[Research progress on signaling pathways related to drug research in proliferative vitreoretinopathy].

Proliferative vitreoretinopathy (PVR) is an avascular fibroproliferative disease that occurs in the retina. The main pathological changes are the proliferation and traction of retinal pigment epithelial cells (RPE) and glial cells on the vitreous and retina. Basic research has confirmed that the formation of PVR is related to multiple signaling pathways, including NK-κB signaling pathway, MAPK and its downstream signaling pathways, JAK/STAT signaling pathway, PI3K/Akt signaling pathway, thrombin and its receptor pathway, TGF-ß and downstream signaling pathway, North signaling pathway and Wnt/ß-catenin signaling pathway, etc. This review summarizes the research progress of the main signaling pathways in the formation mechanism of PVR, and provides the basis and support for the research of PVR drug therapy.

[Observational study on peripapillary hyper-reflective ovoid mass-like structures in children and adolescents with myopia].

Objective: To investigate the correlation of peripapillary hyper-reflective ovoid mass-like structures (PHOMS) in children and adolescents with myopia and its correlation factors. Methods: It was a cross-sectional study. From September 2021 to January 2022, myopic children and adolescents aged 6-16 years treated in Wuhan Central Hospital and Renmin Hospital of Wuhan University with a myopic spherical equivalent (SE) ≥0.5 D were consecutively included. All patients underwent best corrected visual acuity, refraction, intraocular pressure, slit lamp microscope, axial length, fundus photography and enhanced depth imaging optical coherence tomography (EDI-OCT) examination. EDI-OCT optic disc parameter measurements included diameter, degree of tilt and shift and PHOMS height. The patients were divided into PHOMS group and non-PHOMS group according to the presence or absence of PHOMS. According to the height of PHOMS, the patients were further divided into 3 subgroups: large (>400 µm), medium (200-400 µm) and small (<200 µm). The optic disc characteristics of the PHOMS group and the non-PHOMS group and each subgroup were observed, and the correlation factors of PHOMS were analyzed. Mann-Whitney U test, Kruskal-Wallis test, chi-square test, Logistic regression analysis and Kendall's tau-b correlation coefficient were used. Results: A total of 108 patients (108 eyes) were included, including 46 males (46 eyes) and 62 females (62 eyes). There were 70 eyes (64.8%) in the PHOMS group and 38 eyes (35.2%) in the non-PHOMS group. Small PHOMS can only be detected by EDI-OCT, while medium to large PHOMS showed blurred optic disc boundaries on fundoscopy images. Univariate Logistic regression analysis showed that PHOMS was associated with age (OR=1.36, 95%CI: 1.13-1.65, P=0.001) and myopic SE (OR=4.57, 95%CI: 2.51-8.32, P<0.001), axial length (OR=2.28, 95%CI: 1.37-3.82, P=0.002), optic disc tilt (OR=3.44, 95%CI: 2.09-5.66, P<0.001), optic disc shift (OR=0.95, 95%CI: 0.93-0.98, P<0.001) and optic disc diameter (OR=0.75, 95%CI: 0.58-0.95, P=0.019). Multivariate Logistic regression analysis showed that the higher the myopic SE (OR=3.01, 95%CI: 1.27-7.17, P=0.013) and the greater the tilt of the optic disc (OR=4.06,95%CI:1.99-8.29,P<0.001), the higher the risk of PHOMS. Kendall's tau-b correlation coefficient analysis showed that the height of PHOMS was negatively correlated with optic disc shift (r=-0.31, P<0.001). Conclusions: PHOMS can be found in a subset of myopic children. The fundus manifestations of PHOMS of different heights are slightly different. The large myopic SE and great optic disc tilt are risk factors of PHOMS, and their magnitudes correlate with the border tissue angle.

[The association between blood homocysteine level and Chinese Healthy Eating Index in a suburb population of Shanghai].

Objective: To explore the relationship between the level of blood homocysteine (Hcy) and the total score of Chinese Healthy Eating Index (CHEI) and its item score. Methods: The subjects were recruited from the East China Natural Population Cohort Study, led by the School of Public Health in Fudan University, which was conducted in Zhongshan Community, Songjiang District of Shanghai from April to September 2017. By using the cluster random sampling method, 8 neighborhood committees were randomly selected from 18 neighborhood committees in Zhongshan community (Beimen, Baiyun, Dongwai, Huaqiao, Lantian village 1, Lantian village 2, Lantian village 4, and Lantian village 5). All the residents who met the standard and had lived in Shanghai for more than half a year were selected as research subjects. 4 995 subjects with complete survey information were finally included in this study. General information (age, sex, disease history, etc.), lifestyle (smoking, drinking, tea drinking, physical activity, etc.), food frequency and blood Hcy concentration were collected through questionnaire survey, physical examination and biological sample detection. The multivariate linear regression model was used to analyze the correlation between blood Hcy concentration and the total score of CHEI and its item score, and the multivariate logistics regression model was used to analyze the correlation between hyperhomocysteinemia (hHcy) and the total score of CHEI and its item score. Results: The age of the subjects was (56.72±9.72) years. The proportion of females, people with middle and high school education and high physical activity was 64.90% (3 241), 50.80% (2 539) and 63.20% (3 157), respectively. The blood Hcy concentration was (11.25±4.90) µmol/L, and the total prevalence of hHcy was 9.3% (467 cases). The results of multivariate linear regression showed that after adjusting for the relevant confounding factors, the blood Hcy concentration of subjects decreased with the increase of the total score of CHEI and the item score of fruit, milk, seafood, poultry and egg, but increased with the increase of the item score of total grain and tuber. In males, blood Hcy levels decreased with the increase of the item score of seafood and poultry [ß (95%CI) values were -0.343 (-0.582, -0.102) and -0.225 (-0.402, -0.046), respectively]. In females, the blood Hcy level decreased with the increase of the total score of CHEI and its item score of milk, egg, seafood and poultry [ß (95%CI) values were -0.130 (-0.207, -0.052), -0.091 (-0.148, -0.034), -0.016 (-0.026, -0.007), -0.069 (-0.122, -0.016), and -0.087 (-0.157, -0.017), respectively]. The results of multivariate logistic regression showed that the higher the total score of CHEI and its item score of milk and seafood, the lower the risk of hHcy [OR (95%CI) value were 0.986 (0.978, 0.995), 0.915 (0.864, 0.969), and 0.862 (0.806, 0.922), respectively]. In females, the higher the total score of CHEI and its item score of milk and seafood, the lower the risk of hHcy [OR (95%CI) values were 0.984 (0.970, 0.999), 0.877 (0.802, 0.958), and 0.845 (0.760, 0.941), respectively]. In males, the higher the total score of CHEI and its item score of seafood, the lower the risk of hHcy [OR (95%CI) values were 0.988 (0.977, 0.998) and 0.858 (0.791, 0.930), respectively]. Conclusion: The dietary pattern of residents in Zhongshan Community, Songjiang District, Shanghai can affect their own blood Hcy concentration and the risk of hHcy. The total score of CHEI and the item score of fruit, milk, seafood, poultry and eggs play an important role in reducing the level of blood Hcy. The higher the total score of CHEI and the item score of milk and seafood, the lower the risk of hHcy.

The structure and functions of paxillin and its roles in neovascularization.

Identifying and studying the molecular mechanisms of neovascularization biomarkers are critical for conquering many diseases, such as corneal diseases and cancer. Paxillin is an important cell scaffold and cellular signaling protein, especially a key molecule of the Integrin-mediated downstream signaling transduction. This review summarizes the structure and functions of paxillin, and the research progress of its roles in neovascularization. Although there are still some problems to be solved, paxillin may become an important target of anti-neovascularization therapies.

Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.

Neuroprotective effect of ketamine on acute spinal cord injury in rats.

The aim of this study was to investigate the neuroprotective effects of ketamine during acute spinal cord injury in rats. Sprague Dawley (SD) rats (N = 70) were randomly divided into three groups: sham-operated (N = 10), control (N = 30), and treatment (N = 30) groups. The moderate spinal cord injury model was established. After injury, the sham-operated group received no drug, the treatment group received intraperitoneal ketamine injections, and the control group received intraperitoneal normal saline injections. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and spinal cord malondialdehyde (MDA) were assessed, and nerve cell apoptosis was evaluated in each group at varying time points. After spinal cord injury, TNF-α, IL-6, and MDA levels, and the number of TUNEL-positive cells among 2500 cells significantly increased (P < 0.05). Further, compared with the control group, the treatment group showed significantly lower TNF-α, IL-6, and MDA levels, and fewer TUNEL-positive cells among 2500 cells at each time point (P < 0.05). Our data indicate that ketamine exerts a neuroprotective effect on injured spinal cord.

Betulin inhibits pro-inflammatory cytokines expression through activation STAT3 signaling pathway in human cardiac cells.

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is an important regulator of cardiac survival pathways. Decreased expression or activity of STAT3 in patients with end-stage heart failure demonstrated a clinical relevance of STAT3 in cardiac diseases. Betulin, a pentacyclic triterpene, has drawn extensive attention towards its beneficial effects. However, little is known about its roles in cardiac cells. MATERIALS AND METHODS: We investigated the effects of betulin on the pro-inflammatory processes in human cardiac AC16 cells. Genes expression of pro-inflammatory cytokines and activation of NF-κB signaling were analyzed. Besides, levels of phosphorylated STAT3 and its down-stream target genes were measured to evaluate the activation of STAT3. Finally, STAT3 inhibitor and small interfering RNA (siRNA) oligos were used to determine the roles of STAT3 in AC16 cells treated with betulin. RESULTS: Our results revealed that betulin inhibited pro-inflammatory cytokines expression and NF-κB signaling activation through STAT3 signaling. Besides, betulin treatment also induced the expression of Bcl-xL, an anti-apoptotic downstream effector of STAT3. CONCLUSIONS: Our results, for the first time, uncovered the cardioprotective roles of betulin, which may be useful to reduce the occurrence of adverse cardiovascular events.

Anti-CD11c antibody, Efalizumab attenuate ventilator-induced lung injury.

BACKGROUND: The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation and inflammatory cells infiltration. The anti-CD11c monoclonal antibody, Efalizumab has been demonstrated to inhibit the T cell activation, migration and adhesion to keratinocytes. MATERIALS AND METHODS: In this study, we induced lung injury with mechanical ventilation in male Sprague-Dawley rats, the rats were divided into four groups: lung-protective ventilation (LV), injurious ventilation (HV), HV+human IgG control and HV+ Efalizumab groups. Then we detected the lung tissue wet/dry ratio, and the activity of myeloperoxidase (MPO) was determined. The concentration of protein, TNF-a, IL-6, IL-1b and MIP-2 in the BALF were detected by ELISA. The expression ICAM-1 was measured by Realtime PCR. RESULTS: Compared with the human IgG control treated group, the treatment of Efalizumab attenuate the ventilator-induced lung injury, including the wet/dry ratio and the activity of myeloperoxidase (MPO), meanwhile, the level of pro-inflammatory cytokines, such as TNF-a, IL-6, IL-1b and MIP-2 were decreased in the BALF of Efalizumab-treated group rats compared with the human IgG-treated control group. In addition, the histopathological index of ventilator-induced lung injury was improved after efalizumab treatment, that also reduced the recruitment of inflammatory cells into the lung, such as neutrophils. CONCLUSIONS: Our data suggested that Efalizumab could protect rat from ventilator-induced lung injury and improve the survival time through the inhibition of intrapulmonary inflammatory response.

Wave propagation in layered piezoelectric rectangular bar: an extended orthogonal polynomial approach.

Wave propagation in multilayered piezoelectric structures has received much attention in past forty years. But the research objects of previous research works are only for semi-infinite structures and one-dimensional structures, i.e., structures with a finite dimension in only one direction, such as horizontally infinite flat plates and axially infinite hollow cylinders. This paper proposes an extension of the orthogonal polynomial series approach to solve the wave propagation problem in a two-dimensional (2-D) piezoelectric structure, namely, a multilayered piezoelectric bar with a rectangular cross-section. Through numerical comparison with the available reference results for a purely elastic multilayered rectangular bar, the validity of the extended polynomial series approach is illustrated. The dispersion curves and electric potential distributions of various multilayered piezoelectric rectangular bars are calculated to reveal their wave propagation characteristics.

Modeling of MEMS resonator piezoelectric disc by means of an equicharge current source method.

The Legendre polynomial method has been extended to the modeling of MEMS resonator disc with current excitation (equicharge current source). Formulation is given that allows the electric current source to be taken into account. A unique formalism has been developed which allows for both harmonic and modal analyses. Numerical results such as normalized electric input impedance, resonant and anti-resonant frequencies, dispersion curves and displacement profiles are presented and compared with those obtained by using voltage excitation in order to check the accuracy and range of applicability of the proposed approach.

Genetic association of UBE2B variants with susceptibility to male infertility in a Northeast Chinese population.

The ubiquitin-conjugating enzyme 2B gene (UBE2B) is involved in the regular and symmetric organization of the fibrous sheath of sperm flagella. This study aimed to examine the relationship between single nucleotide polymorphisms (SNPs) in UBE2B and infertility in Northeast Chinese men. We carried out a polymerase chain reaction-restriction fragment length polymorphism analysis for SNPs in 312 fertile males and 388 infertile males in Northeast China. Taking advantage of the high degree of linkage disequilibrium among SNPs surrounding UBE2B (r(2) > 0.90), we selected 2 haplotype-tagging SNPs with a minor allele frequency of 5% or greater (rs17167484: g.-293T>G and rs3777373: g.20016A>G) that captured the majority of the genetic variations in a 40-kbp region of this gene. No significant differences between cases and controls were found in the allelic and genotype distribution of the 2 SNPs. However, the haplotype analysis for the 2 SNPs showed that the GA haplotype was significantly associated with a greater than 3-fold decreased risk of male infertility (P = 0.003). Because the frequency of the GA haplotype (1.1%) is relatively low in Chinese men, such a significant finding may occur by chance, but the results are still significant after multiple comparison adjustments (P = 0.012 after Bonferroni's correction). We conclude that the UBE2B polymorphisms g.-293T>G, g.20016A>G and g.9157A>G are not associated with male infertility, and the GA haplotype is likely a protective factor for male fertility in Northeast Chinese men.

Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.

Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARgamma ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness.

A systematic investigation into the extraction of aluminum from coal spoil through kaolinite.

This research has applied kaolin and active carbon (AC) to the investigation of the recovery of aluminum from coal spoil (CS). The kaolin, AC-containing kaolin mixture, and CS have been calcined at 500, 600, 700, 800, and 900 degrees C for 15, 30, 60, and 120 min. The transformation of kaolinite and aluminum extraction that occurred in each calcined sample have been characterized using XRD, TG, IR, and hydrochloric acid leaching methods. The dehydroxylation of kaolinite and the decomposition of metakaolin were influenced by thermal treatment temperature and time. The metakaolin had kept a portion of OH- in its structure until it was calcined at a temperature of 800 degrees C. Under 60 min treatment, new SiO2 phase was able to be formed at 500 degrees C, kaolinite was totally converted to metakaolin at 600 degrees C, and the SiO2 rejoined the reaction at 800 degrees C. The decompositions of CS were similar to those of kaolin mixture containing 20 wt % AC (MKC). The combustion of combustible matter accelerated the decomposition of kaolinite in the CS and MKC. Higher AC content led to lower aluminum extraction. The treatment at 600 degrees C was optimal for both CS and MKC.

Dual purinergic synaptic transmission in the human enteric nervous system.

Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca(2+) levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+) imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+) response. Short-circuit current (I(sc) = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons responding to high-K(+) depolarization from 61 surgical cases. FTS evoked synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency-dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or = 100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{[3-(4-fluorosulphonyl)benzoyl]-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic transmission in the huENS.

Mechanical stimulation activates Galphaq signaling pathways and 5-hydroxytryptamine release from human carcinoid BON cells.

5-Hydroxytryptamine (5-HT) released from enterochromaffin cells activates secretory and peristaltic reflexes necessary for lubrication and propulsion of intestinal luminal contents. The aim of this study was to identify mechanosensitive intracellular signaling pathways that regulate 5-HT release. Human carcinoid BON cells displayed 5-HT immunoreactivity associated with granules dispersed throughout the cells or at the borders. Mechanical stimulation by rotational shaking released 5-HT from BON cells or from guinea pig jejunum during neural blockade with tetrodotoxin. In streptolysin O-permeabilized cells, guanosine 5'-O- (2-thiodiphosphate) (GDP-beta-S) and a synthetic peptide derived from the COOH terminus of Galphaq abolished mechanically evoked 5-HT release, while the NH(2)-terminal peptide did not. An antisense phosphorothioated oligonucleotide targeted to a unique sequence of Galphaq abolished mechanically evoked 5-HT release and reduced Galphaq protein levels without affecting the expression of Galpha(11). Depletion and chelation of extracellular calcium did not alter mechanically evoked 5-HT release, whereas depletion of intracellular calcium stores by thapsigargin and chelation of intracellular calcium by 1,2-bis (o-Aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM) reduced 5-HT release. Mechanically evoked 5-HT release was inhibited by somatostatin-14 in a concentration-dependent manner. The results suggest that mechanical stimulation of enterochromaffin-derived BON cells directly or indirectly stimulates a G protein-coupled receptor that activates Galphaq, mobilizes intracellular calcium, and causes 5-HT release.

Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system.

Adenosine receptors (ADORs) in the enteric nervous system may be of importance in the control of motor and secretomotor functions. Gene expression and distribution of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was investigated using immunochemical, Western blotting, RT-PCR, and short-circuit current (I(sc)) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were differentially expressed in neural and nonneural layers of the jejunum, ileum, colon, and cecum and in HT-29, T-84, T98G, and Bon cell lines. A1R, A2aR, A2bR, and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5-immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR occurs in 57% of substance P-positive jejunal submucosal neurons (putative intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are coexpressed in enteric neurons and epithelial cells. 5'-N-methylcarboxamidoadenosine or carbachol evoked an increase in I(sc). A2bR IR is more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional differences also exist in smooth muscle expression of ADOR IR(s). It is concluded that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the regulation of neural reflexes in the human gut. Clear cell and regional differences exist in ADOR gene expression, distribution, localization, and coexpression.

Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women.

Elevation of plasma nonesterified fatty acid (NEFA) levels has been shown in various studies to induce peripheral tissue insulin resistance and impair the suppression of endogenous glucose production (EGP). These studies have been conducted predominantly in men. We compared the effects of elevated plasma NEFA levels on basal and insulin-stimulated glucose metabolism in 8 normal women (age 42 +/- 8 years [mean +/- SD], BMI 25 +/- 3 kg/m(2)) and 10 normal men (35 +/- 6 years, 24 +/- 3 kg/m(2)). Each subject underwent two 5-h 80 mU. m(-2). min(-1) hyperinsulinemic-euglycemic clamps with measurement of glucose kinetics (intravenous [3-(3)H]glucose) and substrate oxidation. Plasma NEFA levels were elevated in one study for 3 h before and during the clamp ( approximately 1 mmol/l in both groups) by infusion of 20% Intralipid (60 ml/h) and heparin (900 U/h). In the control studies, the men and women had similar insulin-stimulated glucose disposal rates (R(d)) and substrate oxidation rates. In the men, elevated NEFA levels decreased insulin-stimulated glucose R(d) during the final 40 min of the clamp by 23% (P < 0.001). By contrast, no significant change in glucose R(d) was found in the women (control 10.4 +/- 1.1, lipid study 9.9 +/- 1.3 mg. kg(-1). min(-1)). Glucose R(d) was also unchanged in six women studied at a lower insulin dose (40 mU. m(-2). min(-1)). During the last 40 min of the high-insulin dose clamps with elevated NEFA, glucose oxidation was decreased by 33% in the men (P < 0.001) and by 23% in the women (P < 0.02). Nonoxidative glucose R(d) at this time was decreased by 15% in the men (P = 0.02) but was not significantly affected in women. Basal EGP was unaffected by elevation of plasma NEFA levels in both groups. Suppression of EGP during the glucose clamps, however, was impaired. At the insulin infusion rate used, the magnitude of this defect was comparable in men and women. In summary, our findings suggest that although the effects on EGP appear comparable, the inhibitory effects of NEFA on peripheral tissue insulin sensitivity are observed in men but cannot be demonstrated in women.

Melanocortin-1 receptor gene variants in four Chinese ethnic populations.

There is strong relationship between melanocortin-1 receptor (MC1R) gene variants and human hair color and skin type. Based on a sequencing study of MC1R gene in 50 individuals from the Uygur, Tibetan, Wa and Dai ethnic populations, we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu, Arg67Gln, Val92Met, Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G), among which C414T and Ala299Val were reported for the first time. Confirmation and analysis were also made of 122 individuals at three common point mutations (Val92Met, Arg163Gln, A942G) using PCR-SSCP. The frequency of Arg163Gln variant varies in the four ethnic populations, with percentage of 40%, 85.0%, 66.2% and 72.7%, respectively, while those of Val92Met and A942G are roughly similar in these four populations. The different environments, migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

Annonaceous acetogenins of the seeds from Annona muricata.

Muricatenol (1) is a new C37 non-THF ring acetogenin with four hydroxyls and one isolated double bond in the long aliphatic chain. 2,4-cis-Gigantetrocinone (2) and 2,4-trans-gigantetrocinone (3) have been isolated as their acetates by preparative TLC. 2,4-trans-Isoannonacin-10-one (4) and 2,4-trans-isoannonacin (5) have been isolated as only 2,4-trans-form for the first time (no cis-form). Also four known acetogenins, gigantetrocin-A (6), gigantetrocin-B (7), annomontacin (8), gigantetronenin (9) and a mixture of N-fatty acyl tryptamines have been isolated (10). Their structures have been established on the basis of spectral analyses. The CHCl3 fraction of the seeds showed strong antitumor activities.

[Studies on the chemical constituents of the seeds from Artabostrys hexapetalus (Annonaceae)].

AIM: To study the chemical constituents of the seeds from Artabotrys hexapetalus (L.f.) Bhandari (Annonaceae). METHODS: Various chromatographic techniques were used to separate and purify the constituents. Their structures were elucidated on the physico-chemical properties and spectral data. RESULTS: Eight compounds were isolated from the seeds of A. hexapetalus. They were identified as four neolignans: isoamericanin A (1), isoamericanol A (2), americanin B (3) and artabotrycinol (4), a semiterpenoid: (R)-artabotriol (5) and others: palmitic acid (6), beta-sitosterol (7) and daucosterol (8). CONCLUSION: Artabotrycinol (4) and (R)-artabotriol (5) are new compounds. Three other neolignans were isolated from this plant for the first time.