Aim To investigate the effects of polyI:C on angiogenesis in mouse prostate carcinoma and its mechanisms.Methods Prostate carcinoma bearing mice were randomly divided into two groups according to tumor volume:contrl group and polyI:C group.After seven times′treatment,the mice were sacrificed.The content of NO in tumor was measured by nitric oxide assay kit.Tumor tissues were partly performed hematoxylin-eosin staining to observe morphological changes and distribution of vasa.Immunohisto chemical staining was used to observe the expression of VEGF,eNOS and AQP1.Results The content of NO in polyI:C group and the control was(1.22?0.77)?mol and(8.73?5.34)?mol respectively,and there was significant difference between two groups(P

Objective To investigate the effects of polyi:c on angiogenesis in mouse prostate carcinoma tissue and their possible mechanisms.Methods Mouse prostate carcinoma models were randomly divided into two groups according to tumor weight:control group and polyi:c group.After treatment for 7 times,the mice were sacrificed and the tumor tissues were cut for weighing,calculating the tumor inhibitory rate and tumor index.Hematoxylin-eosin staining and immunohistochemical staining were performed to observate the morphological changes of prostate carcinoma tissues,distribution of vasa and expressions of vascular endothelial growth factor (VEGF) and endothelial nitric-oxide synthase (eNOS).Results In polyi:c group,the mean tumor inhibitory rate was 67.85% and the tumor index was(5.42?0.17)%;in control group,the tumor index was(14.45?1.06)%; there was significant differences between polyi:c group and control group( P

Aldo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aldo-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form p-p interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound.

Objective To investigate the protective effect of berberine on acute hypoxia induced by sodium nitrite (NaNO2) in mice.MethodsThe animal model of acute hypoxia was established with NaNO2. Then the mice were treated with berberine by gavage in three different doses of 2.0 mg/kg, 4.0 mg/kg, and 8.0 mg/kg once everyday respectively for 6 days. The survival time according to the last breath, the breath time and open mouth times of animals were recorded. The superoxide dismutase (SOD), maleic dialdehyde (MDA), nitric oxide (NO) and lactic dehydrogenase (LDH) in brain tissue were tested. The pathological change was examined by HE staining.ResultsBerberine could significantly prolong the living time of acute hypoxia mice induced by NaNO2 and breath time after decapitation ( P<0.05, P<0.01), increase the activity of SOD and LDH, decrease the content of MDA and NO in brain tissue of hypoxia mice ( P<0.05, P<0.01). Under microscope, there were meningorrhagia, cellular necrosis in brain tissues of model animals, but no pathological changes found in berberine-treated animals.ConclusionBerberine has certain protective effect on acute hypoxia induced by NaNO2 in mice.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.