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Biomedical subjects

M Jiang

Publications and source records attributed to M Jiang.

At least 19 recordsLinked to original sources

Global analysis of differentially expressed genes in androgen-independent prostate cancer.

Progression to androgen independent (AI) is the main cause of death in prostate cancer, and the mechanism is still unclear. By reviewing the expression profiles of 26 prostate cancer samples in a holistic view, we found a group of genes differentially expressed in AI compared with androgen-dependent groups (P-value<0.01, t-test). Focusing on apoptosis, proliferation, hormone and angiogenesis, we found a group of genes such as thioredoxin domain containing 5 , tumor necrosis factor receptor superfamily, member 10a , ribosomal protein S19 and Janus kinase 2 upregulated in AI prostate cancer, could play important roles in the transition from AD to AI and could be biomarkers of prognosis.

Androgen Antagonists↗

Improvement of peripheral nerve regeneration by a tissue-engineered nerve filled with ectomesenchymal stem cells.

Ectomesenchymal stem cells (EMSCs) originate from the cranial neural crest. They are a potential source of neuronal and Schwann cells (SCs) of the peripheral nervous system (PNS) during embryonic development. The third passage of EMSCs enzymatically isolated from the mandibular processes of Sprague-Dawley rats were cultured in forskolin and bovine pituitary extract for 6 days to generate functional Schwann cell phenotypes. Next, 10-mm defects in the sciatic nerves were bridged with an autograft, tissue-engineered nerve filled with differentiated cells in collagen, or a PLGA conduit alone in 18 rats, and the nerve defects of another four rats were left untreated. The regenerated nerves were evaluated by the sciatic functional index (SFI) monthly and by histological analysis 4 months after grafting. The recovery index of the sciatic nerve improved significantly in the autograft and tissue-engineered nerve groups, both of which were superior to the PLGA group. In animals transplanted with the EMSCs, there was greater regeneration than with conduit alone during the same period of implantation. These results show that when EMSCs are transplanted to a peripheral nerve defect they differentiate into supportive cells that contribute to the promotion of axonal regeneration.

Absorbable Implants↗

Regulation of PUMA-alpha by p53 in cisplatin-induced renal cell apoptosis.

Nephrotoxicity is a major side effect of cisplatin, a widely used cancer therapy drug. Depending on its concentration, cisplatin induces necrosis or apoptosis of tubular cells in the kidneys, whereas the underlying injury mechanism is unclear. Our recent work has suggested a critical role for p53 in cisplatin-induced tubular cell apoptosis; nevertheless, the apoptotic events triggered by p53 remain elusive. The current study has examined Bcl-2 family proteins, critical regulators of apoptosis that may be subjected to p53 regulation. Following cisplatin treatment, the expression of Bcl-xL, an antiapoptotic molecule, was suppressed, while the expression of Bak, a proapoptotic molecule, increased slightly. Of interest, PUMA-alpha, a newly identified p53-responsive proapoptotic Bcl-2 family protein, was drastically induced by cisplatin. PUMA-alpha induction preceded or paralleled the development of apoptosis. Induced PUMA-alpha was localized in mitochondria and appeared to antagonize Bcl-xL via molecular interaction. PUMA-alpha induction during cisplatin treatment was attenuated by pifithrin-alpha, a pharmacological inhibitor of p53, which was accompanied by the amelioration of Bax activation, cytochrome c release and apoptosis. Moreover, PUMA-alpha induction was suppressed by dominant-negative p53. Importantly, cisplatin-induced apoptosis was ameliorated in PUMA-alpha knockout cells. In vivo, cisplatin induced PUMA-alpha in the kidneys, and the inductive response was abrogated in p53-deficient animals. Together, this study has demonstrated the first compelling evidence for the involvement of PUMA-alpha in p53-mediated renal cell apoptosis during cisplatin nephrotoxicity.

Animals↗

A theoretical and experimental study of lead substitution in calcium hydroxyapatite.

Characterization of lead substitution for calcium in hydroxyapatite (CaHA) is carried out, using experimental techniques and Density Functional theoretical (DFT) analyses. Theoretical modeling is used to obtain information of the Pb chemical environment for occupancy at either Ca(I) or Ca(II) sites of CaHA. Effects of the larger ionic radius of Pb(+2) compared to Ca(+2) are apparent in embedded cluster calculations of local chemical bonding properties. DFT periodic planewave pseudopotential studies are used to provide first-principles predictions of local structural relaxation and site preference for Pb(x)Ca(10-x)HA over the composition range x< or = 6. General characteristics of the polycrystalline material are verified by X-ray diffraction and FTIR analysis, showing the presence of a single phase of CaHA structure. A short range structure around lead is proposed in order to interpret the Pb L-edge EXAFS spectrum of the solid solution Ca(6.6)Pb(3.4)HA. In this concentration we observe that lead mainly occupies Ca(II) sites; the EXAFS fit slightly favors Pb clustering, while theory indicates the importance of Pb-Pb avoidance on site (II).

Biocompatible Materials↗

Effects of alpha-melanocyte-stimulating hormone on magnocellular oxytocin neurones and their activation at intromission in male rats.

The peptides alpha-melanocyte-stimulating hormone (alpha-MSH) and oxytocin have very similar effects on several behaviours, including male sexual behaviour. Both induce penile erection and enhance copulatory behaviour when given centrally, suggesting that their central actions are not independent. Here, we used intromission as a physiological stimulus to investigate whether some central effects of alpha-MSH during male sexual behaviour are mediated by oxytocin neurones. We used the expression of the immediate-early gene product Fos to investigate oxytocin neurone activation at intromission and after intracerebroventricular (i.c.v.) administration of alpha-MSH (1 microg/5 microl) and studied the effects of i.c.v. administration of a MC4 receptor antagonist on Fos expression and on the latency of male rats to exhibit sexual behaviour in the presence of a receptive female. In rats that showed intromission, Fos was expressed in magnocellular oxytocin neurones in both the paraventricular nucleus (PVN) and the supraoptic nucleus (SON), but there was no significant activation of parvocellular oxytocin neurones of the PVN. Similarly, alpha-MSH increased Fos expression in magnocellular oxytocin neurones but had little or no effect in parvocellular oxytocin neurones. In male rats that achieved intromission, central injection of a MC4 receptor antagonist significantly attenuated the increase in Fos expression in magnocellular oxytocin neurones in both the PVN and the SON and increased mount and intromission latencies compared to vehicle-injected controls. Together, the results indicate that magnocellular oxytocin neurones are involved in the central regulation of male sexual behaviour, and that some of the central effects of alpha-MSH are likely to be mediated by magnocellular oxytocin neurones.

Animals↗

Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study.

To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0.05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.

Adult↗

HIV and syphilis in migrant workers in eastern China.

OBJECTIVE: To measure the prevalence of HIV and syphilis in migrant and urban workers in eastern China, and to determine their knowledge and attitudes towards HIV. METHODS: A cross sectional survey involving dried blood spot testing and self completion questionnaires. Migrants and urban workers in 39 work units in two districts of Hangzhou, Zhejiang Province, were recruited. Respondents completed a questionnaire about knowledge and attitudes towards HIV. Testing for antibodies to HIV-1 and syphilis was carried out on dried blood spots using a gelatin particle agglutination technique. RESULTS: Data were obtained from 4148 migrants and 2197 urban workers. There were no HIV infections detected in either the migrant or urban populations. Syphilis was detected, but the prevalence was not significantly different between urban workers (0.68%, 95% CI: 0.35 to 1.02) and migrant workers (0.48%, 95% CI 0.26 to 0.66, p = 0.07). 36% of the migrants had migrated with a partner, and 7% had also migrated with children. Urban workers were consistently more knowledgeable than migrants about HIV, but knowledge of the major modes of transmission was good in both groups. Traditional attitudes to sexual behaviour were still pervasive in both groups and attitudes towards individuals with HIV were generally intolerant. The use of sex workers appears rare and no more common in migrants than urban workers. CONCLUSION: At present HIV is probably not spreading in the internal migrant population in eastern China. Syphilis is a problem in both the migrant and urban populations. The tendency to migrate with partners makes migrants relatively low risk for engaging in casual sex.

Adolescent↗

A role for L-type calcium channels in the maturation of parvalbumin-containing hippocampal interneurons.

While inhibitory interneurons are well recognized to play critical roles in the brain, relatively little is know about the molecular events that regulate their growth and differentiation. Calcium ions are thought to be important in neuronal development and L-type voltage gated Ca(+2) channels have been implicated in activity-dependent mechanisms of early-life. However, few studies have examined the role of these channels in the maturation of interneurons. The studies reported here were conducted in hippocampal slice cultures and indicate that the L-type Ca(+2) channel agonists and antagonists accelerate and suppress respectively the growth of parvalbumin-containing interneurons. The effects of channel blockade were reversible suggesting they are not the result of interneuronal cell death. Results from immunoblotting showed that these drugs have similar effects on the expression of the GABA synthetic enzymes, glutamic acid decarboxylase65, glutamic acid decarboxylase67 and the vesicular GABA transporter. This suggests that L-type Ca(+2) channels regulate not only parvalbumin expression but also interneuron development. These effects are likely mediated by actions on the interneurons themselves since the alpha subunits of L-type channels, voltage-gated calcium channel subunit 1.2 and voltage-gated calcium channel subunit 1.3 were found to be highly expressed in neonatal mouse hippocampus and co-localized with parvalbumin in interneurons. Results also showed that while these interneurons can contain either subunit, voltage-gated calcium channel subunit 1.3 was more widely expressed. Taken together results suggest that an important subset of developing interneurons expresses L-type Ca(+2) channels alpha subunits, voltage-gated calcium channel subunit 1.2 and especially voltage-gated calcium channel subunit 1.3 and that these channels likely regulate the development of these interneurons in an activity-dependent manner.

Animals↗

Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.

Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.

Amino Acid Sequence↗

Functional role of RXRs and PPARgamma in mature adipocytes.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is abundantly expressed in adipocytes, and plays an important role in adipocyte differentiation and fat accretion. It is a heterodimeric partner of the retinoid X receptors alpha, beta and gamma, which are also expressed in the adipose tissue. As lethality of PPARgamma(-/-) and RXRalpha(-/-) mouse fetuses precluded the analysis of PPARgamma and RXRalpha functions in mature adipocytes, we generated RXRalpha(ad-/-) and PPARgamma(ad-/-) mice, in which RXRalpha and PPARgamma are selectively ablated in adult adipocytes, respectively. Even though the adiposity of RXRalpha(ad-/-) mice is similar to that of control mice when fed a regular diet, they are resistant to chemically and dietary-induced obesity. However, mature adipocytes lacking either both RXRalpha and RXRgamma or PPARgamma die, and are replaced by newly formed adipocytes. Thus, in adipocytes, RXRalpha is essential for lipogenesis, but RXRgamma can functionally replace RXRalpha for the adipocyte vital functions exerted by PPARgamma/RXR heterodimers.

Adipocytes↗

Coordinate downregulation of CaM kinase II and phospholamban accompanies contractile phenotype transition in the hyperthyroid rabbit soleus.

This study investigated the effects of l-thyroxine-induced hyperthyroidism on Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaM kinase II)-mediated sarcoplasmic reticulum (SR) protein phosphorylation, SR Ca(2+) pump (Ca(2+)-ATPase) activity, and contraction duration in slow-twitch soleus muscle of the rabbit. Phosphorylation of Ca(2+)-ATPase and phospholamban (PLN) by endogenous CaM kinase II was found to be significantly lower (30-50%) in soleus of the hyperthyroid compared with euthyroid rabbit. Western blotting analysis revealed higher levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 1 ( approximately 150%) Ca(2+) pump isoform, unaltered levels of SERCA2 Ca(2+) pump isoform, and lower levels of PLN ( approximately 50%) and delta-, beta-, and gamma-CaM kinase II (40 approximately 70%) in soleus of the hyperthyroid rabbit. SR vesicles from hyperthyroid rabbit soleus displayed approximately twofold higher ATP-energized Ca(2+) uptake and Ca(2+)-stimulated ATPase activities compared with that from euthyroid control. The V(max) of Ca(2+) uptake (in nmol Ca(2+).mg SR protein(-1).min(-1): euthyroid, 818 +/- 73; hyperthyroid, 1,649 +/- 90) but not the apparent affinity of the Ca(2+)-ATPase for Ca(2+) (euthyroid, 0.97 +/- 0.02 microM, hyperthyroid, 1.09 +/- 0.04 microM) differed significantly between the two groups. CaM kinase II-mediated stimulation of Ca(2+) uptake by soleus muscle SR was approximately 60% lower in the hyperthyroid compared with euthyroid. Isometric twitch force of soleus measured in situ was significantly greater ( approximately 36%), and the time to peak force and relaxation time were significantly lower ( approximately 30-40%), in the hyperthyroid. These results demonstrate that thyroid hormone-induced transition in contractile properties of the rabbit soleus is associated with coordinate downregulation of the expression and function of PLN and CaM kinase II and selective upregulation of the expression and function of SERCA1, but not SERCA2, isoform of the SR Ca(2+) pump.

Animals↗

Auxiliary liver-heart transplantation in the rat: a new microsurgical model inducing tolerance.

OBJECTIVE: To establish a model of immunological tolerance induced by simultaneous auxiliary liver transplantation and heterotopic heart transplantations using PVG and DA rats as donors and recipients respectively, to provide a new method for the research of liver transplantation. METHODS: The recipient's whole portal vein blood was transfered to the auxiliary liver allograft. The donor's heart was transplanted to the recipient's abdominal cavity by end-to-side anastomosis of the donor aorta and pulmonary artery to the recipient aorta and vena cava, respectively. RESULTS: In the syngeneic control group and the test group the recipient rats and their transplanted hearts both survived more than 100 days, while the hearts of alloheart control group only survived 6 days. The weight of the liver graft increased slowly. CONCLUSIONS: In the presence of recipient liver, the auxiliary liver graft functioned well to induce tolerance. At 100 days, the auxiliary liver graft had increased in volume and weight with maintenance of its tolerance-inducing effects.

Animals↗

High Ca(2+)-phosphate transfection efficiency enables single neuron gene analysis.

Introducing exogenous genes into cells is one of the most important molecular techniques to study gene functions. Comparing to other type of cells, neurons are more difficult to transfect with cDNAs because they are very sensitive to microenvironmental changes. Among various gene transfer techniques, the Ca(2+)-phosphate transfection method is one of the most popular tools in neuroscience research because of its low cell toxicity and easiness to use. However, it is well known that the Ca(2+)-phosphate transfection efficiency in neurons is very low, typically in the range of 1-5%, which has limited its applications in gene functional analyses. Here we report a novel Ca(2+)-phosphate transfection protocol that dramatically increased the transfection efficiency by 10-fold, up to 60%, while maintaining low cell toxicity. The critical factors are the formation of homogenous snow-like precipitate with particle size about 1-3 microm and the subsequent removal of the precipitate. Using this new transfection protocol, we were able to routinely transfect single autaptic neurons in hippocampal microisland cultures and combine it with electrophysiology and fluorescent imaging methods to study gene functions. This high efficiency, low toxicity, and simple to use gene transfer method will have a broad application in gene research at the single cell level.

Animals↗

The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma.

PURPOSE: Although deletions or inactivating mutations of the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) are involved in the development of a variety of tumors including glioblastoma, melanoma, prostate cancer, breast cancer, endometrial cancers etc., the role of PTEN expression in human primary hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to investigate the involvement of PTEN mRNA and protein expression in HCC. METHODS: The level of PTEN mRNA expression in HCC specimens was analyzed by Northern blot. PTEN poly-clonal antibody was raised by immunizing New Zealand white rabbit with (His)(6)-tagged PTEN fusion protein and characterized by Western blot. The level of PTEN protein expression was determined by immunohistochemistry. The significance of PTEN in HCC was analyzed by comparing its expression level with the clinicopathological parameters of HCC patients. RESULTS: Four transcripts of PTEN mRNA at 5.5 kb, 4.4 kb, 2.4 kb, and 1.8 kb were detected in most para-carcinoma liver tissues, and the expression level of PTEN mRNA in carcinoma liver tissues was found to decrease significantly. The poly-clonal antibody raised against histidine-tagged fusion PTEN protein showed specific immuno-reactivity to PTEN protein. Using the specific poly-clonal antibody prepared and characterized by ourselves, we found that PTEN protein was significantly down-regulated in HCC tissues compared with paired para-carcinoma tissues. The protein expression of PTEN is negatively associated with the pathological grading and presence of cancer thrombus of HCC. CONCLUSIONS: Down-regulation of PTEN expression may play an important role in the development of HCC and the level of PTEN expression may be a potential adjuvant parameter in forecasting the progression and prognosis of HCC patients.

Carcinoma, Hepatocellular↗

Seismic images of crust and upper mantle beneath Tibet: evidence for Eurasian plate subduction.

Seismic data from central Tibet have been combined to image the subsurface structure and understand the evolution of the collision of India and Eurasia. The 410- and 660-kilometer mantle discontinuities are sharply defined, implying a lack of a subducting slab beneath the plateau. The discontinuities appear slightly deeper beneath northern Tibet, implying that the average temperature of the mantle above the transition zone is about 300 degrees C hotter in the north than in the south. There is a prominent south-dipping converter in the uppermost mantle beneath northern Tibet that might represent the top of the Eurasian mantle lithosphere underthrusting the northern margin of the plateau.

Journal Article↗

Usefulness of automatic detection of fragmented red cells using a hematology analyzer for diagnosis of thrombotic microangiopathy.

We previously reported an automatic method for quantitative analysis of schistocytes or fragmented red cells using an automatic hematology analyzer, XE-2100. In the study reported here, we evaluated the accuracy of this detection method in patients with thrombotic microangiopathy (TMA). A follow-up study was performed on 14 patients with two types of TMA, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Schistocyte percent was evaluated both with an automatic counter and by means of microscopic observation. Total activity and isoenzyme pattern of lactate dehydrogenase (LD) were also determined. In these patients, schistocyte percent determined by automatic counting correlated highly with that determined by manual counting under microscopic observation (r = 0.852, P < 0.0001). Schistocyte percent was shown to correlate significantly with isoenzyme fractions 1 and 2 of LD (r = 0.732, P < 0.02), reflecting hemolysis. Nine of 11 patients tested had high concentrations of LD isoenzyme five without distinct liver damage, and schistocyte percent did not relate to fraction 5 of LD. Automatic detection of schistocyte percent using a hematology analyzer was useful for an accurate diagnosis and follow-up of thrombotic microangiopathy. The origin of LD fraction 5 remains to be determined.

Adult↗

Isolation and characterization of a human novel RAB (RAB39B) gene.

Rab proteins are small-molecular-weight GTPases that control vesicular trafficking in eukaryotic cells. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone encoding a novel Rab protein, which showed 74.2% identity with previously isolated Rab39A at the amino acid level. RAB39B was expressed in a variety of human tissues and located in human chromosome Xq28. It consisted of two exons spanning 3764 bp of human genomic DNA.

Adult↗

Molecular cloning and characterization of a novel human gene (ANP32E alias LANPL) from human fetal brain.

Leucine-rich acidic nuclear protein (LANP) is a member of the leucine-rich repeats (LRRs) superfamily. Here we report on a human homologue of LANP, encoded by the gene ANP32E (alias LANPL). The gene was cloned and identified during large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 70% amino acid identity with rat LANP. According to bioinformatics analysis, ANP32E is located on chromosome 1q22. RT-PCR analysis indicates that ANP32E was expressed in human peripheral blood leukocytes, colon, small intestine, prostate, thymus, spleen, skeletal muscle, liver and kidney.

Amino Acid Sequence↗