PubMed Health⌕ Search

Biomedical subjects

Lin Yan

Publications and source records attributed to Lin Yan.

At least 19 recordsLinked to original sources

Latent preference for red ornamentation drives interspecific mating in nascent jumping spider species (Habronattus americanus group, F. Salticidae).

Heterospecific interactions between nascent species offer insights into how sexual selection shapes novel traits, illuminating patterns in species interactions and diversification. We tested female preferences between two recently diverged, allopatric species of jumping spiders: Habronattus americanus PLC, with red-coloured males performing short multimodal displays, and Habronattus sansoni CC, with brown-coloured males performing long multimodal displays. Mate choice experiments showed that females of both species preferred H. americanus PLC males. To examine the role of red coloration, we manipulated male coloration in both species. Results indicated that red-painted H. sansoni CC males experienced an increase in mating success, whereas brown-painted H. americanus PLCmales did not show reduced success. Our study suggests that (i) strong latent female preferences can drive unidirectional introgression across species boundaries, potentially leading to genomic homogenization; (ii) latent preferences may override preferences for existing traits; and (iii) the geographical distribution of colour morphs is consistent with a hypothesis of strong latent preferences across populations. Overall, our study demonstrates the role that mating interactions can play in speciation dynamics.

Animals↗

An efficient synthesis of quinoxaline derivatives from 4-chloro-4-deoxy-alpha-D-galactose and their cytotoxic activities.

A novel and efficient method for the synthesis of quinoxaline derivatives has been developed. Isopropylidenation of 4-chloro-4-deoxy-alpha-D-galactose with 2,2-dimethoxypropane, followed by selective hydrolysis, afforded 2,3-O-isopropylidene-4-chloro-4-deoxy-D-galactose di-methyl acetal (3) as a sole product. Oxidation of compound 3 with (Bu3Sn)2O-Br2 gave corresponding hex-5-ulose derivative in high yields. The hex-5-ulose derivative reacted with o-phenylenediamines under neutral conditions to afford quinoxaline derivatives in reasonable yields. The in vitro cytotoxic activities of these quinoxaline derivatives were investigated.

Antineoplastic Agents↗

Obligatory role of cardiac nerves and alpha1-adrenergic receptors for the second window of ischemic preconditioning in conscious pigs.

We tested the hypothesis that cardiac nerves may mediate ischemic preconditioning. Pigs were chronically instrumented to measure aortic, left atrial and left ventricular pressures, and regional myocardial function (wall thickening). Hemodynamic variables, area at risk, and tissue blood flows (radioactive microspheres) were similar among groups. Myocardial infarct size following 60 minutes coronary artery occlusion and 4 days reperfusion, expressed as a fraction of the area at risk, was 42+/-4.0%, in innervated pigs and similar in pigs with regional cardiac denervation (CD, 41+/-2.5%). Infarct size in innervated pigs during the first window of preconditioning (first window) was markedly reduced (6+/-1.8%, P<0.01), as it was in the second window of preconditioning (second window) (16+/-3.3%, P<0.01). Although infarct size was still reduced in pigs with CD and first window preconditioning (9+/-1.8%, P<0.01), the protective effects of second window were abrogated in pigs with CD resulting in an infarct size of 38+/-5.6%. In another group of innervated pigs during pharmacological alpha(1)-adrenergic receptor (AR) blockade, infarct size was also not reduced during the second window (48+/-3.2%). Additionally, Western blot analysis of inducible nitric oxide synthase and cyclooxygenase-2 proteins demonstrated significant (P<0.05) upregulation following the second window in innervated pigs, but not in pigs with CD or alpha(1)-AR blockade. Thus, the mechanism of protection during the second window, but not the first window, appears to be dependent on cardiac nerves and alpha(1)-AR stimulation.

Adrenergic alpha-1 Receptor Antagonists↗

SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties.

Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent.

Animals↗

Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy.

BACKGROUND: The adaptation of cardiac mass to hemodynamic overload requires an adaptation of protein turnover, ie, the balance between protein synthesis and degradation. We tested 2 hypotheses: (1) chronic left ventricular hypertrophy (LVH) activates the proteasome system of protein degradation, especially in the myocardium submitted to the highest wall stress, ie, the subendocardium, and (2) the proteasome system is required for the development of LVH. METHODS AND RESULTS: Gene and protein expression of proteasome subunits and proteasome activity were measured separately from left ventricular subendocardium and subepicardium, right ventricle, and peripheral tissues in a canine model of severe, chronic (2 years) LVH induced by aortic banding and then were compared with controls. Both gene and protein expressions of proteasome subunits were increased in LVH versus control (P<0.05), which was accompanied by a significant (P<0.05) increase in proteasome activity. Posttranslational modification of the proteasome was also detected by 2-dimensional gel electrophoresis. These changes were found specifically in left ventricular subendocardium but not in left ventricular subepicardium, right ventricle, or noncardiac tissues from the same animals. In a mouse model of chronic pressure overload, a 50% increase in heart mass and a 2-fold increase in proteasome activity (both P<0.05 versus sham) were induced. In that model, the proteasome inhibitor epoxomicin completely prevented LVH while blocking proteasome activation. CONCLUSIONS: The increase in proteasome expression and activity found during chronic pressure overload in myocardium submitted to higher stress is also required for the establishment of LVH.

Adaptation, Physiological↗

Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition.

We examined pressure overload left ventricular (LV) hypertrophy (H) induced by aortic banding in transgenic mice with cardiac-specific expression of a dominant negative (DN) p38alpha (TG) and wild type controls (WT). In response to chronic pressure overload, induced by aortic constriction, LV/BW increased more, p<0.05, in female TG (6.4+/-0.2, n=7) than in WT female (5.1+/-0.2, n=10), or male TG or WT (5.0+/-0.2, n=10 vs. 5.5+/-0.2, n=8). Lung/BW, an index of LV decompensation, was significantly higher, p<0.05, in banded female TG (14+/-1.2 mg/g) than in WT females (9.0+/-0.8), or male TG or WT (8.2+/-0.7 vs. 9.3+/-1.3). This was associated with higher premature mortality, p<0.05, in banded female TG mice (42%) compared with banded WT females (10%), TG males (13%), or WT males (17%). In male, but not female, TG mice, the number of TUNEL-positive cells was smaller, p<0.05, compared with WT. Phospho-Akt kinase activity increased (p<0.05) in female TG after banding, but not in males. After ovariectomy, chronic pressure overload no longer induced greater mortality, greater LVH, or p-Akt levels in female TG mice, and like male TG mice, apoptosis was protected. DN-p38alpha enhanced estrogen-induced activation of Akt in cultured cardiac myocytes. Thus, inhibition of p38alpha MAPK paradoxically augments LVH resulting in cardiac decompensation and increased mortality in response to pressure overload more in female mice than male mice, which could be due to increased Akt activation and/or through cross-talk between p38alpha MAPK and Akt.

Animals↗

Autophagy: a novel protective mechanism in chronic ischemia.

During the search for cardioprotective mechanisms in a porcine model of chronic myocardial ischemia and hibernating myocardium, we discovered evidence for autophagy, which could be involved in the protection against apoptosis. Autophagy is a cellular degradation process responsible for the turnover of unnecessary or dysfunctional organelles and cytoplasmic proteins, which become sequestered in a double-membrane-bound vesicle, termed autophagosome, and subsequently degrade upon fusion with lysosomes. The dauer phase in C. elegans shares similarities with the induction of autophagy in chronically ischemic (hibernating) myocardium. In this sense, autophagy is an essential mechanism for survival which is activated by environmental stresses and confers stress resistance to the organism. Our study provided insight into understanding of the protective mechanism of autophagy in chronic ischemia.

Adaptation, Physiological↗

Discovery of 3-arylpropionic acids as potent agonists of sphingosine-1-phosphate receptor-1 (S1P1) with high selectivity against all other known S1P receptor subtypes.

A series of 3-arylpropionic acids were synthesized as S1P1 receptor agonists. Structure-activity relationship studies on the pendant phenyl ring revealed several structural features offering selectivity of S1P1 binding against S1P2-5. These highly selective S1P1 agonists induced peripheral blood lymphocyte lowering in mice and one of them was found to be efficacious in a rat skin transplantation model, supporting that S1P1 agonism is primarily responsible for the immunosuppressive efficacy observed in preclinical animal models.

Animals↗

Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.

Animals↗

Generation of monoclonal antibodies and epitope mapping of ApxIVA of Actinobacillus pleuropneumoniae.

To study functions of ApxIV, a species-specific and in vivo inducible RTX toxin identified in Actinobacillus pleuropneumoniae recently, and to develop a diagnostic trial distinguishing the pigs infected naturally and vaccinated with inactivated and/or subunit vaccines, we attempted to prepare monoclonal antibodies against ApxIV. BALB/c mice were immunized with ApxIVAN and ApxIVAC which are N- and C-terminal halvies (814 and 997 amino acids, respectively) of ApxIVA produced in E. coli BL21 (DE3), respectively. Eight monoclonal antibodies were selected, four (designated as 1A8, 1G5, 3E7 and 4H9) against ApxIVAN and another four (named as 1B12, 2E5, 4D8 and 4G2) against ApxIVAC. Western blot and ELISA additivity assays suggested that all monoclonal antibodies except 1A8 are specific to the corresponding immunogen, 1A8 reacts with both immunogens which have a overlapping region of 156 residues. ELISA additivity tests revealed that at least five epitopes in ApxIV are defined by eight monoclonal antibodies, two between 1 and 866 amino acids, one between 867 and 1022 amino acids and two between 1023 and 1863 amino acids. In conclusion, we have succeeded in producing eight monoclonal antibodies, which react with five different epitopes of ApxIV.

Actinobacillus Infections↗

Role of CNS alpha1-adrenoceptor activity in central fos responses to novelty.

The present study investigated, by use of fos immunohistochemistry, whether the functional activity of alpha(1)-adrenoceptors is elevated during heightened behavioral activity in brain regions shown earlier to contain motoric alpha(1)-receptors. In confirmation, marked c-fos responses that were blocked by an alpha(1)-antagonist (prazosin) were found in four of these brain regions (secondary motor, cingulate, piriform cortices, and nucleus accumbens) of animals exposed to a mildly novel environment (clean cage), which elicits a high degree of sustained exploratory activity. Experimental restriction of exploratory activity in the novel cage by a small enclosure did not reduce the fos responses in these areas, and in fact, enhanced gene expression when carried out in home-caged animals suggesting that the fos response may be more closely associated with the motivation to be active rather than activity itself. Experiments with locally administered alpha(1)-agonists and antagonists in the cortex by reverse dialysis showed that the above mentioned alpha(1)-dependent-fos responses were the result of activation of local alpha(1)-receptors in these brain regions. Unlike the aforementioned brain regions, the fos response of the locus coeruleus was not blocked by prazosin, and this nucleus also showed a marked fos increase to prazosin itself possibly as a compensatory response to the blockade of forebrain alpha(1)-receptors.

Adrenergic alpha-Antagonists↗

HPLC determination and steady-state bioavailability study of levodropropizine sustained-release tablets in dogs.

A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) in dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol-diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with H3PO4) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV %) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be 106.3 +/- 12.8% (n=6). The Cmax of the SR was significantly lower (P<0.05), and the tmax was significantly longer than that of the IR (P<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.

Animals↗

[Study on Meta analysis regarding the acceptability of medical abortion compared with surgical abortion].

OBJECTIVE: To analyze and evaluate the acceptability of mifepristone compatible with misoprostone versus conventional surgical abortion among women under unwanted early pregnancy, so as to help the unexpected pregnant women to choose the satisfactory abortion, and to provide the evidence for clinicians to make a proper clinical decision. METHODS: Six medical databases were searched, including MEDLINE, EMBASE, Cochrane library, CBMdisc, CNKI and VIP, together with twelve journals hand-searched, and references of included studies additionally searched. Two qualified reviewers reviewed the original articles, evaluating qualities of articles, and extracting data independently. After heterogeneity test, the data was pooled using Revman software if capable, or descriptive analysis was applied. RESULTS: In total, nine original clinical controlled trials were included, containing 3565 cases. Before abortion, more unwanted pregnant women chose the medical abortion because they believed medical abortion was less painful than surgical abortion (OR = 466.51, 95% CI: 91.37 - 2381.88), but medical abortion was less time-consuming than surgical abortion (OR = 0.02, 95% CI: 0.01 - 0.06). After abortion, satisfaction with medical abortion was similar to that with surgical abortion, with insignificant difference (P = 0.89). However, second choice and recommendation rates of medical abortion were much higher than those of surgical abortion with OR and 95% CI as 2.72, 2.13 - 3.47 and 4.19, 2.16 - 11.16, respectively. CONCLUSIONS: Medical abortion was less painful than surgical abortion and the rate of second choice and recommendation to others were all also higher than those of surgical abortion. However, the process of medical abortion was not as quick as surgical abortion but the satifacation of both methods seemed similar. Therefore, the two artificial abortion methods were not recommended to replace each other at the present time.

Abortifacient Agents↗

[Study on apoptosis of oral squamous carcinoma cell line KB and KBv200 induced by survivin RNAi].

BACKGROUND & OBJECTIVE: Survivin, a member of IAPs (inhibition of apoptosis proteins) family, has been revealed by many studies to inhibit the activation of caspase-3, caspase-7 and caspase-9, and thus increase the anti-apoptotic effect of cancer cells, which subsequently makes the cells to become resistant to chemotherapy in cancer treatment. Survivin is expressed in human oral squamous carcinoma cell line KB and its multiple-drug resistant (MDR) cell line KBv200. This study was to compare the apoptosis induced by silencing survivin gene between these two squamous cell lines. METHODS: Mu6/survivin plasmid which expressed shRNA against survivin was transfected into both KB and KBv200 cells to inhibit the expression of survivin gene. Survivin mRNA and protein expression was detected by semi-quantitative RT-PCR and flow cytometry (FCM), respectively. Cell apoptotic rate was measured by flow cytometry after PI staining, and apoptotic morphology of cells was observed under a fluorescent microscope after Hoechst33258 staining. Activation of caspase-3 was measured by colorimetric assay. MTT was used to evaluate the growth inhibition of tumor cells. RESULTS: Expression of survivin, which was higher in KBv200 at mRNA and protein level, was detected in both KB and KBv200. After 48 h transfection with mu6/survivin plasmid, the expression level of survivin mRNA in KB and KBv200 was reduced by (61.98+/-8.12)% and (59.29+/-6.32)%; and that of survivin protein was decreased by (44.25+/-5.26)% and (38.76+/-4.31)% compared with the control group. Moreover, KB and KBv200 cells exhibited typical apoptotic cell morphology by Hoechst 33258 staining. Apoptosis, which was higher in KB cells, was increased significantly at 24, 48, 72 h after the transfection of mu6/surviving in KB and KBv200 cells, and reached the peak at 48 h. Similarly, activation of caspase-3 was elevated significantly, and reached the peak at 48 h. MTT assay revealed the inhibitory rates were (33.04+/-2.16)%, (56.25+/-3.32)% and (58.26+/-5.14)% in KB cells, and (35.23+/-3.42)%, (44.90+/-4.12)% and (44.19+/-4.37)% in KBv200 cells at 24, 48, 72 h after the transfection, respectively. Growth rate was lower in KB cells at 48, 72 h after the transfection compared with KBv200 cells. CONCLUSION: RNA interference could silence the expression of survivin, which significantly induces apoptosis not only in KB cells, but also in drug resistant KBv200 cells.

Antineoplastic Agents↗

Highly stereoselective synthesis and structural characterization of new amino sugar derivatives.

2-C-Nitroalkyl-1,4:3,6-dianhydromannitols were synthesized via a Henry reaction of nitroalkyls with 1,4:3,6-dianhydrofructose. Catalytic hydrogenation then afforded the corresponding vicinal amino alcohols. Oximation of 1,4:3,6-dianhydrofructose with hydroxylamine, followed by hydrogenation, gave 2-amino-1,4:3,6-dianhydro-2-deoxymannitol. All compounds were elucidated by their HRMS, 1H NMR, 13C NMR, and IR spectra. The absolute configurations of the amino sugar derivatives were confirmed by single-crystal X-ray analysis or NOESY spectral studies. The possible mechanism for hydrogenation of the nitro 2-C-nitroalkyl sugar is proposed. The conformations of the fused furan rings of nitro and amino sugar derivatives are presented.

Amino Sugars↗

Meta-analysis of soy food and risk of prostate cancer in men.

There has been considerable interest in recent years in the role of soy in cancer etiology. The purpose of this meta-analysis was to evaluate epidemiologic studies available to date that related soy consumption to the risk of prostate cancer in men. We conducted a thorough Medline search for English-language publications, supplemented with hand-searching of articles' bibliographies and nonindexed medical and professional journals, on epidemiologic studies of soy and prostate cancer. We identified 2 cohort and 6 case-control studies that met the following criteria for meta-analysis: a study must have assessed soy as a food and provided a risk estimate (relative risk or odds ratio) and its 95% confidence interval. Data from the same study population appearing in different journals were only used once with the most recent publication chosen for the analysis. Studies on fermented soy food were not included. We conducted the meta-analysis using a random-effects model. An analysis of these studies yielded an overall risk estimate of 0.70 (95% CI = 0.59-0.83; p < 0.001). No publication bias was detected. In summary, results of the analysis showed that consumption of soy food was associated with a lower risk of prostate cancer in men.

Cohort Studies↗