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Biomedical subjects

Wei Yang

Publications and source records attributed to Wei Yang.

At least 127 records · Page 7Linked to original sources

Activation of the p38 MAPK pathway by follicle-stimulating hormone regulates steroidogenesis in granulosa cells differentially.

In the present study, we started out to test whether the follicle-stimulating hormone (FSH)-activated p38 MAPK signaling cascade was involved in the regulation of steroidogenesis in granulosa cells (GCs). GCs were prepared from the ovaries of DES-treated immature rats and cultured in serum-free medium. Treatment of GCs with FSH (50 ng/ml) induced the phosphorylation of p38 MAPK rapidly with the phosphorylation being observed within 5 min and reaching the highest level at 30 min. Such activation was protein kinase A-dependent as indicated by the results using specific inhibitors. FSH stimulated the production of progesterone and estradiol as well as the expression of the steroidogenic acute regulatory protein (StAR) in a time-dependent manner, with a maximum level being observed in the production of progesterone and StAR at 48 h. Moreover, the potent p38 MAPK inhibitor SB203580 (20 microM) augmented FSH-induced progesterone and StAR production, while reduced FSH-induced estradiol production at the same time (P<0.01). RT-PCR data showed that inclusion of SB203580 in the media enhanced FSH-stimulated StAR mRNA production, while decreased the FSH-stimulated P450arom mRNA expression (P<0.05). Immunocytochemical studies showed that FSH treatment together with the inhibition of p38 MAPK activity resulted in a higher expression of StAR in mitochondria than FSH treatment alone. FSH also significantly up-regulated the protein level of LRH-1, a member of the orphan receptor family that activates the expression of P450arom in ovaries and testes. p38 MAPK inactivation down-regulated the basal and FSH-induced LRH-1 expression significantly. The intra-cellular level of DAX-1, another orphan receptor that inhibits StAR expression, also decreased upon p38 MAPK being inactivated. For the first time, the present study suggests that FSH-activated p38 MAPK signal pathway regulates progesterone and estrogen production in GCs differentially, and that the transcription factors LRH-1 and DAX-1 might play important roles in the process.

Animals↗

[Discussion on design and quality control of clinical trials of traditional Chinese medicine on the basis of Fuhuang Tablets clinical study].

OBJECTIVES: To assess the efficacy of Fuhuang Tablets in treating internal hemorrhoid hemorrhage and discussing the design and quality control of clinical trials of traditional Chinese medicine. METHODS: According to two-center, randomized, blinded and controlled study, 144 patients with internal hemorrhoids were divided into 2 groups. Seventy-two patients were treated with Fuhuang Tablets (4 tablets t.i.d. per os) and the other 72 patients were treated with Zhining Tablets (4 tablets t.i.d. per os). Symptoms and signs of the patients were recorded and evaluated at the third and seventh day of treatment respectively. RESULTS: At the third day of treatment, the overall response rates of Fuhuang Tablets-treated group and Zhining Tablets-treated group were 58.57% and 27.78% respectively, with statistic difference between the two groups (P<0.05). At the seventh day of treatment, the overall response rates of Fuhuang Tablets-treated group and Zhining Tablets-treated group were 91.43% and 81.94% respectively, with no statistic difference between the two groups. The laboratory test results and life signs of the 144 patients were normal before and after the treatment. CONCLUSION: Fuhuang Tablets are effective and safe in treating internal hemorrhoid hemorrhage.

Adolescent↗

[Quality of life of primary hepatocellular carcinoma patients after radiofrequency ablation].

BACKGROUND & OBJECTIVE: Previously, treatment outcome evaluation of hepatocellular carcinoma (HCC) was focused on cure rate, survival rate, and survival time. The quality of life (QOL) of cancer patients has been emphasized during the past decade, and used to evaluate treatment outcome of cancer and chronic disease. This study aimed to evaluate the QOL of HCC patients treated with radiofrequency ablation (RFA), and compare with that of patients treated with transcatheter arterial chemoembolization (TACE) or TACE in combination with RFA. METHODS: A QOL questionnaire (QOL-LC V2.0) was used on 160 HCC patients, in which 80 patients underwent RFA (RFA group), 40 underwent TACE (TACE group), and 40 underwent TACE in combination with RFA (combination group). The 3 groups were comparable in distributions of age, gender, clinical stage, and so on. RESULTS: The median overall QOL score was higher in RFA group and combination group than in TACE group (168.6 vs. 146.8, P=0.025; 162.8 vs. 146.8, P>0.05). The median QOL score in symptom/side effect domain was significantly higher in RFA group and combination group than in TACE group (45.5 and 46.0 vs. 38.1, P<0.01). The physical score was slightly higher in RFA group and combination group than in TACE group. Spearman's correlation analysis showed that age, income, liver function, tumor recurrence, and complications were related to the QOL of HCC patients after treatment. The degree of liver function damage, complications, and tumor recurrence were significantly higher in TACE group than in RFA group (P<0.05). The 1-, 2-, and 3-year survival rates of RFA group were significantly higher than those of TACE group (92.8% vs. 74.3%, 89.3% vs. 48.2%, and 76.5% vs. 48.2%, P=0.041), but had no significant difference with those of combination group (94.1%, 87.4%, and 60.0%). CONCLUSIONS: RFA is an effective and micro-invasive treatment for liver cancer. Compare with TACE alone, TACE in combination with RFA may decrease liver function damage and improve QOL of HCC patients.

Adult↗

[Effects of 100 Hz vibration on ultrastructure of soleus muscle in tail-suspended rats].

OBJECTIVE: To study the effects of 100 Hz vibration on ultrastructure of intrafusal and extrafusal fibers in soleus muscle of tail-suspended rats. METHOD: Weightlessness was simulated by tail suspension of female rats. The ultrastructure of intrafusal and extrafusal fibers of soleus muscle were examined after exposure to 100 Hz vibration. RESULT: The ultrastructure of intrafusal and extrafusal fibers of soleus muscles showed obvious retrograde changes after 7 d tail suspension, whereas these changes were not obvious after 7 d tail suspension plus 100 Hz vibration. CONCLUSION: High frequency vibration can counteract the effect of simulated weightlessness on ultrastructure of intrafusal and extrafusal fibers in soleus muscles of rats.

Animals↗

[Protective effects of the granule of Sambucus chinensis lindl on acute hepatic injury].

OBJECTIVE: To investigate the protective effects of the granule of Sambucus chinensis Lindl on acute hepatic injury. METHODS: The acute liver-injury model induced by CCl4 or D-GalN or ConA was established in mice or rats. RESULTS: The granule of Sambucus chinensis Lindl showed significantly protective effects on mice acute hepatic injury induced by CCl4 ,and the effects were concern of antagonizing lipoperoxidation and improving energy of Ca2+ -ATPase of theca mitochondria and microsome. It showed significantly protective effects on mice or rats acute hepatic injury induced by D-GalN or Con A, too. CONCLUSION: The granule of Sambucus chinensis Lindl showed significantly protective effects against many kinds of chemical and immunological liver injuries.

Animals↗

The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2.

Dynamic regulation of integrin adhesiveness is required for immune cell-cell interactions and leukocyte migration. Here, we investigate the relationship between cell adhesion and integrin microclustering as measured by fluorescence resonance energy transfer, and macroclustering as measured by high resolution fluorescence microscopy. Stimuli that activate adhesion through leukocyte function-associated molecule-1 (LFA-1) failed to alter clustering of LFA-1 in the absence of ligand. Binding of monomeric intercellular adhesion molecule-1 (ICAM-1) induced profound changes in the conformation of LFA-1 but did not alter clustering, whereas binding of ICAM-1 oligomers induced significant microclustering. Increased diffusivity in the membrane by cytoskeleton-disrupting agents was sufficient to drive adhesion in the absence of affinity modulation and was associated with a greater accumulation of LFA-1 to the zone of adhesion, but redistribution did not precede cell adhesion. Disruption of conformational communication within the extracellular domain of LFA-1 blocked adhesion stimulated by affinity-modulating agents, but not adhesion stimulated by cytoskeleton-disrupting agents. Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands.

Binding, Competitive↗

Structure of the MutL C-terminal domain: a model of intact MutL and its roles in mismatch repair.

MutL assists the mismatch recognition protein MutS to initiate and coordinate mismatch repair in species ranging from bacteria to humans. The MutL N-terminal ATPase domain is highly conserved, but the C-terminal region shares little sequence similarity among MutL homologs. We report here the crystal structure of the Escherichia coli MutL C-terminal dimerization domain and the likelihood of its conservation among MutL homologs. A 100-residue proline-rich linker between the ATPase and dimerization domains, which generates a large central cavity in MutL dimers, tolerates sequence substitutions and deletions of one-third of its length with no functional consequences in vivo or in vitro. Along the surface of the central cavity, residues essential for DNA binding are located in both the N- and C-terminal domains. Each domain of MutL interacts with UvrD helicase and is required for activating the helicase activity. The DNA-binding capacity of MutL is correlated with the level of UvrD activation. A model of how MutL utilizes its ATPase and DNA-binding activities to mediate mismatch-dependent activation of MutH endonuclease and UvrD helicase is proposed.

Adenosine Triphosphatases↗

Proliferating cell nuclear antigen-dependent coordination of the biological functions of human DNA polymerase iota.

Y-family DNA polymerases are believed to facilitate the replicative bypass of damaged DNA in a process commonly referred to as translesion synthesis. With the exception of DNA polymerase eta (poleta), which is defective in humans with the Xeroderma pigmentosum variant (XP-V) phenotype, little is known about the cellular function(s) of the remaining human Y-family DNA polymerases. We report here that an interaction between human DNA polymerase iota (poliota) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of poliota in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of poliota or the interdomain connector loop of PCNA diminish the binding between poliota and PCNA and concomitantly reduce PCNA-dependent stimulation of poliota activity. Furthermore, although retaining its capacity to interact with poleta in vivo, the poliota-PIP box mutant fails to accumulate in replication foci. Thus, PCNA, acting as both a scaffold and a modulator of the different activities involved in replication, appears to recruit and coordinate replicative and translesion DNA synthesis polymerases to ensure genome integrity.

Amino Acid Sequence↗

[A de nono I462S mutation in the KRT6A gene is associated with pachyonychia congenita type I].

OBJECTIVE: To analyze the KRT6A gene mutation and mutating patterns in a sporadic Chinese patient with Pachyonychia congenita (PC)-1 so as to provide a basis for gene diagnosis and genetic counseling of this disorder. METHODS: Genomic DNA was extracted from whole blood by standard methods from a female patient with PC-1 and her parents, and from 50 normal, unrelated individuals. Primers for specific amplification of the structural KRT6A gene without co amplification of homologous genes were designed and synthesized. All exons of the gene and their flanking intronic sequences were amplified using polymerase chain reaction (PCR) and subjected to automatic DNA sequencing. The mutation was confirmed by Mbo I restriction digestion of the KRT6A-specific PCR products. RESULTS: Direct sequencing of the PCR products revealed a novel heterozygous missense mutation, I462S in the KRT6A gene, which resulted from T to G transversion at nucleotide 1385 (1385T > G) in exon 7 was detected in the patient. This mutation would result in the substitution of Isoleucine by Serine at codon 462 (I462S) located in the end 2B domain of keratin 6A. No such mutation was found in the patient's parents by sequencing of PCR products and this mutation was confirmed in the patient and excluded from both parents and 50 normal, unrelated controls by restriction analysis of PCR fragments using Mbo I enzyme. CONCLUSIONS: A de novo missense mutation in the KRT6A gene, I462S, has been found in a sporadic PC-1 patient. The identification of this novel mutation in the KRT6A gene provides further evidence that mutation in the KRT6A gene causes PC-1 phenotype.

Base Sequence↗

High-efficiency, environment-friendly electroluminescent polymers with stable high work function metal as a cathode: green- and yellow-emitting conjugated polyfluorene polyelectrolytes and their neutral precursors.

A series of aminoalkyl-substituted polyfluorene copolymers with benzothiadiazole (BTDZ) of different content were synthesized by Suzuki coupling reaction, and their quaternized ammonium polyelectrolyte derivatives were obtained through a postpolymerization treatment on the terminal amino groups. Copolymers are soluble in environmentally friendlier solvents, such as alcohols. It was found that the efficient energy transfer occurs by exciton trapping on the narrow band gap BTDZ site under UV illumination. Only 1% of BTDZ content is needed to completely quench a fluorene emission for both the neutral and the quaternized copolymers in the neat film. Absolute PL efficiencies of copolymer films were greatly enhanced as a result of the suppression of excimer formation. Light-emitting devices fabricated from these copolymers show high external quantum efficiencies over 3% and 1% for the neutral precursor and the quaternized copolymers, respectively, with high work function metals such as Al as a cathode. To the best of our knowledge, this is the first report on an electroluminescent polymer which bears the high EL efficiency, the electron-injection ability from high work function metals, and the solubility in environment-friendly solvents at the same time. These features make them a promising candidate for the next generation of light-emitting copolymers in PLED flat panel display application.

Journal Article↗

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring.

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk. Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. Dietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline. NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17 (95% confidence interval: 0.04, 0.76). Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.

Betaine↗

[Sigma rectum pouch for urinary diversion].

OBJECTIVE: To investigate the clinical outcome of sigma rectum pouch as a continent form of urinary diversion. METHODS: The clinical data of 38 patients, 32 males and 7 females, aged 53.2 (42 - 68) with muscle-invading bladder carcinoma who underwent a Mainz pouch II procedure after radical cystectomy 1996 - 2001 were analyzed. The intestine was incised over a length of 20 - 24 cm with the junction of sigmoid colon and rectum as the midpoint so as to create a low-pressure reservoir for urine and side-to-side anastomosis was performed on the posterior borders of the rectosigmoid wall. Submucosal tunnel technique was employed in antireflux urethral implantation. The patients were followed up for 7 - 60 months with a mean of 30 months postoperatively. RESULTS: Continence has been achieved in all the 38 patients with a micturition frequency of 3 - 5 times during daytime and 0 - 3 times at night. The mean volume of pouch was 515.6 ml (400 - 650 ml). The basal intra-reservoir pressure was 8 - 23 cm H(2)O (mean 16.5 cm H(2)O, 1 cm H(2)O = 0.098 kPa), the highest peak pressure was 12 - 33 cm H(2)O (mean 21.3 cm H(2)O). CONCLUSION: A modified sigmoid rectal pouch procedure provides a reservoir with a higher capacity and lower pressure without a reflux to the upper urinary tract and descending colon with lower incidence of complication, it is also a better alternative diversion procedure that would be easily accepted by surgeons and patients.

Adult↗

Effect of traditional Chinese medicinal enemas on ulcerative colitis of rats.

AIM: To investigate the effects of traditional Chinese medicinal enema (TCME) on inflammatory and immune response of colonic mucosa of rats with ulcerative colitis (UC), and to observe the pathogenic mechanism. METHODS: Thirty UC rats, induced by intestinal enema together with 2.4-dinitrochlorobenzene (DNCB) and acetic acid, were randomly divided into 3 groups, i.e., GI, GII and GIII. Groups GI and GII were administered with TCME and salazosulfapyridine enema (SASPE), respectively. Group GIII was clystered with only normal saline (NSE), served as control. Group GIV was taken from normal rats as reference, once daily, from the 7th day after the establishment of UC for total 28 d. Interleukin-6 (IL-6) in the colonic mucosa was assayed by (3)H-TdR incorporation assay. Colonic mucosal lymphocyte subpopulation adhesive molecules, CD(4)(+)CD(11a )(+), CD(4)(+)CD(18)(+), CD(8)(+)CD(11a)(+), CD(8)(+)CD1(18)(+) (LSAM), tumor necrosis factor (TNF)-alpha, and interferon-gamma (IFN-gamma), were detected by enzyme linked immunosorbent assay (ELISA). Moreover, the expression of TNF-alpha mRNA and IFN-gamma mRNA in colonic mucosa were detected by polymerase chain reaction (RT-PCR). RESULTS: Before therapies, in model groups, GI, GII and GIII, levels of IL-6, TNF-alpha, IFN-gamma, CD(8)(+)CD(11a)(+) and CD(8)(+)CD(18)(+) were significantly different (38.29+/-2.61 U/mL, 16.54+/-1.23 ng/L, 8.61+/-0.89 ng/L, 13.51+/-2.31% and 12.22+/-1.13%, respectively) compared to those in GIV group (31.56+/-2.47 U/mL, 12.81+/-1.38 ng/L, 5.28+/-0.56 ng/L, 16.68+/-1.41% and 16.79+/-1.11%, respectively). After therapeutic enemas, in GI group, the contents of IL-6 (32.48+/-2.53 U/m), TNF-alpha (13.42+/-1.57 ng/L) and IFN-gamma (5.87+/-0.84 ng/L) were reduced; then, the contents of CD(8)(+)CD(11a)(+) (16.01+/-1.05 %) and CD(8)(+)CD(18)(+) (16.28+/-0.19%) were raised. There was no significant difference between groups GI and GIV, but the difference between groups GI and GII was quite obvious (P<0.05). The expressions of TNF-alpha mRNA and IFN-gamma mRNA in group GIII were much higher than those of group GIV, but those in group GI were significantly suppressed by TCME therapy. CONCLUSION: Ulcerative colitis is related to colonic regional mucosal inflammatory factors and immune imbalance. TCME can effectively inhibit regional mucosal inflammatory factors and improve their disorder of immunity.

Animals↗

The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer.

Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed.

Adaptor Proteins, Signal Transducing↗

Large liver tumors: protocol for radiofrequency ablation and its clinical application in 110 patients--mathematic model, overlapping mode, and electrode placement process.

PURPOSE: To establish a preoperative protocol for ultrasonographically guided percutaneous radiofrequency (RF) ablation of large liver tumors that is based on mathematic models and clinical experience and to evaluate the role of this protocol in RF ablation. MATERIALS AND METHODS: A regular prism and a regular polyhedron model were used to develop a preoperative protocol for liver tumor ablation. This protocol enabled the authors to minimize the number of ablation spheres, optimize the overlapping mode, and determine the electrode placement process. One hundred ten patients with 121 liver tumors were treated by using this protocol. Sixty-nine patients had 74 hepatocellular carcinomas (HCCs), and 41 had 47 metastases to the liver (ie, metastatic liver carcinomas [MLCs]). Patients underwent follow-up helical computed tomography (CT) 1 month and every 2-3 months after RF ablation. Ablation was considered a success if no contrast enhancement was detected in the treated area on the CT scan obtained at 1 month. RESULTS: A total of 536 ablations were performed in the 121 tumors. The ablation success rate was 87.6% (106 of 121 tumors); the local recurrence rate, 24.0% (29 of 121 tumors); and the estimated mean recurrence-free survival, 17.1 months. Twenty-five patients underwent 38 re-treatments for local tumor recurrence. Major complications occurred in seven patients. Of these patients, only one, who had a tumor close to the colon, had a colon perforation 1 week after RF and required surgical intervention. CONCLUSION: The described protocol for treatment of large tumors had a success rate of 87.6% and a local recurrence rate of 24.0%.

Adult↗

Investigating the role of the little finger domain of Y-family DNA polymerases in low fidelity synthesis and translesion replication.

Dpo4 and Dbh are Y-family polymerases that originate from two closely related strains of Sulfolobaceae. Quite surprisingly, however, the two polymerases exhibit different enzymatic properties in vitro. For example, Dpo4 can replicate past a variety of DNA lesions, yet Dbh does so with a much lower efficiency. When replicating undamaged DNA, Dpo4 is prone to make base pair substitutions, whereas Dbh predominantly makes single-base deletions. Overall, the two proteins are 54% identical, but the greatest divergence is found in their respective little finger (LF) domains, which are only 41% identical. To investigate the role of the LF domain in the fidelity and lesion-bypassing abilities of Y-family polymerases, we have generated chimeras of Dpo4 and Dbh in which their LF domains have been interchanged. Interestingly, by replacing the LF domain of Dbh with that of Dpo4, the enzymatic properties of the chimeric enzyme are more Dpo4-like in that the enzyme is more processive, can bypass an abasic site and a thymine-thymine cyclobutane pyrimidine dimer, and predominantly makes base pair substitutions when replicating undamaged DNA. The converse is true for the Dpo4-LF-Dbh chimera, which is more Dbh-like in its processivity and ability to bypass DNA adducts and generate single-base deletion errors. Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member.

Amino Acid Sequence↗