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As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.
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BACKGROUND: The surgical resection rate of pdmary hepatic carcinoma is low, thus, the local treatment arose more attention. Microwave coagulation therapy can inactivate rather than kill the hepatic carcinoma ceils. Slow-release chemotherapy has been used in treating primary hepatic carcinoma because it can form local high concentrations and last for a long time. OBJECTIVE: To observe the therapeutic effect of epirubicin-loaded chitosan microspheres combined with microwave coagulation on treating hepatocellular carcinoma in mica. METHODS: Epirubicin-loaded chitosan microspheres were prepared by using emulsion-chemical cross linking technique. The surface morphology and particles size of chitosan microspheres were observed by scanning electron microscope. Ultraviolet speotrophotometer was used to analyze the entrapment efficiency, entrapment efficiency and cumulative release rates of epirubicin-loaded chitosan microspheres. Totally 24 mice with transplanted subcutaneous H22 HCC were divided into 4 groups, which were respectively treated by microwave coagulation therapy, intratumoral injected with physiological saline after microwave coagulation therapy, intratumoral injected with epirubicin after microwave coagulation therapy, intratumoral injected with epirubicin-ioaded chitosan microspheres after microwave coagulation therapy. The tumor inhibitory rate was calculated. RESULTS AND CONCLUSION: The average diameter of chitosan microsphere was 105 μm, with uniformed particle diameter. The ratio of drug loading was 11% and the entrapment was 80%. The in vitro drug cumulative release rate was 84% after 2 weeks. The tumor inhibitory rates of the microwave coagulation combined with physiological saline, epirubicin, and drug carried microspheres groups were 8%, 20%, and 47%. It suggested that chitosan microsphere is a safe and effective slow-release dosage form, which exhibits strong anti-tumor effect when combined with microwave treatment.
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Objective:To evaluate the potential mutagenicity of Echinacea Herb P.E via salmonella typhimurium Ames test. Methods:To test the Echinacea Herb P.E diffusion through Ames test. In the plate incorporation test of Salmonella Typhimurium,the average number of spontaneous revertants of TA97,TA98,TAl00,and TA102 at four concentrations was calculated after incubation at 37 ℃ for 48 hours. Results:Whether added S 9 or not,the number of induced revertants when compared to that of spontaneous revertants did not increase statistically significant. The result of Ames test was negative. Conclusion:Echinacea Herb P.E will not cause the increase of the back mutation in murine typhoid salmonella which shows that Echinacea Herb P.E will not cause gene mutation.
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AIM: To explore the immunotheraptical drugs for multi-drug resistant pulmonary tuberculosis (MDR-TB). METHODS: 79 patients with MDR-TB were randomly assigned to two groups. 46 cases in M.vaccae group were treated with "3AkPaThLevL/15PaThLevL" and M. vaccae, and 33 cases in control group were treated only with "3AkPaThLevL/15PaThLevL". The clinical effect and T-lymphocyte subsets in patients were observed after being treated for 1,2 and 3 months, respectively. RESULTS: The sputum negative rates ((41.3)%, (63.0)%, and (80.4)%) and the X-ray resolution rates ((30.4)%, (50.0)%, and (67.4)%) of the M.vaccae group were superior to those ((12.1)%, (27.3)%, and (39.4)%, P
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0.05). Conclusion The improved puncture drainage of lateral ventricle for treating tuberculous meningitis was better than the traditional one, and was worthy of popularization.
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OBJECTIVE:To observe the hepatoprotective effect of compound glycyrrhizin in treating patients with multidrug resistant pulmonary tuberculosis(MDR-TB).METHODS:A total of 68 MDR-TB cases were enrolled:36(treatment group) were randomly assigned to receive additional glycyrrhizin,and 32(control group) to receive additional glucurolactone and legalon,the hepatoprotective effects and side effects between 2 groups were compared before and after treatment.RESULTS:The total effective rates of the treatment group and the control group were 94.4% and 62.5%,respectively 1month after hepatoprotective treatment,and significant difference was noted between 2 groups(P0.05).CONCLUSION:Compound glycyrrhizin has a reliable hepatoprotective efficacy and few adverse drug reactions in treating MDR-TB patients complicating with lesion of liver function.