Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

Melanoma is a highly invasive and lethal skin malignant tumor derived from melanocytes. It has the characteristics of high early metastasis and high mortality. In recent years, with the in-depth study of the pathogenesis of melanoma, it has been found that epigenetic modification, especially DNA methylation, is considered to be a universal intrinsic feature of melanoma development and evolution. This article reviews the research progress of abnormal DNA methylation genes in melanoma in detail, and summarizes the biomarker effect of DNA methylation genes, suggesting that the detection of abnormal DNA methylation genes in melanoma patients is hopeful as an early screening index and diagnostic marker for melanoma patients.

Melanoma is a highly invasive and lethal skin malignant tumor derived from melanocytes. It has the characteristics of high early metastasis and high mortality. In recent years, with the in-depth study of the pathogenesis of melanoma, it has been found that epigenetic modification, especially DNA methylation, is considered to be a universal intrinsic feature of melanoma development and evolution. This article reviews the research progress of abnormal DNA methylation genes in melanoma in detail, and summarizes the biomarker effect of DNA methylation genes, suggesting that the detection of abnormal DNA methylation genes in melanoma patients is hopeful as an early screening index and diagnostic marker for melanoma patients.

Objective To design a pocket diary for cancer pain patients, to explore the effect on improving their knowledge about pain control, and make them actively participate in cancer pain control activities. Methods The study was performed in Sichuan Cancer Hospital, it was conducted on 299 cancer patients, who were randomly divided into the experimental group ( 156 cases ) and the control group (143 cases), undergoing moderate-to-severe cancer pain in six standardized pain control demonstration wards. Patients from the experimental group recorded their adverse reactions and general routine care, with a cancer pain pocket diary, and the patients in the control group only got the general routine care. A questionnaire was used to test their level of cancer pain knowledge and degree of satisfaction before discharge. Results There was no significant difference in the pain assessment and drug use between the two groups (P>0. 05). The scores of adverse reactions prevention, adverse reactions report and misunderstanding identification of the experimental group were (15. 84 ± 1. 70), (15. 84 ± 1. 70) and (18. 52 ± 1. 16), respectively, which were significantly higher than those in the control group (t =5. 25, 2. 38, 13. 53, respectively;P<0. 05). In the experimental group, 98 patients were quite satisfied, 55 patients were satisfied, 3 patients were not satisfied. There was a significant difference between the two groups (Z =8. 87,P <0. 05). Conclusions The cancer pain pocket diary could improve the cancer patients′ knowledge about pain control, and make them actively participate in cancer pain control activities.

O-Carboxymethylchitosan (O-CMC) in 1000 g batch was prepared from chitin as starting material and its chemical structure was confirmed by analysis of IR and NMR. O-CMC solution, sodium hyaluronate (HA) solution and physiological saline were used in Sprague-Dawley rat model for prevention of postsurgical adhesions; after 7 days of an abdominal operation, the 3 groups were evaluated according to Belluco standard, the mean scores of O-CMC group, HA group and physiological saline group were 2.5 +/- 3.1, 3.3 +/- 3.6 and 10.3 +/- 1.0, respectively. Histological inspection showed that in O-CMC group, mesothelial cells on peritonaeum or cecum surfaces were almost restored; in HA group the injured surface of peritonaeum was mostly repaired, but in physiological saline group the injured surface of cecum was just a little repaired; there were extensive adhesions between peritonaeum and cecum, and inflammatory response was quite serious. Experimental results indicated that O-CMC and HA had excellent efficiency and O-CMC was slightly better than HA for the prevention of postsurgical adhesions.
Abdomen ; surgery ; Animals ; Chitosan ; analogs & derivatives ; therapeutic use ; Female ; Intestinal Diseases ; prevention & control ; Male ; Postoperative Complications ; prevention & control ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Adhesions ; prevention & control

OBJECTIVE: To investigate the preventive and therapeutic effects and the possible mechanisms of Dilingdan Decoction (DLDD), a compound Chinese herbal medicine, on rats with renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHODS: Sixty SD rats were randomly divided into sham-operated group, untreated group, enalapril-treated group and DLDD-treated group. Blood urea nitrogen (BUN), serum creatinine (SCr), urine protein quantization in 24 hours and pathological changes of the obstructed kidney were observed. The expressions of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN) and laminin (LN) were detected by immunohistochemical method and colored-multimedia pathological image analysis system. RESULTS: Massive inflammatory infiltrates and collagen expression in renal interstitial in the untreated group were observed on the 7th day. Compared with the sham-operated group, percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions in the untreated group were markedly increased (P<0.05), while the percentage of area of interstitial fibrosis was decreased in the DLDD-treated group as compared with the untreated group (P<0.05). On the 14th day, the percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions were declined in two treated groups as compared with the untreated group (P<0.05), but had no statistical difference in biochemical indicators, including BUN, SCr and 24-hour urinary protein. On the 21st day, the level of SCr and the percentage of area of TGF-beta1 expression in the DLDD-treated group were lower than those of the enalapril-treated group (P<0.05). CONCLUSION: DLDD can reduce the excretion of urinary protein and the degree of interstitial fibrosis, and significantly inhibit the expressions of TGF-beta1, alpha-SMA, FN and LN. DLDD is superior to enalapril in protecting renal function after long-time application in rats.

The radical compliance of small diameter artificial vascular grafts was measured by a device made of laser micrometer, pressure transducer, A/D card, micro computer and pulsed circulation loop, the volumetric compliance was measured by a device made of micro-syringe and pressure transducer; the longitudinal compliance was calculated from volumetric compliance and radical compliance. The research results showed that the radical compliance, volumetric compliance and longitudinal compliance would rise not only with the increase in polyurethane (PU) elasticity and salt/polymer ratio (or porosity), but also with the decrease in dipping layers (or wall thickness). Circumferential moduli E zeta and longitudinal moduli E theta could be calculated from volumetric compliance and longitudinal compliance respectively; E theta and E zeta would decrease with the increase in PU elasticity and salt/polymer ratio, but was independent on number of dipping layers. Small diameter PU artificial vascular grafts with compliance close to natural vein or artery can be prepared by choosing of more elastic PU materials (Chro or PCU1500), optimization of salt/polymer ratio (6:1), and the number of dipping layers (4-6 layers).
Biocompatible Materials ; chemistry ; Blood Vessel Prosthesis ; Compliance ; Elasticity ; Humans ; Polyurethanes ; chemistry

OBJECTIVETo investigate the immune privilege induced by the Fas ligand (FasL) expressed by cotransplanted testicular Sertoli cells in islet allografts, and the effect of FasL gene transfection on islet cells in pancreatic islet allografts.

METHODSAllogeneic islets and testicular cells were cotransplanted into diabetic recipients. Pancreatic islets were infected with the recombinant adenovirus, AdV-FasL, and transplanted into diabetic recipients. Allograft survival, islet function, apoptosis of infiltrative lymphocytes in allografts and gene transfected islet allografts were analyzed.

RESULTSAll animals receiving islet allograft alone returned to a diabetic state in a few days (mean survival time 6.3 +/- 0.6 days). When the quantity of testicular cells cotransplanted with islets increased to 1 x 10(7), all animals remained normoglycemic throughout the follow-up period (60 days). FasL expression by cotransplanted Sertoli cells induced apoptosis of activated lymphocytes. Rejection of allografts in the FasL gene transfer group was accelerated and allograft survival was shortened to 3.4 +/- 0.2 days (P < 0.05). Pancreatic islets infected with AdV-FasL demonstrated positive staining for FasL at 24h after transplantation, with increased intensity at 48h. Apoptosis assays of pancreatic islet allografts at 24h and 48h revealed apoptosis of transfected islets.

CONCLUSIONSFasL-expressing testicular Sertoli cells can induce apoptosis of activated lymphocytes. Cotransplantation of testicular cells allows long-term survival of allogeneic islets because of immune privilege, but the direct expression of FasL on islet allografts infected with AdV-FasL accelerates islet rejection via islet apoptosis and granulocyte infiltration.

Animals ; Apoptosis ; Fas Ligand Protein ; Immunohistochemistry ; Islets of Langerhans Transplantation ; mortality ; Male ; Membrane Glycoproteins ; genetics ; physiology ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Transplantation, Homologous

Objective To evaluate J-pouch coloanal anastomosis after low anterior resection for the middle and low rectal carcinoma. Methods From January 1998 to July 2002, 120 patients undergoing low anterior radical resection for the middle or low rectal carcinomas were divided into groups of coloanal anastomosis and that of 5 cm colonic J-pouch-anal anastomosis. WT5”HZResults These two groups were well matched for gender, age and histologic stage. There were no significant differences in operative time, hospital stay, complications, postoperative recurrence rate and postoperative survival time between the two groups as founded by an average follow-up of 18 months. The mean distance from the inferior edge of the tumor to the dentate line was (3 6?1 5) cm in the J-pouch group, significantly less than that in coloanal anastomosis group of (5 2?1 9) cm, ( P =0 000). Defecation frequency, urgency and incontinence were significantly improved at 3 months and 12 months after operation in the J-pouch group ( P 0 05). Conclusion J-pouch coloanal anastomosis after low anterior resection for the middle and low rectal carcinoma significantly improves the short-term bowel function after operation.

Objective To investigate the correlation between clinicopathologic factors and peritoneal dissemination from gastric cancer, and the impact of palliative resection on the prognosis of patients with gastric cancer complicated by peritoneal dissemination. Methods Based on our database built in 1994, the clinicopathologic data and the result of follow-up of all gastric cancer patients were analyzed retrospectively using the software of SPSS. Results One hundred and five out of 792 (13. 3% ) patients with primary gastric cancer were found complicated with peritoneal dissemination. The clinicopathologic factors in patients with peritoneal dissemination were significantly correlated with primary tumor penetrating through serosa, lymph node metastasis, primary tumor involving whole stomach, undifferentiated carcinoma, Borrmann IV and female gender (P