Biomedical subjects

Xiang Wang

Publications and source records attributed to Xiang Wang.

100 records · Page 6Linked to original sources

PubMed2002

Ku affects the ataxia and Rad 3-related/CHK1-dependent S phase checkpoint response after camptothecin treatment.

Camptothecin (CPT) that targets DNA topoisomerase I is one of the most promising broad-spectrum anticancer drugs in development today. The cytotoxicity of CPT is S phase (S)-specific because the collision of advancing replication forks with CPT-topoisomerase I-DNA complexes results in DNA damage. After DNA damage, proliferating cells could actively slow down the DNA replication through an S checkpoint to provide time for repair. We report now that there is an activated S checkpoint response in CPT-treated mammalian cells. This response is regulated by Ataxia and Rad3-related (ATR)/CHK1 pathway. Compared with their wild-type counterparts, CPT-treated Ku80-/- cells showed stronger inhibition of DNA replication. This stronger inhibition had no relationship with DNA-dependent protein kinase (DNA-PK) activity but correlated with the higher activities of ATR and the higher activities of CHK1 in such cells. Not only caffeine, the nonspecific inhibitor of ATR, or UCN-01, the nonspecific inhibitor of CHK1, but also the specific CHK1 antisense oligonucleotide abolished the stronger inhibition of DNA replication in CPT-treated Ku80-/- cells. These results in aggregate indicated that the stronger S checkpoint in CPT-treated Ku80-/- cells is regulated through the highly activated ATR/CHK1 pathway.

Animals↗

PubMed2002

Protein inhibitor of neuronal nitric oxide synthase interacts with protein kinase A inhibitors.

Protein kinase A (PKA) and neuronal nitric oxide synthase (nNOS) are important signaling molecules. It is well known that PKA can specifically phosphorylate nNOS. But the underlying molecular mechanism is still obscure. Our data indicate that the protein inhibitor of nNOS (PIN) binds to protein kinase A inhibitors (PKIs), which suggests that PKIs, together with PIN, might mediate the phosphorylation of nNOS by PKA.

Animals↗

PubMed2002

An ATM-independent S-phase checkpoint response involves CHK1 pathway.

After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

Ataxia Telangiectasia↗

PubMed2002

Fertility after intact ovary transplantation.

Transplantation surgery, which is limited by the supply and short-term viability of fresh donor organs, would be revolutionized if these could survive freezing, but early claims of cryopreservation were never realized. Here we describe the successful transplantation in rats of ovaries, fallopian tubes and the upper segment of the uterus en bloc after storage in liquid nitrogen.

Animals↗

PubMed2002

Protective effects of ligustrazine on ischemia-reperfusion injury in rat kidneys.

To investigate the protective effects of ligustrazine on renal ischemia-reperfusion injury, the influence of ligustrazine injection on plasma superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1), as well as changes of morphology of renal tubules, were studied in rat kidney models with ischemia-reperfusion injury. The results showed that in the group treated with ligustrazine, the plasma SOD level was significantly higher than that of the control group (P < 0.05), but levels of plasma MDA and ET-1 and the pathological grading of injured renal tubules were significantly lower than those in the control group (P < 0.05). These findings suggest that ligustrazine has protective effects against ischemia-reperfusion injury in rat kidneys.

Animals↗

PubMed2002

Restoration of fertility in oophorectomized rats after tubo-ovarian transplantation.

Improved microsurgical techniques for en bloc vascularized adnexal isograft in the rat is described. The graft of the right ovary together with its fallopian tube and upper third of uterus was transplanted orthotopically with end-to-side anastomoses between the donor aortic segment and recipient aorta and between the donor vena cava segment and recipient inferior vena cava, with end-to-end anastomosis of the donor and recipient uterus in a syngeneic, bilaterally oophorectomized rat. All transplantations were successful in terms of immediate vascular patency rate (10/10, 100%). Evidence of resumed ovarian function was obtained in 9 out of 10 rats (9/10, 90.0%) by histological demonstration of the vaginal smear, in which pregnancies were achieved in six rats (6/10, 60.0%) and six litters of healthy offspring were delivered 9 weeks later after transplantation. These results suggest that microsurgical ovarian transplantation provide a new and potential experimental model for the study of fertility restoration in humans.

Anastomosis, Surgical↗

PubMed2002

[The establishment of a guinea pig model of inflammatory pleural effusion and the effect of batroxobin in the prevention of pleural encapsulation].

OBJECTIVE: To establish an animal model of inflammatory pleural effusion and to investigate the role of batroxobin in preventing encapsulation of pleural effusion. METHODS: (1) Forty guinea pigs were divided into two groups: the animal model group received injection of 1% carrageenan (0.8 approximately 1.0 ml) in the right chest cavity; the control animals received injection of normal saline (1 ml). (2) Sixty guinea pigs were injected with 1% carrageenan (0.8 approximately 1.0 ml) in the right chest cavity, and then divided into a treatment group and a control group. Batroxobin (3 BU) was injected into the right chest cavity of the animals in the treatment group, while normal saline was used in the control group. The animals were killed at different time points. RESULTS: In the animal model group, pleural effusion appeared in 24 hours and reached maximum amount within 2 approximately 3 days. Neutrophils accumulated in the effusion and pleural inflammation intensified at the same time. Fibrosis and pleural adhesion appeared by the seventh day, became prominent by the tenth day, and encapsulated pleurisy was evident by the fourteenth day. With batroxobin treatment, pleural effusion and inflammation attenuated. The fibrinogen (Fbg) level decreased, and the levels of tissue plasminogen activator (t-PA) and D-dimer increased in the effusion. No pleural encapsulation was observed. CONCLUSIONS: Carrageenan was successfully used to establish an animal model of inflammatory pleural effusion in guinea pigs. Batroxobin was effective in reducing inflammation and pleural effusion and in preventing pleural fibrosis and encapsulation.

Animals↗

PubMed2002

[Hand-assisted laparoscopic surgery in colorectal carcinoma resection: a report of 14 cases].

OBJECTIVE: To study the application of hand-assisted laparoscopic surgery (HALS) in colorectal carcinoma resection. METHODS: Fourteen patients with colorectal carcinoma underwent resection by HALS. RESULTS: Hand-assisted laparoscopic right hemicolectomy was performed in 6 of 8 ascending colon cancer patients, spending an average of 160 minutes (110 to 220 minutes) for the procedure. The amount of bleeding was 40 approximately 100 ml. Bowel sounds resumed in 36 approximately 72 hours after the operation. The average interval between the operation and patients' discharge was 8 days (7 to 12 days). For 2 patients the surgeons had to resort to laparotomy. All patients received postoperative chemotherapy. Hand-assisted laparoscopic abdominoperineal resection was performed in 5 of 6 patients with lower rectal cancer, with the average duration of 180 minutes (120 to 270 minutes), with bleeding of 40 to 80 ml. Bowel sounds resumed within 24 to 72 hours and the average discharge interval was 14 days (12 to 18 days). The urinary catheter in 6 patients was removed in 7 to 8 days after the operation. All patients with rectal carcinoma received postoperative chemotherapy and radiotherapy. One patient was shifted to laparotomy because of extensive adhesion in the pelvic cavity. Four of 11 patients treated by HALS experienced slight pain in the incision. No other complications were observed in any of the patients. Remote results await further follow-up. CONCLUSION: Hand-assisted laparoscopic surgery in the treatment of colorectal carcinoma, a safe and simple procedure, not only ensures the clearance of tumor, but also reduces operative trauma and hastens recovery.

Adult↗

PubMedDate not supplied

Axial-shear interaction effects on microdamage in bovine tibial trabecular bone.

Because many osteoporotic fractures occur during a fall, understanding the effect of off-axis loads on initiation and propagation of microdamage in trabecular bone should provide further insight into the biomechanics of age-related fractures. Fourteen on-axis cylindrical specimens were prepared from 12 bovine tibiae. Fluorescent stains were used to label the microdamage due to a sequence of compressive and torsional damaging loads. The mean decrease in Young's modulus was over four times greater than that in the shear modulus after the compressive overload, while there was no difference between the decrease in the axial and torsional stiffnesses after the torsional overload. The total microcrack density due to compression was uniform across the radius of the cylindrical specimens, while the mean density of microcracks due to torsional overloading increased from the axis of the cylindrical specimen to the circumference. The high density of microcracks near the axis of the specimen following torsional overloading was unexpected because of the low strains. Nearly 40% of the microcracks due to torsion propagated from pre-existing microcracks caused by axial compression, indicating that existing microcracks may extend at relatively low strain if the loading mode changes. The propagating microcracks were, on average, longer than the initiating microcracks due to either compressive or torsional loading. Damage due to axial compression appears to increase the susceptibility of trabecular bone to damage propagation during subsequent torsional loads, but it has little effect on the elastic properties in shear.

Animals↗

PubMedDate not supplied

CHK1-regulated S-phase checkpoint response reduces camptothecin cytotoxicity.

The cytotoxicity of camptothecin (CPT) is S phase specific and is associated with an inhibition of DNA replication. The relationship between CPT-induced inhibition of DNA replication and CPT cytotoxicity remains unclear. We previously reported that the CPT-induced inhibition reflects an activated S-phase (S) checkpoint response and that this response is mainly regulated by ATR/CHK1 pathway. In this study, by comparing A1-5 and B4, the two transformed rat embryo fibroblasts cell lines, we showed that with higher CHK1 expression, A1-5 cells had a stronger S checkpoint response and were more resistant to CPT-treatment. The data suggested that over-activated CHK1 in CPT-treated A1-5 cells regulated the strong S checkpoint response through the CDC25A/CDK2 pathway. When the CHK-1 regulated strong S checkpoint response was abolished, A1-5 cells became much more sensitive to CPT-induced killing. These data indicated that CHK1 regulated S checkpoint response protected cells from CPT-induced killing.

Animals↗