Search PubMed⌕ Search

Biomedical subjects

Jing Gao

Publications and source records attributed to Jing Gao.

At least 55 records · Page 3Linked to original sources

Protein inhibitor of activated STAT Y (PIASy) and a splice variant lacking exon 6 enhance sumoylation but are not essential for embryogenesis and adult life.

Protein inhibitor of activated STAT Y (PIASy) is the shortest member of the PIAS family and has been reported to modulate the transcriptional activities of STAT1, lymphoid enhancer factor 1 (LEF-1), and the androgen receptor. PIAS proteins have also been identified as E3 ligases for the small ubiquitin-like modifier (SUMO) proteins. PIASy in particular has been reported to mediate SUMO-2/3 modification of LEF-1, sequestering it into nuclear bodies, and SUMO-1 ligation to c-Myb, modulating its transcriptional activation properties. We have cloned murine Piasy and a splice variant which omits exon 6, containing the nuclear retention PINIT motif. Cell culture studies indicate that both the full length and the splice variant are localized in the nucleus but differentially enhance SUMO ligation. To further understand the functions of PIASy, we have generated PIASy-deficient mice. Surprisingly, Piasy(-/-) mice appear phenotypically normal. Activation of STAT1 is not significantly perturbed in Piasy(-/-) cells, and sumoylation patterns for SUMO-1 or SUMO-3 modification are similar when comparing tissues and embryonic fibroblasts from wild-type and knockout mice. Our study demonstrates that at steady state, PIASy is either dispensable or compensated for by other PIAS family members or by other mechanisms when deleted.

Alternative Splicing↗

Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage.

The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).

Alanine Transaminase↗

Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoids.

The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCl(4))-induced acute liver damage and D-galactosamine (D-GalN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7- and 2.0-fold) induced by CCl(4) were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100 mg kg(-1) TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9- and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GalN were blocked by pre-treatment with 0.05, 0.1, 0.5 g L(-1) TCCE. In addition, Ca(2+)-induced mitochondrial swelling was dose-dependently inhibited by 50-500 microM ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500 microM, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals.

Animals↗

[Progress in gene therapy of liver cirrhosis].

Liver cirrhosis is a common progressive pathological lesion in the late stage of chronic liver disease, which is characterized by disorganization of normal hepatic structure of regenerative nodules and hyperplasia of fibrotic tissues. In recent years, with the development of molecular biology, the molecular mechanisms underlying liver cirrhosis has been revealed more and more, which makes the therapy at the gene level possible. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte proliferation and reorganization of the liver architecture. Several gene therapy approaches for treatment of liver cirrhosis have been developed by transfer of some genes of cytokines and enzymes (e.g. HGF, TGF beta 1R, MMPs). These gene therapies can inhibit fibrogenesis and hepatocyte apoptosis and also produce resolution of fibrosis in the cirrhotic liver. Thus, gene therapy may be potentially useful for the treatment of liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.

Animals↗

[Changes of thioredoxin mRNA level in neurons with mitochondrial dysfunction insulted by H2O2].

Oxidative stress and mitochondrial deficiency have been considered to be associated with the mechanisms of many neurodegenerative diseases. Sodium azide (NaN3) is a special inhibitor of mitochondrion cytochrome c oxidase (COX), which can be used to mimic neuronal damage induced by mitochondrial deficiency. In this experiment, the neurotoxic effects of H2O2 on primary cultured neurons and NaN3-induced mitochondrial dysfunctional neurons were detected by means of cell viability measurement (MTT) and analyzed through morphological observation. Furthermore, the changes of thioredoxin mRNA level in both normal and abnormal cultured neurons insulted by H2O2 were analyzed by semiquantitative RT-PCR in order to explore the role of Trx, an important redox regulatory protein, in modulating the process of neuronal injury. It was found that mitochondrial dysfunctional neurons could be damaged by H2O2 in a dose- and time-dependent manner and the expression of Trx decreased during certain dose (0-200 mumol/L) and time (0-4 h) of H2O2 treatment. But in normal neurons the effects of H2O2 treatment seemed to be less evident. It suggests that in neurons with mitochondrial dysfunction, the redox modulation of thioredox seems to be more prominent.

Animals↗

[The preparation and in vitro release test of sustained release delivery gutta-percha point containing metronidazole].

PURPOSE: To develop sustained release delivery gutta-percha point containing metronidazole (SRDGM) for root canal disinfection, and determine the drug concentration in vitro and the time that the device maintains the effective drug concentration. METHODS: The gutta-percha was selected as the carrier and adsorbed metronidazole etc. The point was coated with mixation of ployethylene glycol and acetate fibre to prepare the groups of SRDGM.The group that released the longest period of the effective drug was selected for the following study. Eight teeth were selected, the SRDGM was used to disinfect the root canal. The adsorption was measured for 24 hours and 10 days. RESULTS: The SRDGM contained metronidazole 2013 microg, it could release 68.24% of the total drug in 24 hours in vitro. The effective metronidazole concentration released lasted more than 10 days. On the 10th day, there was also 33.13 microg/ml metronidazole released which was more than minitory inhibitory concentration of metronidazole. CONCLUSIONS: SRDGM could carry the metronidazole and control the release rate. It could maintain the effective drug concentration for a long time (>10 days) in root canal.

Anti-Infective Agents↗

[Protective effect of the extract of Terminalia catappa leaves on acute liver injury induced by D-GalN in mice].

OBJECTIVE: To study the hepatoprotective effect of the extract of Terminala catappa leaves (TCE) and the possible mechanisms underlying its protection on acute liver injury induced by D-Galactosamine (D-GalN). METHOD: In vivo: D-GalN-induced liver injury model was used to evaluate the effect of TCE on the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice. Structure of liver was observed and liver mitochondrial swelling was measured following D-GalN injection without or with TCE. In vitro: D-GalN-induced primary cultured hepatocytes injury model was used to value the effect of TCE on cultured hepatocytes. Cell viability was measured by means of MTT assay, and the AST and superoxide dismutase (SOD) activities in supernatant of cultured cells were investigated also. RESULT: In acute hepatic injury test, with oral pretreatment of TCE, remarkable rises in serum AST and ALT activities (2.95 fold and 3.35 fold) induced by D-GalN were obviously reversed and significant morphological changes were remarkably lessened. In addition, the decrease in sensitivity of mitochondrial swelling to the exotic Ca2+ stimulation induced by D-GalN was also prevented by TCE. In primary cultured hepatocytes of mice, it was found that incubation with TCE could prevent the decrease in cell viability in a dose-dependent manner. It was also found that both the increase in AST level (1.9 fold) and the decrease in SOD activity (48.0%) in supernatant of primary cultured hepatocytes induced by D-GalN could be inhibited by pretreatment of TCE. CONCLUSION: TCE has hepatoprotective activity and the mechanisms underlying its protective effect may be related to its antioxidant activity and protection on both hepatocytes and liver mitochondria.

Animals↗

The absorption behavior of cyclosporin A lecithin vesicles in rat intestinal tissue.

The purpose of the study was to investigate the absorption behavior of lecithin vesicles of cyclosporin A (CsA-VES), prepared by the rotary evaporation method and treated further with sonication. The everted gut sac technique and in situ circulation method were used to examine: (1) relationship between the CsA-VES absorption velocity and the CsA-VES content; (2) the influence of the intestinal mucus, blank vesicles, concentration of Na(+), energy inhibitor and P-gp inhibitor on the absorption of CsA-VES; and (3) the respective accumulated content of CsA in the incubating medium and the sacs after incubation with Sandimmum Neoral((R))(CsA-NEO) and CsA-VES. Our results showed there was a saturated absorption of CsA. Most CsA-VES accumulated in the mucus before it reached the intestinal tissue. There was no significant difference in the accumulated absorption content in the incubating medium and the sacs of CsA-NEO and CsA-VES. The addition of blank vesicles and concentration of Na(+) had no significant influence on the accumulated absorption of CsA (P>0.05). The energy inhibitor and P-gp inhibitor influenced the accumulated absorption of CsA significantly (P<0.05). CsA-VES may be transported by phagocytosis. Mucus was a barrier blocking the diffusion of CsA-VES. CsA-NEO and CsA-VES showed equal absorption levels in the intestine.

Animals↗

Laminin-10 is crucial for hair morphogenesis.

The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (alpha5beta1gamma1) in hair follicle development. Laminin-10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin-10 in hair development. Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia. E16.5 Lama5 -/- mouse skin, lacking laminin-10, contained fewer hair germs compared with controls, and after transplantation, Lama5 -/- skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 -/- skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 -/- skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin-10 in developmental signaling. Intriguingly, treatment of Lama5 -/- skin with purified laminin-10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin-10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.

Alopecia↗

Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer.

The murine Pten prostate cancer model described in this study recapitulates the disease progression seen in humans: initiation of prostate cancer with prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma, and subsequent metastasis with defined kinetics. Furthermore, while Pten null prostate cancers regress after androgen ablation, they are capable of proliferating in the absence of androgen. Global assessment of molecular changes caused by homozygous Pten deletion identified key genes known to be relevant to human prostate cancer, including those "signature" genes associated with human cancer metastasis. This murine prostate cancer model provides a unique tool for both exploring the molecular mechanism underlying prostate cancer and for development of new targeted therapies.

Animals↗

[The development and in vitro release rate determination of controlled-release delivery gutta-percha point containing metronidazole compound].

OBJECTIVE: To prepare the controlled-release delivery gutta-percha points containing metronidazole compound (CDGMC) and to determine its release rate in vitro. METHODS: The drug points were made by using compound drugs and gutta-percha as a carrier, and CDGMC were prepared followed by enveloping a release membrane outward. The best formula was selected according to the release parameters of the drugs extracted in the release experiments in vitro. The CDGMC were placed into the extracted teeth after root canals were routinely prepared. The non-drug CDGMC was used as the control. The absorbency of the drugs in normal saline (37 degrees C, pH 7.4) was determined timely. The percentage of release and cumulated release of the drugs were calculated according to the concentrations of drugs in medium. RESULTS: The in vitro experiments showed that this system contained 1,880 micrograms of metronidazole and 267 micrograms of ciprofloxacin. The experiments in healthy single root canal showed that the drug release amounts around the perioapical area were metronidazole 88.54 micrograms/ml and ciprofloxacin 9.05 micrograms/ml in 10 days. CONCLUSION: CDGMC can continuously release effective drug concentrations more than 10 days and could be considered as an ideal method for clinical application.

Anti-Infective Agents, Local↗

[Hepatoprotective effects of chloroform extract from leaf of Terminalia catappa in relation to the inhibition of liver IL-6 expression].

OBJECTIVE: To study the hepatoprotective effects of Terminalia catappa chloroform extract (TCCE) and its effects on IL-6 gene over expression in liver of CCl4-treated mice. METHOD: Mice were orally pretreated with TCCE (20, 50, 100 mg x kg(-1) x d(-1)) for 5 days, and the sALT activity of mice was detected 24 hours after the intraperitoneal injection of CCl4 on the 5 th day. Meanwhile, IL-6 mRNA level was determined by using the method of RT-PCR. And the liver morphological changes were also observed. RESULT: sALT activity was remarkably increased (5.6 fold) after the injection of CCl4. However, with oral pretreatment of TCCE, changes in sALT were dose-dependently reversed. On the other hand, significant increase in IL-6 mRNA level induced by CCl4 was remarkably decreased. The level of IL-6 mRNA in 100 mg x kg(-1) TCCE treated mice was reversed to that of control. In addition, histological changes such as the infiltration of numerous inflammatory cells and hepatocyte swelling in injured mice were effectively lessened by the pretreatment of TCCE. CONCLUSION: TCCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the inhibition on the over expression of IL-6 gene in liver.

Alanine Transaminase↗

Interferon type I downregulates human parainfluenza virus type 3-induced major histocompatibility complex class II expression.

Human parainfluenza virus type 3 (HPIV3) induces major histocompatibility complex (MHC) class II expression in a signal transducer and activator of transcription-1 (STAT1)- and class II transactivator (CIITA)-independent manner. Interferon (IFN)-gamma, the potent inducer of MHC class II, on the other hand, requires both STAT1 and CIITA in the induction process. IFN-alpha/beta has been shown to inhibit the IFN-y-induced expression of MHC class II by targeting a step(s) downstream of CIITA. Here we report that IFN-alpha/beta also inhibits the CIITA-independent expression of HPIV3-induced MHC class II. The inhibitory role of IFN-alpha/beta on HPIV3-induced MHC class II was confirmed by using anti-IFN-alpha/beta antibody and mutant cell lines defective in the IFN signaling components STAT1 and STAT2. IFN-alpha/beta inhibits virus-induced MHC class II expression just as it does IFN-gamma-induced MHC class II. The inhibition by IFN-alpha/beta of MHC class II expression may play a regulatory role in virus induced autoimmune disease mediated by MHC class II aberrant expression.

Animals↗

Isolation of mouse THP gene promoter and demonstration of its kidney-specific activity in transgenic mice.

Tamm-Horsfall protein (THP), the most abundant urinary protein synthesized by the kidney epithelial cells, is believed to play important and diverse roles in the urinary system, including renal water balance, immunosuppression, urinary stone formation, and inhibition of bacterial adhesion. In the present study, we describe the isolation of a 9.3-kb, 5'-region of the mouse THP gene and show the highly conserved nature of its proximal 589-bp, 5'-flanking sequence with that in rats, cattle, and humans. We also demonstrate using the transgenic mouse approach that a 3.0-kb, proximal 5'-flanking sequence is sufficient to drive the kidney-specific expression of a heterologous reporter gene. Within the kidney, transgene expression was confined to the renal tubules that endogenously expressed the THP protein, which suggests specific transgene activity in the thick ascending limb of the loop of Henle and early distal convoluted tubules. Our results establish the kidney- and nephron-segment-specific expression of the mouse THP gene. The availability of the mouse THP gene promoter that functions in vivo should facilitate additional studies of the molecular mechanisms of kidney-specific gene regulation and should provide new molecular tools for better understanding renal physiology and disease through nephron-specific gene targeting.

Animals↗

[Congenital absence of the vagina in 126 patients].

OBJECTIVES: To investigate the clinical features and therapeutic results of multiple approaches for congenital absence of the vagina, and to find out the prevention of complications and reconstruction method. METHODS: We analysed retrospectively 126 patients with congenital absence of the vagina from 1979 to 2002. RESULTS: Congenital absence of the vagina occurred in 31.25% urinary tract anomalies and 6.35% musculoskeletal anomalies. Of the 126 patients, 6 received 2 or more than 2 operations, the remaining recovered after reconstruction of the vagina by using the inferior abdominal wall skin flap and pudendal-thigh skin flap. CONCLUSIONS: The techniques should be selected according to the conditions of the patient and features of multiple approaches. Damage to the rectum and urinary tract should be avoided in addition to postoperative retraction or prolapse of flaps and stenosis of the vaginal orifice.

Adolescent↗

[Repair of large facial defect with an expanded clavicular-pectoral skin flap].

OBJECTIVE: To search for an ideal method to repair large facial defects. METHODS: One or two soft tissue expanders were implanted at the clavicular-pectoral region. After fully expansion, a clavicular-pectoral skin flap was designed and created with similar color, texture, and size to the facial defect. The flap would pass over the neck and transfer to the face to repair a large defect. RESULTS: 10 cases were treated with this method. All have been followed up for 12-18 months with satisfactory results. CONCLUSION: The large facial defects could be repaired by the expanded clavicular-pectoral skin flap without damaging the natural neck contour and donor site abnormality was avoided. The patients get an aesthetic look and good function.

Adolescent↗