Effect of 23­hydroxybetulinic acid on lung adenocarcinoma and its mechanism of action.

The present study aimed to investigate the effect and mechanism of Pulsatilla compounds on lung adenocarcinoma. The representative drug chosen was the compound 23-HBA. GeneCards, Swiss target prediction, DisGeNET and TCMSP were used to screen out related genes, and MTT and flow cytometry assays were used to verify the inhibitory effect of Pulsatilla compounds on the proliferation of lung adenocarcinoma cells. Subsequently, the optimal target, peroxisome proliferator-activated receptor (PPAR)-γ, was selected using bioinformatics analysis, and its properties of low expression in lung adenocarcinoma cells and its role as a tumor suppressor gene were verified by western blot assay. The pathways related to immunity and inflammation, vascular function, cell proliferation, differentiation, development and apoptosis with the highest degree of enrichment and the mechanisms were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Finally, the clinical prognosis in terms of the survival rate of patients in whom the drug is acting on the target was analyzed using the GEPIA database. The results indicated that Pulsatilla compounds can inhibit the proliferation of lung adenocarcinoma cells by blocking the cell cycle at the G1 phase. Subsequently, the related PPAR-γ gene was verified as a tumor suppressor gene. Further analysis demonstrated that this finding was related to the PPAR signaling pathway and mitochondrial reactive oxygen species (ROS) production. Finally, the clinical prognosis was found to be improved, as the survival rate of patients was increased. In conclusion, Pulsatilla compounds were indicated to inhibit the viability and proliferation of lung adenocarcinoma H1299 cells, and the mechanism of action was related to PPAR-γ, the PPAR signaling pathway and mitochondrial ROS. The present study provides novel insight to further explore the treatment of lung adenocarcinoma.

Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism.

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors. Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein-protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375. Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation. Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.

[Endoplasmic reticulum stress promotes the apoptosis of testicular germ cells in hyperlipidemic rats].

OBJECTIVE: To investigate the role of endoplasmic reticulum stress in the apoptosis of testicular germ cells in hyperlipidemic rats. METHODS: We randomly assigned 42 four-week-old male Wistar rats into a normal control group (n = 12) and a high-fat group (n = 30) to be fed on a normal diet and a high-fat diet, respectively, for 10 weeks. Then we measured the concentrations of triglyceride (TG) and total cholesterol (TC) in the serum using an automatic biochemistry analyzer, detected the apoptosis of testicular germ cells by TUNEL staining, and determined the protein and mRNA expressions of GRP78 and. caspase-12 in the testis tissue by immunohistochemistry and RT-PCR, respectively. RESULTS: The concentrations of TG and TC were significantly increased in the animals of the high-fat group ([3.00 ± 0.92] and [3.04 ± 0.39] mmol/L) as compared with the control rats ([1.43 ± 0.41] and [1.55 ± 0.23] mmol/L) (P < 0.01), and so was the apoptosis index of the testicular germ cells ([37.17 ± 2.74]% vs [5.16 ± 0.81]%, P < 0.01). The high-fat group, in comparison with the control, also showed remarkably upregulated protein and mRNA expressions of GRP78 (0.32 ± 0.03 and 0.86 ± 0.05 vs 0.19 ± 0.01 and 0.37 ± 0.03, P < 0.01) and caspase-12 (0.34 ± 0.02 and 0.87 ± 0.01 vs 0.12 ± 0.01 and 0.34 ± 0.03, P < 0.01) in the testis tissue. CONCLUSION: The apoptosis of testicular germ cells is increased in hyperlipidemic rats, which may be attributed to endoplasmic reticulum stress.

[Diet-induced obesity increases the apoptosis of testicular spermatogenic cells in pubertal male rats].

OBJECTIVE: To investigate the effect of diet-induced obesity on the apoptosis of testicular spermatogenic cells in pubertal male rats. METHODS: Forty healthy male rats were equally and randomly divided into a control and a high-fat group, the former fed on normal diet, while the latter high-fat and high-calorie diet. The testes of the rats were harvested at the end of 10 weeks for detection of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in the peripheral blood with the automatic biochemical analyzer. Pathological changes of the testis were observed under the light microscope, the apoptosis of the testicular cells detected by TUNEL, the expressions of Bcl-2 and Bax proteins determined by immunohistochemistry, and those of Bcl-2 mRNA and Bax mRNA measured by RT-PCR. RESULTS: The levels of TC, TG, LDL-C and HDL-C were significantly higher in the high-fat group (5.17 +/- 0.17, 1.18 +/- 0.09, 1.76 +/- 0.11 and 5.08 +/- 0.18) than in the control (1.38 +/- 0.12, 0.39 +/- 0.05, 0.97 +/- 0.07 and 0.75 +/- 0.06) (P < 0.05), so was the apoptotic index of spermatogenic cells (37.17 +/- 2.74 versus 5.16 +/- 0.81, P < 0.01), and the apoptotic spermatogenic cells were mainly spermatogonia and spermatocytes. The expressions of Bax protein and Bax mRNA were markedly higher in the high-fat group (153.26 +/- 8.74 and 1.08 +/- 0.12) than in the control (101.81 +/- 6.14 and 0.37 +/- 0.04) (P < 0.01), while those of Bcl-2 protein and Bcl-2 mRNA remarkably lower in the former (139.26 +/- 7.21 and 0.46 +/- 0.05) than in the latter (159.37 +/- 8.96 and 1.05 +/- 0.11) (P < 0.01). CONCLUSION: Diet-induced obesity can increase the apoptosis of spermatogenic cells in the rat testis, which may be associated with the reduced expression of Bcl-2 and elevated expression of Bax.

Efficacy and safety of tamsulosin for the treatment of benign prostatic hyperplasia: a meta analysis.

BACKGROUND: Pharmacological therapy has been considered as the first-line treatment for patients with uncomplicated benign prostatic hyperplasia (BPH). The aim of this study was to evaluate the efficacy and safety of tamsulosin compared with a placebo for treating BPH. METHODS: The randomized placebo-controlled trials (RCT) of tamsulosin for the treatment of BPH from all over the world were searched. PubMed, Ovid, ScienceDirect, EBSCO, CBM, and CNKI were searched, as well as a manual search of four Chinese journals: Chinese Journal of Andrology, National Journal of Andrology, Chinese Journal of Urology, and Journal of Clinical Urology was also performed. Two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies, with confirmation by cross-checking. Divergences of opinions were settled by discussion. Meta-analysis was processed by Rev Man 5.0 software, fail-safe number was performed by SAS8.0 software. RESULTS: Seven RCTs involving 2455 men met the inclusion criteria. The basic characteristics of patients were comparable in all the studies. Comparing three common criteria: international prostate symptom score (IPSS)/Boyarsky symptom score, maximum flow rate (MFR), quality of life (QOL), tamsulosin was better than placebo at improving IPSS and MFR, with no significant difference in the QOL. Adverse events of tamsulosin also showed no significant difference from the placebo group (Z=1.62, P=0.10, OR=1.22, 95% CI 0.96-1.54). CONCLUSIONS: Tamsulosin is better than placebo at improving IPSS and MFR. Adverse events of tamsuloisn show no significant difference compared with placebo. More high quality trials with larger samples and longer follow-up are proposed.