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Biomedical subjects

Yifeng Zhou

Publications and source records attributed to Yifeng Zhou.

At least 19 recordsLinked to original sources

Morphology-tunable and photoresponsive properties in a self-assembled two-component gel system.

Photoresponsive C3-symmetrical trisurea self-assembling building blocks containing three azobenzene groups (LC10 and LC4) at the rim were designed and synthesized. By introducing a trisamide gelator (G18), which can self-aggregate through hydrogen bonds of acylamino moieties to form a fibrous network, the mixture of LC10 (or LC4) and G18 forms an organogel with coral-like supramolecular structure from 1,4-dioxane. The cooperation of hydrogen bonding and the hydrophobic diversity between these components are the main contributions to the specific superstructure. The two-component gel exhibits reversible photoisomerization from trans to cis transition without breakage of the gel state.

Journal Article↗

Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

Adult↗

Treated amblyopes remain deficient in spatial vision: a contrast sensitivity and external noise study.

To evaluate residual spatial vision deficits in treated amblyopia, we recruited five clinically treated amblyopes (mean age=10.6 years). Contrast sensitivity functions (CSF) in both the previously amblyopic eyes (pAE; visual acuity=0.944+/-0.019 MAR) and fellow eyes (pFE; visual acuity=0.936+/-0.021 MAR) were measured using a standard psychophysical procedure for all the subjects. The results indicated that the treated amblyopes remained deficient in spatial vision, especially at high spatial frequencies, although their Snellen visual acuity had become normal in the pAEs. To identify the mechanisms underlying spatial vision deficits of treated amblyopes, threshold vs external noise contrast (TvC) functions--the signal contrast necessary for the subject to maintain a threshold performance level in varying amounts of external noise ("TV snow")--were measured in both eyes of four of the subjects in a sine-wave grating detection task at several spatial frequencies. Two mechanisms of amblyopia were identified: increased internal noise at low to medium spatial frequencies, and both increased internal noise and increased impact of external noise at high spatial frequencies. We suggest that, in addition to visual acuity, other tests of spatial vision (e.g., CSF, TvC) should be used to assess treatment outcomes of amblyopia therapies. Training in intermediate and high spatial frequencies may be necessary to fully recover spatial vision in amblyopia in addition to the occlusion therapy.

Adolescent↗

Chronic morphine exposure impairs short-term synaptic depression of geniculo-cortical visual pathway in vivo.

Chronic morphine exposure can induce addiction and affect synaptic plasticity, but the underlying neuronal mechanisms remain unknown. Two forms of short-term synaptic depression (paired-pulse depression (PPD) and frequency depression) were investigated in vivo in the geniculo-cortical visual pathway of morphine-treated and saline-treated (as control) adult rats. Acute exposure to morphine had no effect on paired-pulse synaptic depression and 10-40 Hz induced frequency synaptic depression. However, chronic morphine exposure reduced markedly the paired-pulse depression and frequency depression at 40 Hz. The effect of chronic morphine exposure on short-term synaptic plasticity in the geniculo-cortical visual pathway was sensitization given that morphine re-exposure further significantly reduced the short-term synaptic depression. Interestingly, the further reduction in short-term synaptic depression due to re-exposure of morphine was recovered to normal (control) levels at 3 to 6h after morphine re-exposure. These findings suggest that chronic morphine treatment could significantly degrade the short-term synaptic plasticity of geniculo-cortical visual pathway.

Action Potentials↗

Functional degradation of visual cortical cells in aged rats.

Functional degradation of mammalian visual cortex is associated with aging. It has been hypothesized that much of the decline might be mediated by a degradation of cortical inhibitory system during senescence. In the present work, we compared the properties of adaptation, onset latency and signal-to-noise ratio in primary visual cortex of young and old rats using extracellular single-unit techniques. The short-term synaptic plasticity of young and old rats was also studied using field potential recording techniques. We found significant increased adaptation, prolonged onset latency, lower signal-to-noise ratio and decreased short-term synaptic plasticity in aged rats. The results are in accordance with previously reported functional declines in old monkeys and old cats, indicating a universal mechanism of degradation in cortical function that accompanies old age in different mammalian species.

Adaptation, Physiological↗

Identify mechanisms of amblyopia in Gabor orientation identification with external noise.

In this study, we applied the external noise method and the PTM model to identify mechanisms underlying performance deficits in amblyopia. Amblyopic and normal observers performed a Gabor orientation identification task in fovea. White external noise was added to the Gabor stimuli. Threshold versus external noise contrast (TvC) functions were measured at two performance criterion levels. For a subset of observers, we also manipulated the center spatial frequency of the Gabor. We found that two independent factors contributed to amblyopic deficits: (1) increased additive internal noise, and (2) deficient perceptual templates. Whereas increased additive noise underlay performance deficits in all spatial frequencies, the degree of perceptual template deterioration increased with the center spatial frequency of the Gabor.

Adult↗

Opioid receptor binding and antinociceptive activity of the analogues of endomorphin-2 and morphiceptin with phenylalanine mimics in the position 3 or 4.

Endomorphin-2 (EM-2) and morphiceptin are the same class of putative mu-opioid receptor ligands. To investigate the effectiveness of phenylglycine (Phg, L or D) and homophenylalanine (Hfe) as the surrogates of phenylalanine in the position 3 and/or 4 of them, a series of their analogues were synthesized. Opioid receptor binding affinities were determined. Two analogues, [Hfe3]EM-2 and [Phg4] (EM-2/morphiceptin), showed different but potent antinociceptive activity in mouse hot-plate test, the results combined with their half-lives of degradation by mouse brain homogenate could also present some evidence to the in vivo degradative mechanism of EM-2.

Analgesics↗

Amodal completion impairs stereoacuity discrimination.

Visual stimulus configuration can influence elementary visual processes. We provide empirical evidence to demonstrate this effect in stereoscopic depth discrimination. Two vertically aligned bars were presented in stereo such that one of them was closer to the human observer. Observers discriminated which of the two was closest. In the first, "occluded" condition, a horizontal bar, positioned closest in depth to the observer, was added to the display such that the two vertical bars perceptually completed to form a whole by connecting together behind the horizontal bar. In the second, control condition, the horizontal bar was placed furthest away from the observer such that there was a visible gap between the two vertical bars, which could no longer complete perceptually. We measured observers' psychometric functions using the method of constant stimuli, and found that their discrimination sensitivity d' was smaller when the two vertical bars perceptually completed than when they did not. We used a simple model to illustrate that when the two vertical bars perceptually completed, they also tended to be perceived as coplanar in the fronto-parallel plane. This consequence of completion made it more difficult to discriminate any difference in depth between the two vertical bars.

Analysis of Variance↗

Short-term synaptic plasticity in the rat geniculo-cortical pathway during development in vivo.

The critical period for visual system development in rats normally peaks at postnatal three weeks and ends at postnatal five weeks. However, the change of short-term synaptic plasticity during this period has rarely been investigated. In the present study, we compared the short-term plasticity of visual cortical responses to lateral geniculate nucleus stimulation in rats at different development stages (P20, P30 and adult) in vivo. The results show that paired-pulse depression (PPD) and frequency-dependent depression of evoked field potentials (FP) are present in P20 rats and increase in magnitude with development. The time course of this maturation of synaptic depression parallels that of the visual critical period. The weak synaptic depression observed in juvenile rats may be important in enhancing excitatory neurotransmission at a time when synapses are immature; this could endow immature synapses with wide integrative capabilities. In contrast, suppressive temporal interactions could provide an important substrate for neuronal processing of visual information in the mature cortex.

Animals↗

Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer.

The tumor suppressor TP53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage and oncogene activation. MDM2 is a key negative regulator of the TP53 pathway and is overexpressed in many cancers as oncoprotein. We investigated the association between genetic variation in the promoter region of MDM2 (c.-5+309G>T, rs2279744:g.G>T) and the coding region of TP53 (c.215G>C, rs1042522:g.G>C, designated Arg72Pro) and the risk of developing lung cancer. The genotypes of 1,106 patients and 1,420 controls were determined by tetra-primer amplification refractory mutation system (ARMS)-PCR or PCR-based restriction fragment length polymorphism (RFLP). Associations with risk of lung cancer were estimated by logistic regression. We observed an increased lung cancer risk associated with the MDM2 GG (odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.45-2.32) and TG (OR = 1.33, 95% CI = 1.09-1.63) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 1.47, 95% CI = 1.17-1.85, P = 0.003) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased lung cancer risk in a supermultiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 4.56, 95% CI = 2.76-7.54). Significant interactions were observed between these polymorphisms (respectively and jointly) and smoking (OR = 10.41, 95% CI = 5.26-20.58) for smokers with both the MDM2 GG and TP53 Pro/Pro genotypes. In conclusion, genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer.

Aged↗

Functional degradation of visual cortical cells in old cats.

Visual function declines with age. Using extracellular single-unit in vivo recordings, we compared the function of primary visual cortical (area 17) cells in young and old paralyzed, anesthetized cats. The results reveal that cortical neurons in old cats exhibit higher visually evoked responses, higher spontaneous activities, lower signal-to-noise ratios, and weaker orientation and direction selectivity than do cells in young adult cats. These findings are consistent with previously reported age related declines in cortical function in senescent macaque monkeys. Thus, similar declines in cortical function accompany old age in different mammalian species with well developed cortices.

Action Potentials↗

Chronic morphine exposure affects the visual response properties of V1 neurons in cat.

Chronic opiate exposure leads to maladaptive changes in brain function. In view of the localization of opiate receptors in mammalian visual system, chronic opiate exposure is likely to affect the visual responses properties of V1 neurons. Using in vivo single-unit recording, we here showed that chronic morphine treatment resulted in the functional abnormality of primary visual cortical cells. When compared with saline-treated (as control) cats, cortical neurons in morphine-treated cats exhibited higher spontaneous activity, lower signal-to-noise ratios and weaker orientation and direction selectivity. However, re-exposure with morphine could significantly improve the function of V1 neurons in morphine-treated cats. These findings demonstrated that chronic morphine treatment could significantly degrade the response properties of V1 neurons and may lead to a function dependence on morphine in visual cortical cells.

Animals↗

FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer.

The FAS receptor-ligand system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumor-immune escape and carcinogenesis. We have recently demonstrated (Sun, T., X. Miao, X. Zhang, W. Tan, P. Xiong, and D. Lin. 2004. J. Natl. Cancer Inst. 96:1030-1036; Zhang, X., X. Miao, T. Sun, W. Tan, S. Qu, P. Xiong, Y. Zhou, and D. Lin. 2005. J. Med. Genet. 42:479-484) that functional polymorphisms in FAS and FAS ligand (FASL) are associated with susceptibility to lung cancer and esophageal cancer; however, the mechanisms underlying this association have not been elucidated. We show that the FAS -1377G, FAS -670A, and FASL -844T variants are expressed more highly on ex vivo-stimulated T cells than the FAS -1377A, FAS -670G, and FASL -844C variants. Moreover, activation-induced cell death (AICD) of T cells carrying the FASL -844C allele was increased. We also found a threefold increased risk of cervical cancer among subjects with the FASL -844CC genotype compared with those with the -844TT genotype in a case-control study in Chinese women. Together, these observations suggest that genetic polymorphisms in the FAS-FASL pathway confer host susceptibility to cervical cancers, which might be caused by immune escape of tumor cells because of enhanced AICD of tumor-specific T cells.

Adult↗

Perceptual learning improves contrast sensitivity and visual acuity in adults with anisometropic amblyopia.

To evaluate the effects of perceptual learning on contrast-sensitivity function and visual acuity in adult observers with amblyopia, 23 anisometropic amblyopes with a mean age of 19.3 years were recruited and divided into three groups. Subjects in Group I were trained in grating detection in the amblyopic eye near pre-training cut-off spatial frequency. Group II received a training regimen of repeated contrast-sensitivity function measurements in the amblyopic eye. Group III received no training. We found that training substantially improved visual acuity and contrast-sensitivity functions in the amblyopic eyes of all the observers in Groups I and II, although no significant performance improvement was observed in Group III. For observers in Group I, performance improvements in the amblyopic eyes were broadly tuned in spatial frequency and generalized to the fellow eyes. The latter result was not found in Group II. In a few cases tested, improvements in visual acuity following training showed about 90% retention for at least 1 year. We concluded that the visual system of adult amblyopes might still retain substantial plasticity. Perceptual learning shows potential as a clinical tool for treating child and adult amblyopia.

Adolescent↗

Age-related effects of bromocriptine on sensory gating in rhesus monkeys.

Declines in dopamine neurotransmission are a robust characteristic of the process of normal aging. Using neuroimaging, biochemical and cognitive methods, age-related reduction of D2 receptor has been noted in a wide range of species. On the other hand, it is well known that dopamine plays a crucial role in the modulation of sensory gating. Here, we examined age-related alterations of D2 receptor in rhesus monkeys, using a sensory gating paradigm. The direct D2 receptor agonist, bromocriptine, was characterized in young adult and aged monkeys. We found bromocriptine disrupted sensory gating in young adult monkeys but not in aged ones. Our results provided new evidence that there is a functional decline of D2 receptor in aged monkeys.

Aging↗

Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status.

Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.

Adult↗

Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancer susceptibility.

Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer initiation and progression. Our previous studies revealed that the -1306C-->T and -735C-->T polymorphisms in MMP2 promoter significantly influence transcriptional activity and their genotypes and haplotypes are associated with susceptibility to several cancers. This case-control study examined the contribution of these two polymorphisms to the risk of developing lung cancer. MMP2 genotypes and haplotypes were determined in 770 cases and 777 controls and the associations with risk of lung cancer were estimated by logistic regression. We observed a 2-fold [odds ratio (OR), 2.12; 95% confidence interval (CI), 1.64-2.72] or 1.6-fold (OR, 1.57; 95% CI, 1.27-1.95) excess risk of developing lung cancer for the -1306CC or -735CC genotype carriers compared with non-carriers, respectively. A greater risk of lung cancer was associated with the C(-1306)-C(-735) haplotype (OR, 5.01; 95% CI, 2.57-9.78) compared with the T(-1306)-T(-735) haplotype, suggesting a synergic effect of these two polymorphisms. Furthermore, a greater than additive joint effect of the polymorphisms and smoking increased an even higher risk of lung cancer. The OR for smokers with the C(-1306)-C(-735) haplotype was 6.24 (95% CI, 4.51-8.64), which was significantly higher than that (OR, 4.10; 95% CI, 2.89-5.81) of smokers with the T(-1306) or T(-735)-containing haplotypes (P < 0.001). These results are consistent with our previous findings and further support the hypothesis that gain-of-function of MMP2 resulting from genetic polymorphisms plays an important role in human carcinogenesis.

Case-Control Studies↗

Degradation of signal timing in cortical areas V1 and V2 of senescent monkeys.

Senescence in monkeys results in a degradation of the functional properties of cortical cells as well as prolonged hyperactivity. We have now compared the spontaneous and visually evoked activity levels, as well as the visual response latencies of cells in cortical areas V1 and V2 of young and very old monkeys. We found that V1 cells within layer 4 exhibit normal latencies. In contrast, in other parts of V1 and throughout V2 hyperactivity in old monkeys is accompanied by dramatic delays in both the intracortical and intercortical transfer of information. Extrastriate cortex (area V2) is affected more severely than striate cortex (V1). Delayed information processing in cerebral cortex should contribute to the declines in cortical function that accompany old age.

Aging↗