The mechanisms of action of interleukin-1 on rabbit intestinal epithelial cells

Interleukin-1 (IL-1) is an inflammatory mediator that increases Cl- secretion in intestinal epithelial cells. To identify the signal transduction pathway(s) involved in IL-1's action, cells were treated with IL-1 and the levels of cyclooxygenase (COX) enzymes, prostaglandin E2 (PGE2) and phospholipase A2-activating protein (PLAP), and the activity of phospholipase A2 (PLA2) were measured. IL-1 caused concentration- and time-dependent increases in the levels of PLA2 activity, and/or in the levels of PLAP, COX-2 and PGE2. The IL-induced increase in PGE2 levels was biphasic, with the first peak due to the increase in PLAP levels, and the second peak due to the increase in COX-2 levels. This increase in PGE2 levels may provide a mechanism for acute and chronic inflammation in the intestine.     

Bone morphogenetic protein 2 may be a good predictor of success in oocyte fertilization during assisted reproductive technology

The aim of this study was to determine whether the bone-morphogenetic proreins-2 (BMP-2) or -7 (BMP-7) levels in follicular fluid (FF) are associated with success in oocyte fertilization during assisted reproductive technology (ART) treatment. Twenty-four cycles in 24 patients who underwent oocyte retrieval in Sugiyama clinic were included in this retrospective study. The patients were divided into two groups according to the success or failure of fertilization. FF samples were obtained from a single follicle in each patient, and the levels of BMP-2, BMP-7, Anti-Müllerian hormone (AMH), estradiol and progesterone from FF were measured, and evaluated in relation to the ART outcomes. The BMP-2 levels correlated positively with the AMH levels in FF (r(2) = 0.4928), but there was no statistically significant difference between BMP-7 and AMH levels. The BMP-2 and BMP-7 levels had no relation with either progesterone or estradiol levels, but BMP-2 levels in the fertilized group were significantly higher than those in the unfertilized group (P < 0.05). The BMP-2 levels in FF positively correlated with the AMH levels in FF, and those in the fertilized group were significantly higher than in the unfertilized group. Therefore, the BMP-2 levels in FF could be a predictive marker for fertilization.     

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase. High density lipoprotein characterization and gender-specific effects of apolipoprotein e genotype

Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C) (10-15 mg/dL lower than those of Americans or Western Europeans) associated with elevated hepatic lipase mass and activity. Here we report that Turks have low levels of high density lipoprotein subclass 2 (HDL(2)), apoA-I-containing lipoproteins (LpA-I), and pre-beta-1 HDL and increased levels of HDL(3) and LpA-I/A-II particles (potentially an atherogenic lipid profile). The frequency distributions of HDL-C and LpA-I levels were skewed toward bimodality in Turkish women but were unimodal in Turkish men. The apoE genotype affected HDL-C and LpA-I levels in women only. In women, but not men, the varepsilon2 allele was strikingly more prevalent in those with the highest levels of HDL-C and LpA-I than in those with the lowest levels. The higher prevalence of the epsilon2 allele in these subgroups of women was not explained by plasma triglyceride levels, total cholesterol levels, age, or body mass index. The modulating effects of apoE isoforms on lipolytic hydrolysis of HDL by hepatic lipase (apoE2 preventing efficient hydrolysis) or on lipoprotein receptor binding (apoE2 interacting poorly with the low density lipoprotein receptors) may account for differences in HDL-C levels in Turkish women (the epsilon2 allele being associated with higher HDL levels). In Turkish men, who have substantially higher levels of hepatic lipase activity than women, the modulating effect of apoE may be overwhelmed. The gender-specific impact of the apoE genotype on HDL-C and LpA-I levels in association with elevated levels of hepatic lipase provides new insights into the metabolism of HDL.     

The levels of prostaglandins associated with the reproductive cycle of the scallop, Patinopecten yessoensis

The present experiment was undertaken to investigate the seasonal variations of levels of prostaglandins (PGs) and regulation of these levels in the ovary and hemolymph of the scallop. The levels of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) in the hemolymph and ovary increased during sexual maturation, and these levels in the ovary showed a marked increase in the spawning season. Consecutive administration of antiestrogen inhibited the increase of the levels of PGF2 alpha and PGE2 during sexual maturation. These results indicate that the seasonal variations of the levels of PGF2 alpha and PGE2 are closely related to the reproductive cycle, suggesting that PGF2 alpha and PGE2 may be involved in the sexual maturation and spawning of the scallop. Furthermore, it was supposed that estrogen likely plays a role in the regulation of PGs production in female, well known in mammals.     

Laying-sequence-specific variation in yolk oestrogen levels, and relationship to plasma oestrogen in female zebra finches (Taeniopygia guttata)

We investigated the relationship between plasma and yolk oestrogens in laying female zebra finches (Taeniopygia guttata) by manipulating plasma oestradiol (E2) levels, via injection of oestradiol-17beta, in a sequence-specific manner to maintain chronically high plasma levels for later-developing eggs (contrasting with the endogenous pattern of decreasing plasma E2 concentrations during laying). We report systematic variation in yolk oestrogen concentrations, in relation to laying sequence, similar to that widely reported for androgenic steroids. In sham-manipulated females, yolk E2 concentrations decreased with laying sequence. However, in E2-treated females plasma E2 levels were higher during the period of rapid yolk development of later-laid eggs, compared with control females. As a consequence, we reversed the laying-sequence-specific pattern of yolk E2: in E2-treated females, yolk E2 concentrations increased with laying-sequence. In general therefore, yolk E2 levels were a direct reflection of plasma E2 levels. However, in control females there was some inter-individual variability in the endogenous pattern of plasma E2 levels through the laying cycle which could generate variation in sequence-specific patterns of yolk hormone levels even if these primarily reflect circulating steroid levels.     

重组bFGF滴眼液联合杞菊地黄丸对绝经后干眼症女性血清与泪液中 MMP-2及性激素水平的影响

目的:探讨重组b FGF滴眼液联合杞菊地黄丸对绝经后干眼症女性血清与泪液中MMP-2及性激素水平的影响。方法:收集我院收治的绝经后干眼症女性患者76例,随机分为对照组和实验组,每组38例。对照组患者给予重组牛碱性成纤维细胞生长因子滴眼液治疗,实验组在对照组基础上给予杞菊地黄丸治疗。观察并比较两组患者治疗前后血清以及泪液中E2、MMP-2水平。结果:与治疗前相比,两组患者治疗后血清以及泪液中E2水平均升高,而MMP-2水平均下降,差异具有统计学意义(P0.05);与对照组相比,实验组患者治疗后血清以及泪液中E2水平较高,而MMP-2水平较低,差异具有统计学意义(P0.05)。结论:重组b FGF滴眼液联合杞菊地黄丸能够升高绝经后干眼症女性血清与泪液中E2水平,降低MMP-2水平,对临床具有指导意义。     

CCR2-positive monocytes recruited to inflamed lungs downregulate local CCL2 chemokine levels

The CC chemokine ligand-2 (CCL2) and its receptor CCR2 are essential for monocyte trafficking under inflammatory conditions. However, the mechanisms that determine the intensity and duration of alveolar monocyte accumulation in response to CCL2 gradients in inflamed lungs have not been resolved. To determine the potential role of CCR2-expressing monocytes in regulating alveolar CCL2 levels, we compared leukocyte recruitment kinetics and alveolar CCL2 levels in wild-type and CCR2-deficient mice in response to intratracheal LPS challenge. In wild-type mice, LPS elicited a dose- and time-dependent alveolar monocyte accumulation accompanied by low CCL2 levels in bronchoalveolar lavage fluid (BALF). In contrast, LPS-treated CCR2-deficient mice lacked alveolar monocyte accumulation, which was accompanied by relatively high CCL2 levels in BALF. Similarly, wild-type mice that were treated systemically with the blocking anti-CCR2 antibody MC21 completely lacked LPS-induced alveolar monocyte trafficking that was associated with high CCL2 levels in BALF. Intratracheal application of anti-CCR2 antibody MC21 to locally block CCR2 on both resident and recruited cells did not affect LPS-induced alveolar monocyte trafficking but led to significantly increased BALF CCL2 levels. Reciprocally bone marrow-transplanted, LPS-treated wild-type and CCR2-deficient mice showed a strict inverse relationship between alveolar monocyte recruitment and BALF CCL2 levels. In addition, freshly isolated human and mouse monocytes were capable of integrating CCL2 in vitro. LPS-induced alveolar monocyte accumulation is accompanied by monocytic CCR2-dependent consumption of CCL2 levels in the lung. This feedback loop may limit the intensity of monocyte recruitment to inflamed lungs and play a role in the maintenance of homeostasis.     

Human microvascular endothelial cell prostaglandin E1 synthesis during in vitro ischemia-reperfusion

Ischemia-reperfusion injury is a microvascular event documented in numerous in vivo animal models. In animal models, prostaglandin and prostaglandin analogues have been found to ameliorate reperfusion injury. These studies were undertaken to evaluate human microvascular endothelial PGE(1) synthesis during in vitro ischemia followed by reperfusion. Human (neonatal) microvascular endothelial cell (MEC) cultures (n = 6) were subjected to sequential 2 h periods of normoxia (20% O(2)), ischemia (1.5% O(2)), and reperfusion (20% O(2)). Prostaglandin E(2) synthesis in conditioned media was determined by ELISA. Steady state levels of MEC prostaglandin H synthase (PGHS)-1 and -2 mRNA were assessed at the end of each 2-h period using RT-PCR and a quantitative mRNA ELISA. MEC PGHS protein levels were analyzed using an ELISA. PGE(1) release increased significantly during the initial 30 min of ischemia, but rapidly fell below normoxic levels by 90 and 120 min. During reperfusion, PGE(1) release returned to normoxic levels at 30, 60, and 90 min, and exceeded normoxic levels at 120 min. PGHS-1 mRNA levels were undetectable during all experimental conditions. PGHS-2 mRNA levels were unchanged by ischemia, but were decreased by reperfusion. In contrast, PGHS-2 protein levels increased 3-fold during ischemia, and remained elevated during reperfusion. Human MEC do not express PGHS-1 mRNA in vitro. Prolonged ischemia decreases MEC PGE(1) synthesis, and stimulates increased PGHS-2 protein levels without altering the steady state levels of COX-2 mRNA. During reperfusion, increased PGHS-2 protein levels persist and are associated with stimulated PGE(2) secretion, despite relative decreases in PGHS-2 mRNA.     

Measurement of normative HDL subfraction cholesterol levels by Gaussian summation analysis of gradient gels

This report describes development of a computerized method for analyzing polyacrylamide gradient gels of high density lipoproteins (HDL) by Gaussian summation, a simple technique to obtain standardized measurements of size and amount of HDL subfractions. Conditions for reproducibility and ranges of linearity were established. By Gaussian summation analysis, five or six HDL subfractions could be found in the plasma of most normolipidemic people. The relationship of staining intensity to cholesterol level was determined for Coomassie Blue R-250, permitting determination of the cholesterol levels in the individual subfractions, with standard errors of repeated measurements of 2% or less of the total HDL area, and accuracy, limited by the standard error of the chromogenicity, of 1-2 mg/dl for the least abundant fractions and 3-4 mg/dl for the most abundant subfractions. Levels of HDL2b measured by this method were statistically the same as levels of HDL2 measured by dextran sulfate-Mg2+ precipitation. Gaussian summation analysis of gradient gels was used to measure HDL subfraction cholesterol levels in subjects from the Baltimore Longitudinal Study on Aging to obtain normative levels for men and women for the major HDL subfractions. Comparisons of these levels with each other and with triglyceride and cholesterol levels showed that triglyceride levels were inversely correlated with levels of HDL2a and HDL2b, cholesterol levels were directly correlated with levels of HDL3b and HDL3a, and that HDL3b levels were inversely correlated with levels of both HDL2a and HDL2b.     

Estradiol increases somatomedin-C concentrations in adolescent rhesus macaques (Macaca mulatta)

Estradiol (E2) may enhance somatomedin-C (Sm-C) secretion during puberty in female rhesus monkeys. The present study evaluated the importance of age and acute changes in E2 on Sm-C secretion. Intact (INT) females at their first ovulation (age 3.5 yr; n = 6) had higher levels of Sm-C across the ovulatory cycle than did intact adults (ADT) (n = 5). Levels of Sm-C were similar for both groups during the follicular and luteal phases despite higher follicular phase levels of E2. Young, ovariectomized, E2-treated (E2OVX) females (age 3.5 yr; n = 5; E2 = 50 pg/ml) had higher basal levels of Sm-C than did either age-matched ovariectomized (OVX) females (n = 3), ovariectomized adults (OXA), or E2-treated ovariectomized adults (E2A) (E2 = 100 pg/ml). When ovariectomized groups were given E2 to induce ovulatory increases, no changes in serum Sm-C occurred. Comparisons among age-mates revealed that basal levels of Sm-C were similar between INT and E2OVX, yet these levels were higher than those for OVX. Sm-C levels were similar among all adult groups. Serum growth hormone (GH) was highest in E2OVX, next highest in INT and OVX, and lowest in all adults. Higher Sm-C levels in young animals are, thus, related to these age differences in GH concentrations and are further enhanced by basal levels of E2 and not by acute changes in this steroid. Low Sm-C secretion in adults is associated with low GH levels. Thus, the facilitory effect of basal E2 on Sm-C release is observed during conditions when basal GH levels are elevated, a situation normally limited to adolescence.     

Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-cholesterol levels in type 2 diabetes

Low levels of high-density lipoprotein (HDL)-cholesterol represent an independent cardiovascular risk factor and, besides reduced physical activity, mechanisms leading to decreased HDL-cholesterol levels are not known. We aimed to test the hypothesis, that adiponectin provides a missing link between type 2 diabetes and low levels of HDL-cholesterol, independent from common metabolic risk factors. 523 patients with type 2 diabetes were investigated for adiponectin serum levels and parameters of lipid metabolism. Even after correction for age, gender, BMI and fasting insulin concentration, serum levels of adiponectin were highly significant (P<0.0001) and positively (regression analysis: r=0.86) associated with HDL-cholesterol levels in type 2 diabetes. CONCLUSION: adiponectin seems to predict HDL-cholesterol levels in patients with diabetes mellitus type 2. Low levels of adiponectin are associated with low levels of HDL-cholesterol independently from common metabolic risk factors and therefore represent an independent cardiovascular risk factor in type 2 diabetes. Thus, adiponectin is a potentially new drug target in the treatment of dyslipidaemia.     

Olfactory preferences of Popillia japonica, Vanessa cardui, and Aphis glycines for Glycine max grown under elevated CO2

Levels of atmospheric CO(2) have been increasing steadily over the last century and are projected to increase even more dramatically in the future. Soybeans (Glycine max L.) grown under elevated levels of CO(2) have larger herbivore populations than soybeans grown under ambient levels of CO(2). Increased abundance could reflect the fact that these herbivores are drawn in by increased amounts of volatiles or changes in the composition of volatiles released by plants grown under elevated CO(2) conditions. To determine impacts of elevated CO(2) on olfactory preferences, Japanese beetles (Popillia japonica Newman) and soybean aphids (Aphis glycines Matsumura) were placed in Y-tube olfactometers with a choice between ambient levels of CO(2) gas versus elevated levels of CO(2) gas or damaged and undamaged leaves and plants grown under ambient levels of CO(2) versus damaged and undamaged plants grown under elevated levels of CO(2). All plants had been grown from seeds under ambient or elevated levels of CO(2). Painted lady butterflies (Vanessa cardui L.) were placed in an oviposition chamber with a choice between plants grown under ambient and elevated levels of CO(2). A. glycines and V. cardui showed no significant preference for plants in either treatment. P. japonica showed no significant preference between ambient levels and elevated levels of CO(2) gas. There was a significant P. japonica preference for damaged plants grown under ambient CO(2) versus undamaged plants but no preference for damaged plants grown under elevated CO(2) versus undamaged plants. P. japonica also preferred damaged plants grown under elevated levels of CO(2) versus damaged plants grown under ambient levels of CO(2). This lack of preference for damaged plants grown under elevated CO(2) versus undamaged plants could be the result of the identical elevated levels of a green leaf volatile (2-hexenal) present in all foliage grown under elevated CO(2) regardless of damage status. Green leaf volatiles are typically released from damaged leaves and are used as kairomones by many herbivorous insects for host plant location. An increase in production of volatiles in soybeans grown under elevated CO(2) conditions may lead to larger herbivore outbreaks in the future.     

Predominance of CK2α over CK2α′ in the mammalian brain

CK2 is a heterotetrameric ubiquitous kinase consisting of two catalytic subunits and two regulatory subunits. The two catalytic subunits, α and α', are highly homologous but differ in their C-terminal regions. It is not known whether CK2α and α' have distinctive substrate specificity, since no α- or α'-specific substrate has been identified. Thus, it is assumed that the two kinase isoforms overlap in their substrate specificity. CK2 protein levels and activity were found to be elevated in the brain when compared to other organs. Here we have studied the protein levels of CK2α and α' isoforms in nine major brain regions. We found that both, CK2α and α', are expressed in all brain regions tested. Whereas CK2α levels do not vary strongly across the regions, CK2α' levels are slightly higher in the cortex and hippocampus than in other regions. Furthermore, we show that CK2α protein levels in the striatum are relatively high when compared to CK2α'. The approximate stoichiometry ratio of CK2α:CK2α' is 8:1. Therefore, one can consider that CK2α levels are predominant in comparison to CK2α' levels throughout the mammalian brain.     

Serum beta 2 microglobulin in adult myeloid acute leukemias

Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses.     

Elevated cAMP level attenuates 2-deoxy-d-ribose-induced oxidative damage in pancreatic beta-cells

Glucose toxicity to pancreatic beta-cells is defined as irreversible beta-cell damage, including apoptosis, caused by chronic exposure to high glucose levels in type 2 diabetes. Oxidative stress is an important mechanism for glucose toxicity to pancreatic beta-cells. Reducing sugars produce reactive oxygen species through autoxidation and protein glycosylation. 2-Deoxy-d-ribose (dRib) is a reducing sugar with high reactivity. We investigated whether cAMP-stimulating agents could protect beta-cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24 h. We measured cell survival, intracellular cAMP and H2O2 levels, and apoptosis. dRib decreased cell survival in a dose- and time-dependent manner and markedly increased intracellular H2O2 levels and apoptosis. N-Acetyl-l-cysteine decreased dRib-induced rises in intracellular H2O2 and apoptosis to control levels. Forskolin, IBMX, and dbcAMP markedly elevated intracellular cAMP levels and significantly attenuated dRib-induced cytotoxicity and apoptosis, but had no influence on the dRib-induced rise in intracellular H2O2 levels. These results demonstrate that dRib produced oxidative stress and apoptosis in pancreatic beta-cells and that elevated intracellular cAMP levels reduced dRib-induced damage, independent of reactive oxygen species metabolism.     

Distribution of cyclooxygenase products with cyclooxygenase inhibition in isolated dog lung

Arachidonic acid metabolism can lead to synthesis of cyclooxygenase products in the lung as indicated by measurement of such products in the perfusate of isolated lungs perfused with a salt solution. However, a reduction in levels of cyclooxygenase products in the perfusate may not accurately reflect the inhibition of levels of such products as measured in lung parenchyma. We infused sodium arachidonate into the pulmonary circulation of isolated dog lungs perfused with a salt solution and measured parenchymal, as well as perfusate, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), and thromboxane B2 (TxB2). These studies were repeated with indomethacin (a cyclooxygenase enzyme inhibitor) in the perfusate. We found that indomethacin leads to a marked reduction in perfusate levels of PGF2 alpha, PGE2, 6-keto-PGF1 alpha, and TxB2, as well as a marked reduction in parenchymal levels of 6-keto-PGF1 alpha and TxB2 when parenchymal levels of PGF2 alpha and PGE2 are not reduced. We conclude that, with some cyclooxygenase products, a reduction in levels of these products in the perfusate of isolated lungs may not indicate inhibition of levels of these products in the lung parenchyma and that a reduction in one parenchymal product may not predict the reduction of other parenchymal products. It can be speculated that some of the physiological actions of indomethacin in isolated lungs may result from incomplete or selective inhibition of synthesis of pulmonary cyclooxygenase products.     

miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle

Although aberrant miRNA signatures are associated with diabetes, yet, the status and role of altered miRNAs in the diabetic skeletal muscle is currently poorly understood. Here, we report that 41 miRNAs are altered in the diabetic gastrocnemius skeletal muscle and of these, miR-135a that is identified as a critical regulator of myogenesis, is significantly up-regulated. IRS2 is predicted as its potential putative target and its levels are down-regulated in the diabetic gastrocnemius skeletal muscle. In C2C12 cells, while miR-135a levels decreased during differentiation, IRS2 levels were up-regulated. miR-135a significantly reduced IRS2 protein levels and its 3′UTR luciferase reporter activity and these were blunted by the miR-135a inhibitor and mutation in the miR-135a binding site. Knock-down of endogenous miR-135a levels increased IRS2 at the mRNA and protein levels. miR-135a also attenuated insulin stimulated phosphorylation and activation of PI3Kp85α and Akt and glucose uptake. miR-135a levels were also found to be elevated in the human diabetic skeletal muscle. In-vivo silencing of miR-135a alleviated hyperglycemia, improved glucose tolerance and significantly restored the levels of IRS2 and p-Akt in the gastrocnemius skeletal muscle of db/db mice without any effect on their hepatic levels. These suggest that miR-135a targets IRS2 levels by binding to its 3′UTR and this interaction regulates skeletal muscle insulin signaling.     

Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV

Serum levels of soluble IL-2R (sIL-2R) were measured in blood donors seropositive for HIV. Approximately one-half (53/101) of these seropositive donors exhibited increased serum sIL-2R levels compared with seronegative controls (n = 65). Further, a significant inverse correlation was observed between serum sIL-2R levels and CD4 cell levels in seropositive study participants. These findings suggest that increased serum sIL-2R levels in HIV infection may be linked to CD4 cell loss, and thus reflective of the stage of HIV-induced disease.