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Biomedical subjects

Wei Zhou

Publications and source records attributed to Wei Zhou.

At least 217 records · Page 12Linked to original sources

Role of NF-kappaB and cytokine in experimental cancer cachexia.

AIM: To assess the putative involvement of NF-kappaB and pro-inflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND) on cachexia. METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing plus saline, (c) tumor-bearing plus IND (0.25 mg x kg(-1)), (d) tumor-bearing plus IND (0.5 mg x kg(-1)), and (e) tumor-bearing plus IND (2 mg x kg(-1)). Colon 26 adenocarcinoma cells of murine were inoculated subcutaneously to induce cachexia. Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNF-alpha and IL-6 and activity of NF-kappaB in the spleen were investigated in all animals. RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P<0.01), and the weight of gastrocnemius was decreased by 28.7 % (P<0.01). No difference was found between groups in food intake (P>0.05). Gastrocnemius weight was increased markedly (P<0.01) after treatment of IND (0.5 mg x kg(-1)), while the non-tumor body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-alpha and IL-6 (P<0.01). The concentration of TNF-alpha (P<0.05) and IL-6 (P<0.01) in tumor-bearing mice was reduced after administration of 0.5 mg x kg(-1) IND for 7 days. But the level of IL-6 was slightly elevated following treatment of IND 2.0 mg x kg(-1). NF-kappaB activation in the spleen was increased in tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (EMSA). NF-kappaB activity was reduced in mice treated with 0.5 mg x kg(-1) of IND, whereas a higher NF-kappaB activity was observed in mice treated with 2.0 mg x kg(-1) of IND. CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-alpha and IL-6 in tumor-bearing animals, which is controlled by NF-kappaB. Low dose of indomethacin alleviates the cachexia, decreases the activation of NF-kappaB and the serum levels of TNF-alpha and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.

Adenocarcinoma↗

Clinical effects of continuous high volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome.

AIM: To investigate the efficiency of continuous high volume hemofiltration (HVHF) in the treatment of severe acute pancreatitis (SAP) complicated with multiple organ dysfunction syndrome (MODS). METHODS: A total of 28 SAP patients with an average of 14.36+/-3.96 APACHE II score were involved. Diagnostic criteria for SAP standardized by the Chinese Medical Association and diagnostic criteria for MODS standardized by American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) were applied for inclusion. HVHF was started 6.0+/-6.1 (1-30) days after onset of the disease and sustained for at least 72 hours, AN69 hemofilter (1.2 m(2)) was changed every 24 hours. The ultrafiltration rate during HVHF was 4 000 ml/h, blood flow rate was 250-300 ml/min, and the substitute fluid was infused with pre-dilution. Low molecular weight heparin was used for anticoagulation. RESULTS: HVHF was well tolerated in all the patients, and lasted for 4.04+/-3.99 (3-24) days. 20 of the patients survived, 6 patients died and 2 of the patients quited for financial reason. The ICU mortality was 21.4 %. Body temperature, heart rate and breath rate decreased significantly after HVHF. APACHE II score was 14.4+/-3.9 before HVHF, and 9.9+/-4.3 after HVHF, which decreased significantly (P<0.01). Partial pressure of oxygen in arterial blood before HVHF was 68.5+/-19.5 mmHg, and increased significantly after HVHF, which was 91.9+/-25 mmHg (P<0.01). During HVHF the hemodynamics was stable, and serum potassium, sodium, chlorine, glucose and pH were at normal level. CONCLUSION: HVHF is technically possible in SAP patients complicated with MODS. It does not appear to have detrimental effects and may have beneficial effects. Continuous HVHF, which seldom disturbs the hemodynamics and causes few side-effects, is expected to become a beneficial adjunct therapy for SAP complicated with MODS.

APACHE↗

Risk factors of military training-related injuries in recruits of Chinese People's Armed Police Forces.

OBJECTIVE: To assess the incidence, types and risk factors of military training-related injuries in recruits of Chinese People's Armed Police Forces (CPAPF). METHODS: A cohort study was made on the risk factors of injuries in 805 male recruits during the military training from December 25, 1999 to December 25, 2000. RESULTS: A total of 111 recruits (14%) experienced one or more injuries, and the cumulative incidence was 16.1 injuries per 100 soldiers in a year. And 77.7% of the injuries belonged to overuse injuries of the skeletal and muscular systems, the most common type of which was stress fractures. Most injuries occurred in the 3rd month of training. Univariate analysis and logistic regression analysis of possible risk factors for overuse injuries were carried out, and a number of risk factors were identified: history of agricultural labor, history of lower limb injury, flatfoot and less running exercise before entry into the army. But a suitable body mass index (BMI) was a protective factor. Examination of age, body height, smoking, body flexibility and frequency of 2-mile running revealed no significant association with the injuries. CONCLUSIONS: History of agricultural labor, history of lower limb injury, flatfoot, less running exercise before entry into the army and lower BMI were risk factors of the overuse injuries. In order to decrease the incidence of overuse injuries, the young people with good physical ability and shapely body type should be selected during conscription. During the training, nutrition should be improved so as to decrease the incidence of injuries.

Adolescent↗

Study of direct lung injury by seawater in canine models.

OBJECTIVE: To study the mechanism of direct lung injury by seawater and explore its possible management. METHODS: To exclude the interference of hypoxia and acidosis during the study of seawater-induced direct lung injury, 18 normal hybrid dogs were randomly assigned into group A (with all lung lobes perfused with seawater), group R (with the right lung lobe perfused with seawater) and group D (with the diaphragmatic lobe of lung perfused with seawater), with 6 dogs in each group. The changes in blood gas dynamics, blood gas acid-base status and electrolytes, along with the histological changes in the lung tissues were comparatively analyzed between the 3 groups. Bronchial microscope was employed to observe the continuous changes in the bronchioles before and after seawater perfusion in group D, and the concentration of the bronchoalveolar fluid and blood LDH-L and ALP levels were tested. RESULTS: The values of PaO(2), PaCO(2), pH, actual bicarbonate (AB), base excess (BE), tidal volume, and respiration rate in groups A and R were significantly different from those in group D (P < 0.01), and in groups A and R, the above measurements at every stage after seawater perfusion were significantly different from those before perfusion (P < 0.01). In group D, however, blood gas dynamics, blood gas acid-base status and electrolytes changed little after seawater perfusion (P > 0.05). In all the groups, obvious lung tissue injuries were observed under optical microscope after seawater perfusion. Observation with electron microscope revealed injuries to type II alveolar epithelial cells, broadened respiratory mucosa, and platelet adherence. Bronchial microscope in group D presented the bronchus filled with bronchoalveolar fluid, and blood LDH-L and ALP levels kept rising significantly (P < 0.01). Within 4 h after seawater perfusion, no pathological changes were seen in the lung tissues without direct contact with seawater. CONCLUSIONS: Seawater inspiration and retention in the lungs may lead to severe direct lung injury, and is the primary factor responsible for acute lung injury after drowning in the sea.

Animals↗

[An experimental study of apoptosis in epithelia of oral leukoplakia].

OBJECTIVE: The purpose of this study was to investigate the relationship between apoptosis and proliferation of oral mucosa in lesions of leukoplakia and the role of apoptosis in the pathogenesis of this common oral disease. METHODS: The mucosa was obtained from the leukoplakia lesions from 6 patients, with average age of 57 years, and all the patients had not received any treatment before this investigation. The lesions were located on the lip (1), gingiva (1), tongue (2) and buccal mucosa (2). All the patients did not have any systemic diseases. Other three normal oral mucosa tissues were collected as the control. In situ terminal deoxynucleotidyl transferase end-labeling (TUNEL) and avidin-biotin peroxidase complex (ABC) immunohistochemical assay were used to detect single-strand DNA breaks and proliferating cell nuclear antigens (PCNA). The negative control slides were treated with the tris saline buffer to substitute the terminal deoxynucleotidyl transferase (TdT) and PCNA-Ab in the assay. Five consecutive high power fields with the magnification of 400 were used to search for positive stained keratinocytes. RESULTS: Compared with the normal mucosa, the keratinocytes in leukoplakia showed positive apoptotic signals in the nucleus of suprabasal epithelial layers, while PCNA-positive stain was present in the basal position. In the connective tissue, positive apoptotic signals were found in lymphocytes and the endothelia of blood vessels. CONCLUSION: The results indicate that the death of cells in leukoplakia is partly due to apoptosis which may play an important role in the genesis of oral leukoplakia.

Aged↗

Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.

XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (>/=55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk.

Adult↗

[Cloning and polymorphism analysis of prtH gene from Porphyromonas gingivalis].

OBJECTIVE: To clone the prtH gene from Porphyromonas gingivalis (P.g) ATCC 33277 and analyze the polymorphism of prtH gene from 5 strains of P.g in order to explore the relationship between P.g and periodontitis. METHODS: Using PCR, the prtH was amplified and cloned into pGEM-T vector. To illustrate the prtH polymorphism among P.g strains, the genomic DNAs were extracted and screened by PCR with three pairs of specific primers, dot blot and Southern blot hybridization using the biotin-labeled prtH sequence as probe. RESULTS: Recombinant DNA pGEM-T- prtH was verified by restriction endonuclease and sequence assay. Strain W 381 and ATCC 33277 showed the identical results in PCR and hybridization assays, whereas strain ATCC 49417 and 14-3-2 revealed individual hybridization patterns. Strain 47A-1 seemed even not to contain prtH gene. CONCLUSIONS: Different prtH gene sequences exist in different P.g strains. This polymorphism may indicate various potential virulent effects during the infection and pathogenesis. Established PCR protocol is sensitive for identification of prtH gene.

Bacterial Proteins↗

Alterations in molecular pathways of diffusely infiltrating glial neoplasms: application to tumor classification and anti-tumor therapy (Review).

Recent advances in our understanding of the molecular genetic mechanisms underlying diffusely infiltrating brain neoplasms have important implications for the classification and therapy of these tumors. Traditionally, primary brain tumors have been classified histologically; however, it is now clear that tumors within a single histologically defined category are heterogeneous from a molecular genetic perspective. Furthermore, many new experimental therapeutic strategies directed against these almost invariably fatal tumors are aimed at molecular rather than histologic abnormalities. Consequently, the classification of these tumors is in the process of being re-evaluated as underlying molecular genetic mechanisms continue to be elucidated. This review covers traditional histologic based classification of infiltrating glial neoplasms together with molecular abnormalities of these tumors involving p53, epidermal growth factor receptor, the retinoblastoma pathway, platelet derived growth factor receptor, genetic losses on chromosome 10, and loss of heterozygosity on chromosomes 1p and 19q. The contribution of these molecular genetic abnormalities to the classification and therapy of these tumors is discussed. Although at the present no molecular system for the classification of brain tumors has been generally accepted, microarray technologies offer the exciting prospect of practical molecular classification in the future.

Antineoplastic Agents↗

[The compare disquisition of the collateral ligaments: normal and pathologic appearances on MRI].

OBJECTIVE: To evaluate the MR findings of normal and abnormal collateral ligament and the meaning of medical jurisprudence appraisal. METHODS: The MR findings of 12 normal and 13 surgically confirmed injured collateral ligaments were retrospectively reviewed and compared. RESULTS: The normal tibial and fibular collateral ligaments were hypointense string on both T1 and T2 coronal MR images, with average length of 6.8 cm for tibial collateral ligament and 5.7 cm for fibular collateral ligament.13 collateral ligaments were injured, including 6 tibial and 3 fibular collateral ligaments. Two cases(4 ligaments) had both tibial and fibularcollateral ligaments injuries. The injury of collateral ligament was classified as: Grade I(5 ligaments), Grade II(5 ligaments), and Grade III(3 ligaments). The complications of anterior cruciate ligament sprains(3 cases), posterior cruciate ligament sprains(4 cases), meniscal tear(2 cases) were found in 7 patients(63.6%). CONCLUSION: Coronal MR imaging can clearly demonstrate the structure of the knee collateral ligaments, accurately diagnose and classify the ligament injury, and correctly detect the complications, MRI is very valuable for medical jurisprudence appraisal.

Adult↗

Acute lymphangitis treated by moxibustion with garlic in 118 cases.

TCM holds that acute lymphangitis is pathogenically caused by the accumulated internal fire and toxicity, and the external skin injury-induced infection, leading to toxicity going upward along the meridians. The treatment should be given to clear away heat and toxin. Blood letting by a three-edged needle may promote qi and blood circulation and remove the toxic heat. Garlic has the function of antagonizing Staphylococcus aureus, Bacillus dysenteriae and various kinds of bacteria. Since the volatile oil in moxa is antagonistic to bacteria, the burning moxa can also promote the local flow of qi and blood, and enhance the antagonistic effect of garlic on bacteria. Therefore, satisfactory curative results can be achieved by the therapy.

Adolescent↗

[Treatment of acute lung injury due to sea water aspiration in dogs by early massive bronchoalveolar lavage: an experimental study].

OBJECTIVE: To investigate the therapeutic effects of massive bronchoalveolar lavage at early stage of acute lung injury induced by sea water aspiration. METHODS: Twelve mongrel dogs were subjected to sea water infusion of the entire lungs and were subsequently randomized into 2 groups. The dogs in group A received intravenous saline transfusion 24 h after injury, while those in group B underwent bronchoscopic lavage of injured lungs with 450 ml 0.45% saline 15 min after injury. Unassisted breathing was maintained in both groups, and the gas exchange function of the bilateral lungs and the levels of lactate dehydrogenase, alkaline phosphatase in the bronchoalveolar fluid were observed, with the hemodynamics indices monitored continuously. The lungs of the dogs were finally removed for morphological study under both light and electron microscopes, and the water content and wet- to dry-weight ratio of the lung tissues were determined. RESULTS: A total lavage volume of approximately 30 ml/kg x b.w. was used, and the liquid volume remaining in the lungs after operation ranged from 80 to 120 ml. All the dogs manifested significant declination in pulmonary function after the drowning. PaO2 in group B decreased significantly soon after the lavage but then increased gradually to a higher levels than group A. The dogs in group B had smaller lung water content and lower levels of lactate dehydrogenase and alkaline phosphatase in the bronchoalveolar fluid, showing improved oxygenation in comparison with group A. The inflammatory reaction and edema in lungs were also markedly alleviated in group B. CONCLUSION: Treatment with massive lung lavage in early stage after sea water aspiration can effectively protect the lung tissues from damage and alleviate the inflammatory reaction and pulmonary edema, helping to improve the lung function.

Animals↗

Hydroxyethyl starch inhibits NF-kappaB activation and prevents the expression of inflammatory mediators in endotoxic rats.

Hydroxyethyl starch (HES) has been shown to be beneficial in several inflammatory situations, but the mechanisms are unclear. The present study tested the hypothesis that HES has effects on nuclear factor kappa B (NF-kappaB) activation and the expression of inflammatory mediators induced by lipopolysaccharide. Sepsis was induced in male Wistar rats by injection of lipopolysaccharide (LPS, 6 mg/kg, i.p.). At 1 min after the LPS challenge, HES was infused via the right external jugular vein at the following doses: 3.75, 7.5, 15, or 30 ml/kg. NF-kappaB activation in peripheral blood mononuclear cells and neutrophils, plasma concentrations of tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC), expression of CD11b on the blood neutrophil cell surface, and neutrophil sequestration in multiple organs were examined 2 or 4 hr after the LPS challenge. Treatment of rats with HES (3.75 and 7.5 ml/kg) prevented LPS-induced NF-kappaB activation, and inhibited, in a dose-related manner, LPS-induced TNF-alpha and CINC expression. The 4 graded doses of HES decreased CD11b expression in a dose-dependent manner. HES significantly reduced neutrophil sequestration in lung, heart, and liver. These results suggest that HES has an anti-inflammatory effect in endotoxic rats. This effect is mediated by inhibition in the production pathways for inflammatory mediators, including NF-kappaB activation.

Animals↗

[Abnormal interferon-inducible protein-10 expression in the labial glands of patients with Sjogren's syndrome].

OBJECTIVE: To investigate whether interferon-inducible protein 10 (IP-10) is involved in the inflammatory process of the labial gland of patients with Sjogren's Syndrome (SS). METHODS: Forty-nine patients performed labial gland biopsy, the number of lymphocytes in the biopsy tissues was calculated and the IP-10 was detected by the methods as following: 39 biopsied labial tissues were examined by RT-PCR, among them, 21 were from primary SS, 5 from secondary SS and 13 from other diseases. With RT-PCR, the IP-10 and beta-actin were co-amplified with specific primers. The gel-fractioned and ethidium bromide amplification products were then analyzed by densitometry. The expression of IP-10 was semi-quantificated by IP-10/beta-actin ratio. Twenty-one samples were examined by immunohistochemistry with specific goat anti-IP-10 antibody, 10 of them from primary SS, 3 from secondary SS, 8 from other diseases. 11 out of 21 samples were examined by both RT-PCR and immunohistochemistry. RESULTS: The expression of IP-10 mRNA was significantly up-regulated in labial glands of patients with SS compared with other diseases (IP-10/beta-actin ratio was 0.329 +/- 0.157 vs 0.099 +/- 0.059, P < 0.01). The number of lymphocyte infiltration foci in labial glands of patients with SS correlated to the IP-10/beta-actin ratio (r = 0.657, P < 0.05). Ductal epithelial cells and some of the infiltrating lymphocytes were stained by anti-IP-10 antibody by immunohistochemistry in 8 of the primary SS (8/10), all of the secondary SS (3/3) and one with primary biliary sclerosis (1/8). The expression of IP-10 protein detected by immunohistochemistry was consistent with that of mRNA detected by RT-PCR. CONCLUSIONS: IP-10 is abnormally highly expressed in the labial glands of patients with SS and positively relates to the lymphocyte infiltration. It thus suggests chemokine IP-10 may be one of the important molecules attracting the lymphocytes to the minor salivary glands to form the lymphocytic foci of Sjogren's Syndrome.

Adult↗

A novel anti-proliferative property of clusterin in prostate cancer cells.

Clusterin is a ubiquitous secretory glycoprotein that is known to suppress certain forms of apoptosis. Since apoptosis and proliferation are two opposing cellular events, it remains unclear if clusterin has any effect on cellular proliferation. The objective of the present study was to examine the effects of clusterin on proliferation in a prostate cancer cell line, LNCaP. We found that clusterin inhibited EGF-mediated proliferation in these cells, as measured by (3)H-thymidine incorporation and by cell counting. Clusterin did not bind with EGF nor did it block phosphorylation of the EGF receptor. Treatment of LNCaP cells with EGF resulted in a transient increase in the expression of both c-Fos and c-Jun. Addition of clusterin to these cultures significantly down-regulated the protein level of c-Fos, but not c-Jun. These results demonstrated a novel biological role for clusterin. Clusterin is not only anti-apoptotic but also anti-proliferative. The anti-proliferative event maybe associated with a down-regulation of c-Fos.

Cell Division↗

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts.

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Animals↗

Phage display particles expressing tumor-specific antigens induce preventive and therapeutic anti-tumor immunity in murine p815 model.

The efficacy of phage display particles expressing tumor antigen P1A35-43 in inducing protective and therapeutic anti-tumor immune responses were studied. A protective immune response against a lethal progressive P815 mastocytoma tumor cell challenge was established after subcutaneous injection of phage display particles. Furthermore, the vaccine suppressed growth of pre-existing tumors. Immunization with the hybrid phage particles elicited P1A(35-43) specific CTL responses and a Th1-dominated immune response with phage particle-specific secretion of IFN-gamma but not IL-4. Our results indicate that phage display particles might be a useful vaccine form for tumor-associated antigen epitopes in tumor immunotherapy.

Animals↗