Search PubMed⌕ Search

Biomedical subjects

X Zhu

Publications and source records attributed to X Zhu.

At least 145 records · Page 8Linked to original sources

A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.

Alzheimer Disease↗

A large-scale analysis of mRNAs expressed by primary mesenchyme cells of the sea urchin embryo.

The primary mesenchyme cells (PMCs) of the sea urchin embryo have been an important model system for the analysis of cell behavior during gastrulation. To gain an improved understanding of the molecular basis of PMC behavior, a set of 8293 expressed sequenced tags (ESTs) was derived from an enriched population of mid-gastrula stage PMCs. These ESTs represented approximately 1200 distinct proteins, or about 15% of the mRNAs expressed by the gastrula stage embryo. 655 proteins were similar (P<10(-7) by BLAST comparisons) to other proteins in GenBank, for which some information is available concerning expression and/or function. Another 116 were similar to ESTs identified in other organisms, but not further characterized. We conservatively estimate that sequences encoding at least 435 additional proteins were included in the pool of ESTs that did not yield matches by BLAST analysis. The collection of newly identified proteins includes many candidate regulators of primary mesenchyme morphogenesis, including PMC-specific extracellular matrix proteins, cell surface proteins, spicule matrix proteins and transcription factors. This work provides a basis for linking specific molecular changes to specific cell behaviors during gastrulation. Our analysis has also led to the cloning of several key components of signaling pathways that play crucial roles in early sea urchin development.

Animals↗

Recent discoveries in physiology of insulin-like growth factor-1 and its interaction with gonadotropins in folliculogenesis.

Ovarian follicular development is under the influence of gonadotrophins. The manner by which gonadotrophins achieve their role in cell replication and hormone production is through other specialized molecules. Insulin-like growth factor-1 (IGF-1) is considered to be one of the most important of these molecules. IGF-1 is present in relatively large amounts in the ovary and the IGF-1 gene is expressed in the graafian follicle. IGF-1 binding proteins modulate the action of IGF-1 and are influenced by gonadotrophins. Null mutations of genes encoding IGF-1 and type-1 IGF receptor have demonstrated the obligatory role of IGF-1 in folliculogenesis. It was proposed that IGF-1 may be an obligatory mediator of gonadotrophin-induced folliculogenesis and that the interaction is synergistic. From this point, one group embarked on a series of physiological studies to further elucidate the interaction of these molecules. We discovered that, according to circumstances, follicle stimulating hormone (FSH) may act with IGF-1 synergistically (as was postulated before), additively, independently, or even antagonistically. We discovered that granulosa cells must first be exposed to FSH and then they respond well to IGF-1. All previous studies of granulosa cells were done on mural granulosa cells. We subsequently showed that cumulus type of granulosa cells (adjacent to the oocyte) behave differently in their responses to gonadotrophins and IGF-1.

Animals↗

Sensory neuroanatomy of a passively ingested nematode parasite, Haemonchus contortus: amphidial neurons of the third-stage larva.

The sensory neuronal ultrastructure of the amphids of the infective larva (L3) of Haemonchus contortus was analyzed, compared, and contrasted with that of the first-stage larva (L1). As in L1, each amphid of the L3 is innervated by 12 neurons. Thirteen ciliated dendritic processes of 10 neurons, 3 with double processes, lie in each amphidial channel. The dendritic process of each finger cell neuron ends in a large number of digitiform projections or "fingers," many more than in the L1. Processes of another pair of specialized neurons, probable homologs of wing cells in Caenorhabditis elegans, extend into the extreme anterior tip of the larva; they are much longer than those in L1. In L3, the neurons exit through the posterior wall of the amphidial chamber individually rather than in a bundle, as in L1. Cell constancy between L1 and L3 was confirmed, and the neurons were individually identified. Significant neuron-specific variations, presumably related to functional differences between the 2 stages were observed. In contrast, species-specific differences are surprisingly small. Haemonchus contortus is closely related to hookworms and has amphidial structure nearly identical to that in hookworms and similar to that in C. elegans, to which it is also closely related.

Animals↗

Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer.

PURPOSE: Scatter factor (SF), also known as hepatocyte growth factor (HGF), has been shown to induce proliferation, scattering and invasiveness in human prostate cancer cell lines. In this study we determined the serum level of SF-HGF in men with metastatic prostate cancer compared to those with localized prostate cancer and without prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from men with biopsy proved adenocarcinoma of the prostate and radiographic evidence of metastatic disease, those with biopsy proved adenocarcinoma of the prostate and clinically localized disease, and those with negative sextant prostate biopsies. Serum SF-HGF was determined using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Of the 108 men enrolled in our study 52 had negative sextant biopsies, 36 had clinically localized cancer and 20 had metastatic disease. The serum level in men with metastatic disease was significantly elevated (mean 2,117 pg./ml., range 820 to 6,403) compared to that in men with localized cancer and without prostate cancer (mean 974 pg./ml., range 437 to 2,132 and 700, range 272 to 1,875, respectively, p = 9.5 x 10(-15)). Logistic regression analysis demonstrated that the association of ln (SF-HGF) with prostate cancer persisted after controlling for patient age and ln (prostate specific antigen) (p = 3.1 x 10(-4)). CONCLUSIONS: Serum SF-HGF is increased in men with metastatic prostate cancer. SF-HGF levels are associated with metastatic prostate cancer independent of the prostate specific antigen level and patient age. These data imply that SF-HGF may be an important serum marker for prostate cancer.

Adenocarcinoma↗

Genetic approach to insight into the immunobiology of human dendritic cells and identification of CD84-H1, a novel CD84 homologue.

To better understand the immunobiology of dendritic cells (DCs), we took the expressed sequence tag (EST) approach to describe their transcript profile and discovered novel genes. ESTs (n = 25,668) were generated from monocyte-derived DCs, and 15,863 ESTs (61.8%) represented unique genes in GenBank. Integration of ESTs allowed for the generation of a profile of 4,367 known genes and identification of > 100 novel genes. HLA-DR invariant chain p33, cathepsin D, HLA-DR alpha chain, beta2-microglobulin, HLA-DP beta chain, CD11a, and mannose receptor were in the top 30 transcripts, and 451 known genes were potentially associated with the immunobiology of DCs. This transcript profile was consistent with the unique antigen-presenting capacity of DCs and provided invaluable information to better understand the immunobiology of DCs. On the basis of the EST database, a full-length novel gene was identified that exhibited close homology with CD84; it was designated CD84-H1. The full-length cDNA of CD84-H1 contained an open reading frame of 870 bp encoding a type I transmembrane protein of 289 amino acids. Consistent with the structural feature of the CD2 family, the predicted 270-amino acid mature protein of CD84-H1 contained two extracellular immunoglobulin-like domains that shared homology with CD2 family members, e.g., CD84, Ly-9, CD48, and signaling lymphocyte activation molecule. Its intracellular domain was short and contained no putative signaling structure. Northern blot analysis revealed that CD84-H1 expression was predominantly restricted in hematopoietic tissues. Reverse transcription-PCR analysis showed that it was widely expressed in the immune cells, including monocytes, DCs, B cells, and T cells. These data indicate that CD84-H1 may be relevant to immune responses.

Adult↗

Biofilm structure and mass transfer in a gas phase trickle-bed biofilter.

Mass transport phenomena occurring in the biofilms of gas phase trickle-bed biofilters are investigated in this study. The effect of biofilm structure on mass transfer mechanisms is examined using experimental observation from the operating of biofilters, microelectrode techniques and microscopic examination. Since the biofilms of biofilters used for waste gas treatment are not completely saturated with water, there is not a distinguishable liquid layer outside the biofilm. Results suggest that due to this characteristic, gas phase substrates (such as oxygen or volatile organic compounds) may not be limited by the aqueous phase because transport of the compound into the biofilm can occur directly through non-wetted areas. On the other hand, for substrates that are present only in the liquid phase, such as nitrate, the mass transfer limitation is more serious because of the limited liquid supply. Microscopic observations show that a layered structure with void spaces exists within the biofilm. Oxygen concentration distributions along the depth of the biofilms are examined using an oxygen microelectrode. Results indicate that there are some high dissolved oxygen zones inside the biofilm, which suggests the existence of passages for oxygen transfer into the deeper sections of the biofilm in a gas phase trickle-bed biofilter. Both the low gas-liquid mass transfer resistance and the resulting internal structure contribute to the high oxygen penetration within the biofilms in gas phase trickle-bed biofilters.

Biofilms↗

Effects of mechanical stretching on trabecular matrix metalloproteinases.

PURPOSE: The homeostatic mechanisms responsible for intraocular pressure (IOP) regulation are not understood. Studies were conducted to evaluate the hypothesis that trabecular meshwork (TM) cells sense increases in IOP as stretching or distortion of their extracellular matrix (ECM) and respond by increasing ECM turnover enzymes. METHODS: Flow rates were increased in perfused human anterior segment organ cultures and the matrix metalloproteinase (MMP) levels and IOP were evaluated. Human TMs in stationary anterior segment organ culture were mechanically stretched, and MMP levels were analyzed. TM cells were grown on membranes, which were then stretched, and MMP levels were evaluated. Western immunoblots, zymography, and confocal immunohistochemistry were used to evaluate changes in MMPs and their tissue inhibitors, the TIMPS: RESULTS: Doubling the flow rate in perfused human organ cultures increased gelatinase A levels in the perfusate by 30% to 50% without affecting gelatinase B or stromelysin levels. Immediately after doubling the flow rate, the measured IOP doubled. However, over the next few days the IOP gradually returned to the initial level, although the flow rate was maintained at double the initial value. Stretching stationary organ cultures or stretching TM cells grown on membranes resulted in similar increases in gelatinase A without changes in gelatinase B or stromelysin levels. The gelatinase A increases occurred between 24 and 72 hours and were approximately proportional to the degree of stretching. Although coating the membranes with different ECM molecule affected the gelatinase A response, the optimum response occurred when the cells had been grown long enough to produce their own ECM. By Western immunoblot and confocal immunohistochemistry, the stretch-induced increases in gelatinase A were accompanied by strong decreases in TIMP-2 levels and moderate increases in one membrane type MMP, MT1-MMP. After mechanical stretching of the membrane, gelatinase A, MT1-MMP and TIMP-2 all exhibited a similar punctate immunostaining pattern over the TM cell surface. CONCLUSIONS: These results are compatible with the hypothesis that elevations in IOP are sensed by TM cells as ECM stretch/distortion. TM cells respond by increasing gelatinase A and MT1-MMP, while decreasing TIMP-2 levels. This will increase ECM turnover rates, reduce the trabecular resistance to aqueous humor outflow, and restore normal IOP levels. This hypothesis provides a regulatory feedback mechanism for IOP homeostasis.

Animals↗

[Ecological analysis and optimization design for agricultural landscape of coastal zone along Radial Submarine Sand Ridges in north Jiangsu].

The Radial Submarine Sand Ridges (RSSR) on the inner shelf of the Southwestern Yellow Sea is one of the largest of such system in the world. It was developed into great amount of land which is mainly used for agriculture. However, the coastal zone is facing many serious environmental and resources problems such as coastal erosion, ecological fragility and over- and abuse of coastal resources. Based on comprehensive field survey, this paper proposes optimization allocation and design of agri-landscape spatial structures targeting an integrated improvement in agricultural ecology, economy and amenity of the region as well as implementation of sustainable development strategy. As a case study, rectification approaches and conceptual optimization design for Rudong County are proposed and discussed.

Agriculture↗

[Therapeutic potential of recombinant adenovirus expressing p53 in hepatocellular carcinoma cell lines].

OBJECTIVE: To investigate the effects of the recombinant adenoviral vector Ad-p53 on the biological behavior of hepatocellular carcinoma (HCC) cells in vitro and in vivo. METHODS: With recombinant adenoviral vector expressing WT-p53 (Ad-p53), p53 gene was transfected into the HCC cell line, PLC/PRF/5. The cytotoxicities of Ad-p53 to cells were measured by MTT assay. Cell growth properties and cell cycle patterns were assessed with flow cytometry. The animal model was developed by injecting HCC cells into the dorsum of nude mice. Ad-p53 was injected intratumorally. The animals were killed, and then excised tumors were weighed and analyzed for p53 and p21 protein expression using western blot assay. RESULTS: The introduction of exogenous wild-type p53 resulted in the inhibition of cell growth, high G2/M ratio and cell apoptosis, and low S ratio in PLC/PRF/5. The expression of both p53 and p21 proteins was upregulated in the cells. CONCLUSIONS: Replication-deficient adenoviral vector expressing WT-p53 may be useful for gene therapy of HCC.

Adenoviridae↗

[Aluminum toxicity and tolerance in wheat].

The physiological and biochemical effects of different species of aluminum on the wheat Al-tolerant TAM202 and Al-sensitive TAM105 were investigated. The results showed that mononuclear Al could be absorbed by both of the two strains. Compared with TAM105, however, TAM202 absorbed less aluminum. The pH of the nutrient solution rose with the hydroponics of the two-cultivars. The content of proline in leaves of TAM105 increased obviously. The contents of protein, hexose and uronic acid in cell wall of TAM202 were higher than that in TAM105 under 75 mumol.L-1 Al. The results indicated that Al can activated the synthesis of some components relative to Al-tolerance in cell wall.

Aluminum↗

[Treatment of dying wastewater from a woolen mill with a pilot-scale anaerobic/oxic membrane bioreactor (A/O MBR)].

A pilot-scale (10 t/d) anaerobic/oxic membrane bioreactor (A/O MBR) was used for treatment of dying wastewater from a woolen mill. The results showed that when COD, BOD5 and color in the influent was 179-358 mg/L, 44.8-206 mg/L and 50-240 dilution times (DT), the average COD, BOD5 and color of A/O MBR effluent was 20.2 mg/L, 1.6 mg/L, 25 DT respectively. The removal of COD, BOD5, color, turbidity was 92.1%, 98.4%, 60.7% and 98.9% respectively. Each quota of the treated water met the gray water standards (CJ25.1-89). The A/O MBR process has many advantages, such as stable performance, simple operation, easy management etc. The result of this work could be reference for the designing of industrial scale A/O MBR process for treatment of the woolen mill wastewater.

Anaerobiosis↗

Aortic root replacement.

OBJECTIVE: To report our operative experience with aortic root replacement in 231 patients with aortic root aneurysm and discuss the current indications, methods, and surgical techniques. METHODS: Between January 1994 and August 1999, a group of 231 consecutive patients underwent aortic root replacement at our hospital, with 13 being treated on an emergency basis. There were 189 men and 42 women, ranging in age from 14 to 69 years. The diameter of the aneurysm varied from 4.5 to 11 cm. Among this group, 145 had isolated aortic root aneurysms, 65 suffered from DeBakey type I aortic dissection, and the remaining 21 were diagnosed as having DeBakey type II aortic dissection. Aortic valve regurgitation occurred in all cases. Aortic root replacement was performed with composite valved graft in 229 patients, and in 2 patients the aortic valve was preserved. RESULTS: The hospital mortality rate was 3.03% (7 patients). Early complications included re-exploration for bleeding in 6 patients, pericardial effusion in 9, as well as cerebral infarction, pleural effusion, and pneumothorax in 2 patients each. One hundred and seventy-five patients (78.12%) were followed up, with a mean follow-up time of 15.7 +/- 13.1 months (range, 2 weeks to 65 months). One patient died from lower-limb embolism and renal dysfunction 3 months postoperatively. Three patients died from postoperative anticoagulation accidents. The preoperative and postoperative mean left ventricular end-diastolic diameters were significantly different (68.1 +/- 9.4 mm, range 54 to 112 mm; vs 54.8 +/- 8.2 mm, range 38 to 88 mm; P < 0.001). CONCLUSIONS: Once a diagnosis of acute aortic root dissecting aneurysm is made, the patient should undergo surgery as soon as possible if the general conditions permit. Aortic aneurysm without dissection or with chronic dissection should be operated if the diameter of the aneurysm is greater than 5 cm.

Adolescent↗

Myocardial protection of immature rabbits with an ATP-sensitive K+ channel opener pinacidil.

OBJECTIVE: To investigate the effectiveness of pinacidil, an opener of ATP-sensitive K+ channels, in protecting the myocardium of immature rabbit hearts from ischemic reperfusion injury. METHODS: Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 min of reperfusion on the modified Langendorff apparatus. Fifty-two isolated hearts of 3-4 week-old immature rabbits were divided into 4 groups randomly. During ischemia, 3 different cardioplegic solutions were administered intermittently by infusion every 15 min (20-25 ml each time in all groups). Group 1: control group (n = 13); group 2: Krebs-Henseleit (K-H) solution with potassium (16 mmol/L) (n = 13); group 3: K-H solution with potassium (16 mmol/L) and pinacidil (50 mumol/L) (n = 13); group 4: K-H solution with potassium (16 mmol/L), pinacidil (50 mumol/L) and glibenclamide (10 mumol/L) (n = 13). The pre-ischemic and post-ischemic myocardial functions were assessed by the percentage recovery of the left ventricular developed pressure (LVDP); the left ventricular end-diastolic pressure (LVEDP); both the positive peak and negative peaks of the first derivative of the left ventricular pressures (+/- dp/dtmax); coronary flow; the level of creatine kinase (CK), lactic dehydrogenase (LDH) and aspartate transcarbamoylase (AST) in coronary sinus venous effluent; and by myocardial ultrastructural changes. RESULTS: Before myocardial ischemia, there were no significant differences among the four groups in any of the parameters mentioned above. Post-ischemic recovery of LVDP, LVEDP, +/- dp/dtmax, coronary flow, the level of CK, LDH and AST, and myocardial ultrastructural changes were better in group 3 than those in the three other groups. CONCLUSIONS: As a new and effective composition, pinacidil can significantly improve myocardial protection from cardioplegia for immature rabbit hearts.

Animals↗

[Studies on hereditary deficiency of coagulation factor V].

OBJECTIVE: To explore the mechanisms of hereditary deficiency of coagulation factor V (FV). METHODS: The amount of FV in plasma and platelets was assayed by immunological and biochemical method, FV gene analysis by PCR product sequencing and restriction enzyme analysing, and the biostructural pathology of the identified mutation by molecular modeling. RESULTS: No detectable FV fragments and FV activity were found in the plasma and platelets from the proband of the affected family. His gene analysis revealed a 1763A-->C substitution in a FV allele gene. The mutation might cause the loss of the hydrogen bond between conservative Tyr530 and Glu330, and form a cavity in the protein core. CONCLUSION: The 1763A-->C mutation might cause the instability of FV and be the important mechanism for the hereditary deficiency of FV.

Adult↗

[Orthotopic liver transplantation: report of 70 cases].

OBJECTIVES: To summarize the results of liver transplantation for various end-stage liver diseases at Sun Yat-sen University of Medical Sciences, define the role of liver transplantation in treatment of hepatocellular carcinoma (HCC) and fulminant hepatitis B, and assess the value of lamivudine for preventing HBV recurrence. METHODS: Clinical data of seventy patients undergoing orthotopic liver transplantation (OLT) at Sun Yat-sen University of Medical Sciences between April 1993 and December 2000 were retrospectively analyzed. The main indications for liver transplantation were HCC (26 cases), liver cirrhosis (21), fulminant hepatitis B (12), sclerosing cholangitis (4) and other terminal liver diseases (7). Lamivudine was used in 12 patients with fulminant hepatitis B. Logistic multivariate regression analysis was employed to determine the risk factors predicting outcome of liver transplantation. RESULTS: Fifty-four patients survived for more than one month and 16 patients died within 30 days after OLT. The overall hospital survival rate was 77.1%. The hospital survival rates in Child's A and B patients were 87.5% and 83.3%, respectively. They were superior to those of the Child's C patients (P < 0.05). The outcome of patients with small HCC was superior to that of patients with large HCC. Preoperative APACE III scores, the severity of ascites, and serum creatine level had an independent influence on outcome. Of the patients with fulminant HBV infection, 9 survived for 2-24 months. Treatment with lamivudine monotherapy was both well tolerated and efficacious in patients with fulminant Hepatitis B. CONCLUSIONS: OLT can cure some patients and provide palliation for others with HCC. Patient selection is extremely important for predicting outcome. The results support the application of liver transplantation as a therapeutic modality for various end-stage liver diseases. Lamivudine is effective and safe in OLT for patients with HBV infection.

Adolescent↗

[Clinicopathological and molecular genetic analysis in Chinese typical hereditary nonpolyposis colorectal cancer pedigrees].

OBJECTIVE: To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. METHODS: Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues from 4 probands showed high level of microsatellite instability at more than 2 loci(RER + phenotype). Three of 4 cases lost hMSH2 protein expression and one case showed no hMLH1 protein expression. Three pathological germline mutations (2 on hMSH2 and 1 on hMLH1) were identified. CONCLUSIONS: Chinese typical HNPCC kindreds showed relatively frequent germline mutations of mismatch repair genes. Microsatellite instability analysis and immunohistochemistry staining might be the effective screening methods before direct DNA sequencing for the detection of mismatch repair genes. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC kindreds.

Adult↗