UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer

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.

The research progress on the correlation between metabolic syndrome and lumbar disc herniation / 中国医师杂志

Metabolic syndrome is a group of clinical syndromes characterized by overweight or obesity, hypertension, dyslipidemia, impaired glucose metabolism, and insulin resistance.It is a group of metabolic associated risk factors.Lumbar disc herniation (LDH) is one of the most common diseases nowadays, and its risk factors include obesity, diabetes, and abnormal blood lipid.In recent years, the relationship between LDH and metabolic syndrome (MetS) has been valued by scholars.Although some studies have suggested that MetS is related to LDH, the study of the correlation between MetS and LDH at home and abroad is relatively rare.To explore the possibility of using MetS for the prevention and control of LDH, this paper reviews the research progress of the relationship among MetS, the various components, and LDH.

3D printing technology in the surgical treatment of complex fracture application value / 中国医师杂志

With the progress of science technology,the 3D technology has raised comprehensive attention for its application value in medical field,especially in the orthopedic field.It has been mainly used before complicated orthopedic surgeries,and several studies have focused on 3D duplicated materials used in the treatment of bone defect.However,there are seldom studies about the 3 D technology used during surgeries,such as whether it is possible to 3D print internal fixation materials of bone fracture (the materials have biodegradability and excellent biomechanical characteristics),which can not only promote the healing of fracture,but also reduce the pain of second surgery for the patient.This paper reviews and summarizes the exploration of foreign and domestic scholars about the application value of 3 D printing technology used in complicated bone fracture,and proposes a forecast to the developing trend of the technology used in future orthopedic surgeries.

Activity of cathepsin D and alpha-1 antitrypsin in patients with hip or knee osteoarthritis / 中南大学学报(医学版)

Objective: To assess the activity of cathepsin D (CAT-D) and alpha-1 antitrypsin (AAT) in blood in patients with hip or knee osteoarthritis, and to explore whether these two enzymes could be served as serum biomarkers for cartilage degeneration. Methods: hTe activity of CAT-D and AAT in blood serum of 44 women and 26 men with hip or knee osteoarthritis was determined by the method of ELISA before total joint replacement and on the 10th day atfer the surgery. One hundred healthy volunteers were chosen as the control. All datawere analyzed by using SPSS19.0 sotfware. Results: Compared with the controls, the activity of CAT-D in patients with osteoarthritis was decreased by 25% (P0.05), but it was increased by 80% after the surgery than that in the control group (P0.05). hTe gender, hypertension, diabetes and age did not affect the activities of the 2 enzymes (P>0.05). Conclusion: AAT might be a possible inflammatory indicator in the osteoarthritis. CAT-D and AAT enzymes are not affected by gender, age, hypertension and diabetes, etc, and they might be served as potential biomarkers for cartilage degradation.

Homology Modeling for the Structure of the Soluble Segment of TRAIL / 中国肿瘤生物治疗杂志

Objective: In order to further investigate the structural/functional relationship of TRALL. Methods: We did homology modeling for the extracellular segment of TRAIL, which is from R117 to G281, totally 165 aa residues long. The modeling software is Insight II from MSI/Biosym and the modeling work is based on the three dimensional structure of TNF-?. Results: From the modeling result, it can be seen that the modeled structure of TRAIL contains 10 ?-sheets and homologs for all these sheets could be found in TNF-?. This just confirms with the principle that the structurally con-seived regions within molecules of the same structure family should experience relatively small sequence mutations. In addition, the credibility of the modeled structure is checked by the way of inverse folding from Profile-3D. Conclusion: The result shows modeled structure is generally correct.