pg·mL^-1; serum EGFR levels were (315.71±7.56), (311.43±11.04), (313.75±7.26), (333.56±14.22) and (307.86±17.94) ng·L^-1; the relative expression levels of EGFR protein were 1.60±0.39, 1.26±0.30, 1.40±0.40, 2.08±0.41 and 1.00±0.22; the relative expression levels of PI3K protein were 1.60±0.42, 1.21±0.18, 1.27±0.24, 2.01±0.41 and 1.00±0.19; the relative expression levels of AKT protein were 1.27±0.18, 1.11±0.10, 1.27±0.16, 1.64±0.28 and 1.00±0.07, respectively. Statistically significant differences were found between the above indicators in the experimental -M, -H groups compared to the model group (P<0.01, P<0.05).

Tetrahydropalmatine may play a therapeutic role in endometriosis dysmenorrhoea by interfering with the EGFR/PI3K/AKT signaling pathway.