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Biomedical subjects

Jing Liu

Publications and source records attributed to Jing Liu.

At least 235 records · Page 13Linked to original sources

Expression of hepatitis C virus envelope protein 2 induces apoptosis in cultured mammalian cells.

AIM: To explore the role of hepatitis C virus (HCV) envelope protein 2 (E2) in the induction of apoptosis. METHODS: A carboxyterminal truncated E2 (E2-661) was transiently expressed in several cultured mammalian cell lines or stably expressed in Chinese hamster ovary (CHO) cell line. Cell proliferation was assessed by 3H thymidine uptake. Apoptosis was examined by Hoechst 33258 staining, flow cytometry and DNA fragmentation analysis. RESULTS: Reduced proliferation was readily observed in the E2-661 expressing cells. These cells manifested the typical features of apoptosis, including cell shrinkage, chromatin condensation and hypodiploid genomic DNA content. Similar apoptotic cell death was observed in an E2-661 stably expressing cell line. CONCLUSION: HCV E2 can induce apoptosis in cultured mammalian cells.

Animals↗

Mercury and trace element distribution in organic tissues and regional brain of fetal rat after in utero and weaning exposure to low dose of inorganic mercury.

Since it is still absent data about the toxic risk of low dose, especially an environmentally relevant dose of mercury to fetus after their prenatal exposure, this present work was designed to investigate the metabolism of Hg and its effect on the levels of essential trace elements in the organic tissues and the brain regions of infant rats after their exposure to environmentally relevant low dose of Hg(II) during the whole pregnant and weaning period. The pregnant female rats were exposed to a very low dose of 0.2 microg Hg2+/ml (as HgCl2, 12 rats/group) in drinking water from prenatal day 0 continued to postnatal day 20. The contents of Hg and other elements (Cu, K, Mg, Mn, Na, Ca, Co, Fe, Se and Zn) in the liver, kidney, heart, spleen, pancreas and the brain regions (cerebrum, cerebellum, brain stem, hippocampus, thalamus and the remains) of the maternal and their infant rats were determined. The highest Hg contents were found in kidney of both maternal and infant rats. Considering the percentage of Hg accumulation, approximately 52.7%, 38.7%, and 1.66% were found in kidney, liver and brain for maternal rats, respectively, while 23.7%, 48.9% and 15.6% for infant rats. The important findings in this work were that the low dose of inorganic mercury appeared to accumulate in the brain of offspring and more Hg was present in infant brain than in their mother. As in the brain regions, the highest Hg content was present in infant hippocampus and cerebellum, whereas the Hg contents in maternal brains varied not so much. The imbalances of Fe/Cu, Cu/Zn, Zn/Se mass ratios and the molar ratios of Hg over other elements in the Hg-exposed rats were observed.

Administration, Oral↗

A candidate DNA vaccine elicits HCV specific humoral and cellular immune responses.

AIM: To investigate the immunogenicity of candidate DNA vaccine against hepatitis C virus (HCV) delivered by two plasmids expressing HCV envelope protein 1 (E1) and envelope protein 2 (E2) antigens respectively and to study the effect of CpG adjuvant on this candidate vaccine. METHODS: Recombinant plasmids expressing HCV E1 and E2 antigens respectively were used to simultaneously inoculate mice with or without CpG adjuvant. Antisera were then collected and titers of anti-HCV antibodies were analyzed by ELISA. One month after the last injection, animals were sacrificed to prepare single-cell suspension of splenocytes. These cells were subjected to HCV antigen specific proliferation assays and cytokine secretion assays to evaluate the cellular immune responses of the vaccinated animals. RESULTS: Antibody responses to HCV E1 and E2 antigens were detected in vaccinated animals. Animals receiving CpG adjuvant had slightly lower titers of anti-HCV antibodies in the sera, while the splenocytes from these animals showed higher HCV-antigen specific proliferation. Analysis of cytokine secretion from the splenocytes was consistent with the above results. While no antigen-specific IL-4 secretion was detected for all vaccinated animals, HCV antigen-specific INF-gamma secretion was detected for the splenocytes of vaccinated animals. CpG adjuvant enhanced the secretion of INF-gamma but did not change the profile of IL-4 secretion. CONCLUSION: Vaccination of mice with plasmids encoding HCV E1 and E2 antigens induces humoral and cellular immune responses. CpG adjuvant significantly enhances the cellular immune response.

Adjuvants, Immunologic↗

Explaining the increase in coronary heart disease mortality in Beijing between 1984 and 1999.

BACKGROUND: Coronary heart disease (CHD) mortality is rising in many developing countries. We examined how much of the increase in CHD mortality in Beijing, China, between 1984 and 1999 could be attributed to changes in major cardiovascular risk factors and assessed the impact of medical and surgical treatments. METHODS AND RESULTS: A validated, cell-based mortality model synthesized data on (1) patient numbers, (2) uptake of specific medical and surgical treatments, (3) treatment effectiveness, and (4) population trends in major cardiovascular risk factors (smoking, total cholesterol, blood pressure, obesity, and diabetes). Main data sources were the WHO MONICA and Sino-MONICA studies, the Chinese Multi-provincial Cohort Study, routine hospital statistics, and published meta-analyses. Age-adjusted CHD mortality rates increased by approximately 50% in men and 27% in women (1608 more deaths in 1999 than expected by application of 1984 rates). Most of this increase ( approximately 77%, or 1397 additional deaths) was attributable to substantial rises in total cholesterol levels (more than 1 mmol/L), plus increases in diabetes and obesity. Blood pressure decreased slightly, whereas smoking prevalence increased in men but decreased substantially in women. In 1999, medical and surgical treatments in patients together prevented or postponed approximately 642 deaths, mainly from initial treatments for acute myocardial infarction ( approximately 41%), hypertension (24%), angina (15%), secondary prevention (11%), and heart failure (10%). Multiway sensitivity analyses did not greatly influence the results. CONCLUSIONS: Much of the dramatic CHD mortality increases in Beijing can be explained by rises in total cholesterol, reflecting an increasingly "Western" diet. Without cardiological treatments, increases would have been even greater.

Adult↗

Monitoring and control of an anaerobic upflow fixed-bed reactor for high-loading-rate operation and rejection of disturbances.

A new control strategy has been introduced for operating anaerobic digestion processes efficiently at high load. The control system includes a cascade controller embedded into a rule-based supervisory system based on extremum-seeking control. Three process parameters, considered to be the most realistic variables for monitoring of the bioprocess, were selected (pH, biogas production rate, and the difference between the actual biogas flow and its setpoint). The control system examines these variables and varies the organic load by manipulating the influent flow. Good control performance was achieved during the start-up, during steady-state running operations, and during rejection of disturbances. The main advantages of this control approach can be attributed to its ability to adjust control parameters automatically, both for high-load operation and for rejection of disturbances. Furthermore, the influent flow can be tuned automatically according to variations in organic matter in the feed without the characteristics of the influent being considered.

Algorithms↗

Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study.

CONTEXT: The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations. OBJECTIVE: To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS). DESIGN, SETTING, AND PARTICIPANTS: The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years. MAIN OUTCOME MEASURES: "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions. RESULTS: The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort. CONCLUSIONS: The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice.

Adult↗

Association between the FOXP2 gene and autistic disorder in Chinese population.

Several genomewide screens indicated that chromosome 7q was linked to autistic disorder. FOXP2, located on 7q31, is a putative transcription factor containing a polyglutamine tract and a forkhead DNA binding domain. It is one member of the forkhead family who are known to be key regulators of embryogenesis. A point mutation at a highly conserved residue within the forkhead domain co-segregated with affected status in the KE family who was a unique three generation pedigree with a severe speech and language disorder and FOXP2 was directly disrupted by a translocation in an individual who had similar deficits as those of the KE family. Several studies have investigated the role of FOXP2 polymorphisms in autism and none of them found positive association. We performed a family-based association study of three single nucleotide polymorphisms (SNPs) of FOXP2 in 181 Chinese Han trios using the analyses of transmission/disequilibrium test (TDT) and haplotype. We found a significant association between autistic disorder and one SNP, as well as with specific haplotypes formed by this SNP with two other SNPs we investigated. Our findings suggest that the FOXP2 gene may be involved in the pathogenesis of autism in Chinese population.

Alleles↗

On-line monitoring of a two-stage anaerobic digestion process using a BOD analyzer.

A computer-controlled biochemical oxygen demand (BOD) analyzer has been developed for fast estimation of biochemical oxygen demand (BODst) automatically with the purpose of on-line monitoring of a process for conversion of biomass under field conditions. The instrument was tested by on-line monitoring of the connecting stream between two stages of a two-stage anaerobic process in laboratory scale. In the first stage, hydrolysis of sugar beet leaves and its conversion into volatile fatty acids and other low molecular weight substrates took place. The effluent from the first reactor was used as a feed stream to the second stage, i.e. an anaerobic contact reactor. The feed stream was sampled intermittently, diluted and analyzed by the BOD analyzer automatically in order to estimate the organic loading rate to the reactor. The results from this study demonstrated that the BOD analyzer could be a stand-alone and promising sensor device for rapid on-line monitoring of easily biodegradable organic substances in biological treatment processes.

Anaerobiosis↗

Immunostaining for thyroid transcription factor-1 on fine-needle aspiration specimens of lung tumors: a comparison of direct smears and cell block preparations.

BACKGROUND: Fine-needle aspiration (FNA) is used commonly for the diagnosis of pulmonary neoplasms. It has been reported that thyroid transcription factor-1 (TTF-1) is a sensitive and specific marker for certain primary lung tumors. To the authors' knowledge, the use of TTF-1 immunostaining on FNA smears has not been documented in the literature. This study was designed to examine the utility of TTF-1 immunostaining on FNA specimens from various types of lung tumors by comparing the expression rates on Papanicolaou (Pap)-stained and Diff-Quik (DQ)-stained smears with the expression rates on cell block (CB) sections. METHODS: Forty-three FNA specimens of lung tumors were studied, including 34 primary tumors (14 adenocarcinomas, 12 squamous carcinomas, and 8 small cell carcinomas) and 9 metastatic tumors. One Pap-stained slide and one DQ-stained slide were selected from each tumor. The cytologic material from the slides was transferred to positively charged slides. Unstained recuts were obtained from the CB sections. All slides were stained with TTF-1 monoclonal antibody using heat-induced epitope retrieval and a labeled polymer detection system. RESULTS: Twelve of 14 pulmonary adenocarcinomas were positive for TTF-1 (11 specimens on both CB sections and Pap-stained smears and 1 specimen on all 3 preparations, including the DQ-stained smear). Two of 14 adenocarcinomas were negative for TTF-1. Of 12 pulmonary squamous carcinomas, only 1 was positive for TTF-1 (on the CB section and the Pap-stained smear); the others were negative in all 3 preparations. Of eight small cell lung carcinomas, six specimens showed positive staining for TTF-1 on both CB and Pap-stained preparations; one of those also was positive on the DQ-stained smear. The remaining two small cell lung carcinomas were negative for TTF-1 in all three preparations. All metastatic tumors were negative for TTF-1. CONCLUSIONS: TTF-1 immunostaining of pulmonary neoplasms was applicable to FNA smears that were stained previously with the Pap technique, and the rate of positive staining in each tumor type was identical to the rate of positive staining in CB sections and was comparable to that reported in previous publications. Smears previously stained with the DQ method were unreliable for TTF-1 immunostaining.

Adult↗

Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats.

The acute interactive toxicity following exposure to two common organophosphorus (OP) insecticides, chlorpyrifos (CPF) and methyl parathion (MPS), was investigated in adult male rats. Oral LD1 values were estimated by dose-response studies (CPF = 80 mg/kg; MPS = 4 mg/kg, in peanut oil, 1 ml/kg). Rats were treated with both toxicants (0.5 or 1 x LD1) either concurrently or sequentially, with 4-h intervals between dosing. Functional signs of toxicity (1-96 h) and cumulative lethality (96 h) were recorded. Rats treated with CPF (1 x LD1) did not show any signs of toxicity although MPS (1 x LD1) elicited slight to moderate signs (involuntary movements) within 1-2 h. Concurrent exposure (LD1 dosages of both CPF and MPS) caused slight signs of toxicity only apparent between 24 and 48 h after dosing. When rats were treated sequentially with MPS first followed by CPF 4 h later, slight signs of toxicity were noted between 6 and 24 h, whereas reversing the sequence resulted in 100% lethality within 1 h of the second dosage. Following exposure to lower dosages (0.5 x LD1), the CPF first group showed higher signs of cholinergic toxicity compared with MPS first or concurrent groups. Cholinesterase inhibition in plasma, diaphragm, and frontal cortex was generally higher in rats treated sequentially with CPF first than in those treated initially with MPS from 4 to 24 h after dosing. Plasma and liver carboxylesterase inhibition at 4 h was also significantly higher in the CPF first (62-90%) compared with MPS first (22-43%) group, while at 8 and 24 h, there was no significant difference between any of the treatment groups. ChE inhibition assays to evaluate in vitro hepatic detoxification of oxons indicated that carboxylesterase (CE)- and A-esterase-mediated pathways are markedly less important for methyl paraoxon (MPO) than chlorpyrifos oxon (CPO) detoxification. CPF pretreatment blocked hepatic detoxification of methyl paraoxon while MPS pretreatment had minimal effect on hepatic CPO detoxification ex vivo. These findings suggest that the sequence of exposure to two insecticides that elicit toxicity through a common mechanism can markedly influence the cumulative action at the target site (acetylcholinesterase, AChE) and consequent functional toxicity.

Acetylcholinesterase↗

Effects of heat shock protein 70 activation by metabolic inhibition preconditioning or kappa-opioid receptor stimulation on Ca2+ homeostasis in rat ventricular myocytes subjected to ischemic insults.

Heat shock protein 70 (HSP70) mediates delayed cardioprotection of preconditioning. Cytosolic calcium ([Ca(2+)])(i) overload precipitates injury, whereas attenuation of [Ca(2+)](i) overload is believed to be responsible for cardioprotection. There is evidence suggesting a link between HSP70 and [Ca(2+)](i) homeostasis. We hypothesize that activation of HSP70 by preconditioning may restore [Ca(2+)](i) homeostasis altered by ischemic insults. To test the hypothesis, we determined the effects of preconditioning with metabolic inhibition or pretreating with U50,488H [trans-(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide (a kappa-opioid receptor agonist)] on viability and injury, HSP70 expression, and [Ca(2+)](i) in ventricular myocytes subjected to metabolic inhibition and anoxia (MI/A), with blockade of HSP70 synthesis. In myocytes with vehicle pretreatment, the percentage of dead cells determined by trypan blue exclusion, the injury reflected by release of lactate dehydrogenase, and the resting [Ca(2+)](i) measured by spectrofluorometry significantly increased, whereas the amplitude of electrically induced [Ca(2+)](i) transient decreased, after 10 min with 10 mM 2-deoxy-d-glucose and 10 mM sodium dithionite, known to cause MI/A. However, when myocytes were subjected for 30 min to either 20 mM lactate and 10 mM 2-deoxy-d-glucose (MIP) or 30 microM U50,488H (UP) 20 h before MI/A, the changes in viability and injury, and [Ca(2+)](i) responses were significantly attenuated. These were accompanied by a significantly increased HSP70 expression. Furthermore, blockade of HSP70 synthesis with selective antisense oligonucleotides abolished the beneficial effects of MIP or UP. This study provides first evidence that activation of HSP70 induced by preconditioning, which conferred delayed cardioprotection, restored partially the [Ca(2+)](i) homeostasis altered by ischemic insults.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Using electrical impedance detection to evaluate the viability of biomaterials subject to freezing or thermal injury.

This paper is aimed at comprehensively investigating the dynamic low-frequency electrical impedance (DLFI) of biological materials during the processes of freezing, thawing and heating, and combinations of them. Electrical impedance detection (EID) was proposed as a means of rapidly evaluating the viability of biological materials subject to freezing or thermal injury (processes expected to be significant in the practices of cryobiology and hyperthermia). Using two experimental setups, the DLFI for selected biological materials (fresh pork and fish) under various freezing and heating conditions was systematically measured and analyzed. Preliminary results demonstrate that damage that occurs to a biological material due to freezing or heating could result in a significant deviation in its electric impedance value from that of undamaged biomaterials. Monitoring impedance change ratios under various freezing and heating conditions may offer an alternative strategy for assessing the amount of damage sustained by biomaterials subject to cryosurgery, cryo-preservation and hyperthermia. Implementation of the present method in order to develop a new micro-analysis or biochip system is also suggested.

Animals↗

Association between the interleukin-1beta C(-511)T polymorphism and blood pressure in a Chinese hypertensive population.

The interleukin-1beta (IL-1beta) is an important pro-inflammatory cytokine in a broad spectrum of physiological processes. Previous investigations have observed that levels of the IL-1beta were higher in essential hypertensive patients and the IL-1beta gene polymorphism has been shown to be related to IL-1 production. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to hypertension. In this report, we utilized a family-based design to test the association between the IL-1beta C(-511)T polymorphism and blood pressure levels in hypertensive patients chosen from rural communities in Anhui, China. In men, carriers of the IL-1beta (-511)*C allele were found to have lower systolic (P = 0.049) blood pressure levels compared with T homozygotes, which conforms to an additive effect model. By contrast, no significant association between the IL-1beta gene and blood pressure levels was revealed in women. Our results suggested a significant role of the IL-1beta C(-511)T polymorphism in the control of blood pressure in Chinese hypertensives.

Asian People↗

JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD.

JNK has been suggested to be proapoptotic, antiapoptotic, or have no role in apoptosis depending on the cell type and stimulus used. The precise mechanism of JNK action, under conditions when it promotes cell survival, is not entirely clear. Here, we report that JNK is required for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD. IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a constitutively active JNK. JNK phosphorylates BAD at threonine 201, thereby inhibiting BAD association with the antiapoptotic molecule BCL-X(L). IL-3 induces BAD phosphorylation at threonine 201, and replacement of threonine 201 by alanine generates a BAD mutant, which promotes IL-3 withdrawal-induced apoptosis. Thus, our results provide a molecular mechanism by which JNK contributes to cell survival.

Alanine↗

A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent.

Telomerase is a therapeutic target for cancer. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionaly upregulated exclusively in about 90% of cancer cells. Previous studies have demonstrated that hTERT promoter can control the expression of exogenous genes to the telomerase-positive cancer cells, thus hTERT promoter is an excellent candidate for generating cancer-specific oncolytic adenovirus. In this study, we devised a novel oncolytic adenovirus (Ad.TERT) by replacing the normal E1A regulatory elements with hTERT promoter. Ad.TERT displays cancer-specific E1A expression, virus replication and cytolysis in in vitro experiments. In animal experiments, intratumoral administration of Ad.TERT demonstrates potent antitumoral efficacy at least in two xenograft models (Bcap37 and BEL7404). Ad.TERT was targeted by the telomerase activity in cancer cells and has potent antitumoral efficacy in vivo, and since telomerase activity is a wide-ranged tumor marker, Ad.TERT could be a powerful therapeutic agent for a variety of cancers.

Adenoviridae↗

Antimicrobial drug discovery through bacteriophage genomics.

Over evolutionary time bacteriophages have developed unique proteins that arrest critical cellular processes to commit bacterial host metabolism to phage reproduction. Here, we apply this concept of phage-mediated bacterial growth inhibition to antibiotic discovery. We sequenced 26 Staphylococcus aureus phages and identified 31 novel polypeptide families that inhibited growth upon expression in S. aureus. The cellular targets for some of these polypeptides were identified and several were shown to be essential components of the host DNA replication and transcription machineries. The interaction between a prototypic pair, ORF104 of phage 77 and DnaI, the putative helicase loader of S. aureus, was then used to screen for small molecule inhibitors. Several compounds were subsequently found to inhibit both bacterial growth and DNA synthesis. Our results suggest that mimicking the growth-inhibitory effect of phage polypeptides by a chemical compound, coupled with the plethora of phages on earth, will yield new antibiotics to combat infectious diseases.

Anti-Bacterial Agents↗

A systematic study of acupuncture practice: acupoint usage in an outpatient setting in Beijing, China.

Acupuncture textbooks mention a wide assortment of indications for each acupuncture point and, conversely, each disease or indication can be treated by a wide assortment of acupoints. However, little systematic information exists on how acupuncture is actually used in practice: i.e. which points are actually selected and for which conditions. This study prospectively gathered data on acupuncture point usage in two primarily acupuncture hospital clinics in Beijing, China. Of the more than 150 unique acupoints, the 30 most commonly used points represented 68% of the total number of acupoints needled at the first clinic, and 63% of points needled at the second clinic. While acupuncturists use a similar set of most prevalent points, such as LI-4 (used in >65% of treatments at both clinic sites), this core of points only partially overlaps. These results support the hypothesis that while the most commonly used points are similar from one acupuncturist to another, each practitioner tends to have certain acupoints, which are favorites as core points or to round out the point prescription. In addition, the results of this study are consistent with the recent development of "manualized" protocols in randomized controlled trials of acupuncture where a fixed set of acupoints are augmented depending on individualized signs and symptoms (TCM patterns).

Acupuncture Points↗