Fine mapping of a QTL and identification of candidate genes associated with cold tolerance during germination in peanut (Arachis hypogaea L.) on chromosome B09 using whole genome re-sequencing.

Low temperatures significantly affect the growth and yield of peanuts. Temperatures lower than 12 °C are generally detrimental for the germination of peanuts. To date, there has been no report on precise information on the quantitative trait loci (QTL) for cold tolerance during the germination in peanuts. In this study, we developed a recombinant inbred line (RIL) population comprising 807 RILs by tolerant and sensitive parents. Phenotypic frequencies of germination rate low-temperature conditions among RIL population showed normally distributed in five environments. Then, we constructed a high density SNP-based genetic linkage map through whole genome re-sequencing (WGRS) technique and identified a major quantitative trait locus (QTL), qRGRB09, on chromosome B09. The cold tolerance-related QTLs were repeatedly detected in all five environments, and the genetic distance was 6.01 cM (46.74 cM - 61.75 cM) after taking a union set. To further confirm that qRGRB09 was located on chromosome B09, we developed Kompetitive Allele Specific PCR (KASP) markers for the corresponding QTL regions. A regional QTL mapping analysis, which was conducted after taking the intersection of QTL intervals of all environments into account, confirmed that qRGRB09 was between the KASP markers, G22096 and G220967 (chrB09:155637831-155854093), and this region was 216.26 kb in size, wherein a total of 15 annotated genes were detected. This study illustrates the relevance of WGRS-based genetic maps for QTL mapping and KASP genotyping that facilitated QTL fine mapping of peanuts. The results of our study also provided useful information on the genetic architecture underlying cold tolerance during germination in peanuts, which in turn may be useful for those engaged in molecular studies as well as crop improvement in the cold-stressed environment.

Metal-organic gel templated synthesis of magnetic porous carbon for highly efficient removal of organic dyes.

Magnetic porous carbon composites are promising materials in various applications, such as adsorbents, supercapacitors and catalyst supports, due to their high surface area, thermal and chemical stability, and easy separation. However, despite the increasing number of reports of magnetic porous carbon composites, the preparation of these materials with environmentally friendly procedures still remains a great challenge. Herein, we report a facile method to prepare a magnetic porous carbon composite with high surface area from a Fe-based metal-organic gel (MOG) template, an extended structure of a metal-organic framework (MOF). The obtained magnetic porous carbon composite was applied to remove organic dyes from an aqueous solution by selecting methyl orange (MO) as a model molecule. It exhibits excellent adsorption capacity (182.82 mg g(-1)), fast adsorption kinetics (8.13 × 10(-3) g mg(-1) min(-1)), and a perfect magnetic separation performance for the MO removal. This study demonstrates a new way to achieve clean synthesis of magnetic porous carbon materials, and opens a new door for the application of MOGs in organic dye removal.

An efficient room temperature core-shell AgPd@MOF catalyst for hydrogen production from formic acid.

Novel core-shell AgPd@MIL-100(Fe) NPs were fabricated by a facile one-pot method. Significantly, the as-prepared core-shell NPs exhibit much higher catalytic activity than the pure AgPd NPs toward hydrogen production from formic acid without using any additive at room temperature.

Multifunctional Au-Fe3O4@MOF core-shell nanocomposite catalysts with controllable reactivity and magnetic recyclability.

The recovery and reuse of expensive catalysts are important in both heterogeneous and homogeneous catalysis due to economic and environmental reasons. This work reports a novel multifunctional magnetic core-shell gold catalyst which can be easily prepared and shows remarkable catalytic properties in the reduction of 4-nitrophenol. The novel Au-Fe3O4@metal-organic framework (MOF) catalyst consists of a superparamagnetic Au-Fe3O4 core and a porous MOF shell with controllable thickness. Small Au nanoparticles (NPs) of 3-5 nm are mainly sandwiched between the Fe3O4 core and the porous MOF shell. Catalytic studies show that the core-shell structured Au-Fe3O4@MOF catalyst has a much higher catalytic activity than other reported Au-based catalysts toward the reduction of 4-nitrophenol. Moreover, this catalyst can be easily recycled due to the presence of the superparamagnetic core. Therefore, compared to conventional catalysts used in the reduction of 4-nitrophenol, this porous MOF-based magnetic catalyst is green, cheap and promising for industrial applications.

Inhibition of the connexin 43 elevation may be involved in the neuroprotective activity of leptin against brain ischemic injury.

Leptin is a multifunctional hormone produced by the ob gene and is secreted by adipocytes that regulate food intake and energy metabolism. Numerous studies demonstrated that leptin is a novel neuroprotective effector, however, the mechanisms are largely unknown. Herein, we demonstrate the protective activities of leptin after ischemic stroke and provide the first evidence for the involvement of the connexin 43 (Cx43) in leptin-mediated neuroprotection. We found that leptin treatment reduces the infarct volume, improves animal behavioral parameters, and inhibits the elevation of Cx43 expression in vivo. In vitro, leptin reverses ischemia-induced SY5Y and U87 cells Cx43 elevation, secreted glutamate levels in medium and SY5Y cell death, these roles could be abolished by leptin receptor blocker. Additionally, leptin administration upregulated the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. Moreover, ERK1/2 inhibitors pretreatment reversed the effects of leptin on Cx43 expression, glutamate levels and cell apoptosis. In conclusion, the present study demonstrated that leptin can reduce the Cx43 expression and cell death both in vivo and in vitro via ERK1/2 signaling pathway. This result provides a novel regulatory signaling pathway of the neuroprotective effects of leptin and may contribute to ischemic brain injury prevention and therapy.

Diagnostic value of serum leptin and a promising novel diagnostic model for sepsis.

Diagnosis of sepsis in critically ill patients is important to reduce morbidity and mortality. The present study was conducted to determine the role of serum leptin in the early diagnosis of sepsis and to establish a diagnostic model for sepsis. A retrospective study was conducted of 331 patients from an intensive care unit. All patients underwent consistent blood collection at 6:00 a.m. every morning after fasting. Serum leptin concentrations and additional markers of sepsis were compared between the sepsis group (n=128) and the non-sepsis group (n=203). Septic patients displayed significantly higher leptin serum concentrations compared with those of the non-sepsis group (mean concentration, 11.67 versus 4.824 mg/dl; P<0.001). The leptin levels in male patients were higher than those in female patients, particularly in the sepsis group. The accuracy of serum leptin levels in distinguishing septic patients from non-septic patients was 76%, and the area under the receiver operating characteristic (ROC) curve of serum leptin was ≤0.8. Additional markers of inflammation in the sepsis group were also significantly higher than those in the non-sepsis group. Positive correlations were identified between leptin and body temperature, heart rate and creatinine levels. Therefore, a prognostic model comprising a combination of leptin with temperature, platelet count, white blood cell count and heart rate was evaluated as an effective logistic regression model for the diagnosis of sepsis. The logistic regression output cut-off value was 0.46 and the area under the ROC curve was 0.953 (P<0.0001). It may be concluded that leptin is a valuable marker in the diagnosis of sepsis and the proposed prognostic model is an effective logistic regression model for the diagnosis of sepsis. The prognostic model is able to aid the differentiation of septic patients from non-septic patients.

Localized leptin release may be an important mechanism of curcumin action after acute ischemic injuries.

BACKGROUND: Previous studies have demonstrated that both curcumin and leptin are protective factors against acute injuries. Here, we investigated whether leptin and its signaling pathway mediate the protective effects of curcumin. METHODS: A solid dispersion of curcumin-polyvinylpyrrolidone K30 was prepared and administered intraperitoneally. In vivo intestinal ischemia/reperfusion (I/R) injury in mice determined the effects of curcumin administration on inflammation, oxygen radical production, and leptin expression. In vitro studies using the venous epithelial cell line ECV-304 examined hypoxia/reoxygenation-induced leptin expression and release after curcumin administration. Furthermore, the effects on the leptin-regulated ERK1/2 and p38 MAPK signaling pathways were also explored. RESULTS: Intestinal I/R induced marked bowel injuries. Curcumin treatment significantly improved animal survival and reduced the pathologic injuries in the intestines. Furthermore, the elevated intestinal water content and levels of malondialdehyde, interleukin 1ß (IL-1ß) and IL-6 were significantly decreased, but levels of superoxide dismutase increased. Interestingly, we found that the decreased leptin and its receptor Ob-Rb were restored by curcumin administration. In addition, in vitro studies showed that curcumin increased leptin expression and release after hypoxia/reoxygenation-induced cell injuries. Moreover, curcumin treatment restored decreased ERK1/2 phosphorylation (p-ERK1/2) and inhibited overactive p38 (p-p38) after injuries, and the effect was reversed by a leptin-specific antibody or Ob-R blocker. CONCLUSION: These data suggest that leptin and Ob-Rb-dependent ERK and p38 MAPK signaling pathways may be involved in curcumin protection against intestinal I/R injury, and leptin may be a potential target of curcumin in intestinal I/R injury and other related acute diseases.

Leptin attenuates cerebral ischemia injury through the promotion of energy metabolism via the PI3K/Akt pathway.

The purpose of this study was to investigate the protective mechanism of leptin-mediated metabolic recovery against cerebral injury after ischemia and reperfusion. We determined the neurologic deficit score, extent of brain edema, and infarct volume after reperfusion. The histopathologic alterations and changes in glucose uptake in the brain were also observed. Moreover, the levels of lactate dehydrogenase (LDH), lactic acid, pyruvate, and ATP in brain tissue were detected. Leptin levels in serum were also detected. To further define leptin-induced neuroprotective signaling pathways, we examined the levels of phosphorylated Akt (p-Akt) in the brain and in cultured cells. After transient ischemia, leptin treatment markedly reduced the neurologic deficits, cerebral infarct volume, and brain edema. After leptin injection, ATP, leptin, and p-Akt levels were significantly increased, LDH levels and lactic acid/pyruvate ratio were noticeably reduced, and histopathologic injuries were alleviated, which were all reversed by the PI(3)K inhibitor LY294002. These data show that leptin ameliorates cerebral ischemia/reperfusion injury by enhancing p-Akt, which in turn improves the supply of energy. The PI(3)K/Akt pathway was found to be the critical pathway for the mediation of leptin-induced neuroprotection, a finding that may prove to be useful in the treatment of ischemic stroke.

Leptin administration alleviates ischemic brain injury in mice by reducing oxidative stress and subsequent neuronal apoptosis.

BACKGROUND: Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model. METHODS: The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/leukemia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay. RESULTS: Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury. CONCLUSIONS: Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.

Leptin relieves intestinal ischemia/reperfusion injury by promoting ERK1/2 phosphorylation and the NO signaling pathway.

BACKGROUND: Recently, research has indicated that leptin plays a protective role in traumatic brain and liver injury. We studied the protective effect of leptin on intestinal I/R injury and examined its mechanism by using mice intestinal I/R model and murine peritoneal macrophage hypoxia/reoxygenation (H/R) injury model. METHODS: Leptin was intraperitoneally administrated at 45 minutes after ischemia, then reperfusion for two hours. Cells were treated with different concentrations of leptin at three hours after hypoxia, then reoxygenation for six hours. Mice intestines were harvested for histopathologic properties. The malondialdehyde, nitric oxide (NO), interleukin-6, and total antioxidative capacity were detected according to respective assay kit. Phosphorylated extracellular regulated kinase1/2 (p-ERK1/2) and phosphorylated cytosolic phospholipase A(2) (p-cPLA2) were determined by Western blot assay. RESULTS: Here, we show that leptin reduced intestinal histologic alterations, malondialdehyde and interleukin-6 levels but increased the endogenous leptin expression and NO production in the intestines. Leptin also increased the NO and total antioxidative capacity levels in cells. We further demonstrated that leptin markedly activated ERK1/2 in the intestines and activated ERK1/2 and cPLA2 in the cells. Moreover, the protective effect of leptin against intestinal I/R injury and elevated NO production was attenuated by blocking the ERK1/2 pathway. CONCLUSIONS: These data demonstrate that leptin ameliorated intestinal I/R and peritoneal macrophage H/R injury by enhancing ERK1/2 phosphorylation and promoting the NO production signaling pathway.

Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression.

Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1mg/kg in 200 µL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 µg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37) (4 × 10(-8)mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression.

Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury and represents a potential therapeutic target.

AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60'R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

[Orexin-A in hepatic reperfusion-induced liver injury in rats].

OBJECTIVE: To explore the change of orexin-A expression in hepatic reperfusion and their association with liver injury, and to find out the role of orexin-A in traumatic stress responses. METHODS: A 70% hepatic reperfusion model of rats was established, setting groups of sham-operation and injury ones with different reperfusion time. A self-produced radioimmunoassay and relevant kits were used to detect the protein level of orexin-A in the plasma and the hypothalamus, serum glucose, total anti-oxidation capacity and alanine transaminase, HE staining and immunohistochemistry were used to investigate the pathological variation and protein expression of orexin-A in the liver, while RT-PCR was applied to observe mRNA expression of orexin-A in the hypothalamus and the liver. RESULTS: Both the shape of standard curve and metrical results of the self-produced orexin-A radioimmunoassay were good. Protein levels of orexin-A in the plasma and the hypothalamus in each reperfusion group showed no significant change. Serum glucose and total anti-oxidation capacity increased significantly at the later phase of injury. There was significant and positive linear correlation between the plasma orexin-A and serum glucose and total anti-oxidation capacity; serum alanine transaminase in each reperfusion group was significantly higher, and liver damage was significantly alleviated at the later phase of the injury. Different extents of variation were observed in protein expression of orexin-A in the liver and its mRNA expression in the hypothalamus and the liver. CONCLUSION: Orexin-A undergoes significant changes during hepatic reperfusion, indicating that orexin-A participates in the modulation of hepatic reperfusion-induced liver injury and internal disorders.

[Effects of ethyl pyruvate on injuries of sepsis in mice].

OBJECTIVE: To explore the effect of ethyl pyruvate (EP) and alkaline phosphatase (ALP) on injuries of sepsis and the mechanism involved. METHODS: A murine sepsis model of cecal ligation and puncture was reproduced, and 90 male Kunming mice were divided randomly into sham-operation, model and EP-intervention groups. 75 mg/kg EP was intraperitoneally injected in EP groups 1 hour after establishment of model, and the mice in model group were given a same volume of Ringer's solution. The eyeballs were removed in the latter two groups, and mice were sacrificed at 15 minutes and 1, 3 and 6 hours in subgroups of 10 mice each. ALP, uric acid (UA) and ratio of lactic acid and pyruvic acid were determined in serum and homogenized lung tissue by autonomous biochemical analyzer, and pathological changes in intestine were observed by hematoxylin-eosin (HE) staining. RESULTS: Compared with sham-operation group, serum ALP in model groups and EP groups decreased significantly (P<0.05 or P<0.01), and ALP level of EP group was significantly lower than model group at 6 hours after injury (P<0.05). Compared with sham-operation group, serum UA in model group increased significantly at 1 hour, and reached the highest level at 3 hours (both P<0.05) but decreased significantly later. UA in EP group was significantly lower than that in model group at 1 hour and 3 hours (both P<0.05). Lactic acid/pyruvic acid ratio in lung homogenate of EP group was significantly lower than that of the model group at all the time points (all P<0.05). Intestinal structural damages were distinctly improved in EP group compared with model group at 3 hours and 6 hours (both P<0.05 ). CONCLUSION: EP promotes the utilization of serum ALP, decreases serum UA, ameliorates acidosis and intestinal damages, thus exerting a protective effect on sepsis-induced organ injuries.

Heart-type fatty acid-binding protein is a useful marker for organ dysfunction and leptin alleviates sepsis-induced organ injuries by restraining its tissue levels.

Heart-type fatty acid-binding protein (H-FABP) is widely distributed and has been used to diagnose certain diseases. However, its alteration during infection-evoked organ dysfunction, and the potential association between leptin and it in injury or infection has not been investigated. In the current study, serum H-FABP, leptin, C-reactive protein and interleukin-1beta in the patients with pulmonary infection-induced multiple organ dysfunction were detected. Moreover, a mouse model of sepsis was established, and serum alanine transaminase, uric acid, tissue H-FABP, myeloperoxidase, superoxide dismutase activity and histological alterations in lung and intestine were investigated. Serum H-FABP and leptin increased simultaneously and significantly in the patients, and leptin alleviated pulmonary and intestinal injuries by restraining tissue H-FABP secretions in the mouse model of sepsis. Other investigated variables showed different but independent alterations. In conclusion, H-FABP represents a useful diagnostic marker for organ dysfunction, and its association with leptin will be a novel target for emergency aid.

[Role of leptin in hepatic ischemia/reperfusion-induced hepatic injury].

UNLABELLED: OBJECTIVE; To study the changes of leptin after hepatic ischemia/reperfusion (H-I/R) and its effects on H-I/R-induced hepatic injury. METHODS: A 70% H-I/R model of rats was established. The rats were divided into groups with different reperfusion times and sham-operation group. Radioimmunoassay was applied to measure protein levels of leptin in serum and adipose tissues of the rats. Enzyme-colorimetry was used to detect serum alanine transaminase. Hematoxylin-eosin staining and immunohistochemistry were applied to investigate pathological variations and protein expressions of leptin in livers, respectively. RT-PCR was used to detect leptin mRNA expressions in adipose tissues and livers. RESULTS: Compared with the sham-operation group, serum leptin increased significantly in the 60 min ischemia/360 min reperfusion (I60' R360') group; protein level of leptin in adipose tissues increased significantly in the I60'R60' group; serum alanine transaminase increased significantly in all of the four reperfusion groups; protein expressions of leptin in livers increased significantly in the I60'R60' and 160'R240' groups; leptin mRNA expression in adipose tissues decreased significantly in the I60'R150' group; leptin mRNA expression in livers increased significantly in the 160'R60' group; leptin mRNA expressions in livers decreased significantly in the I60'R150', I60'R240' and I60'R360' groups. Pathological investigation showed that hepatic impairments at the early phase of H-I/R were more serious. The impairments at the later phase lessened gradually. CONCLUSION: The change of leptin expressions after H-I/R may be a protective factor to withstand H-I/ R-induced hepatic injury.

[Distribution of leptin expression and its effect on the recovery of sepsis-induced internal disorders].

OBJECTIVE: To explore the distribution of leptin expression and the effect of sepsis on leptin protein and mRNA levels. METHODS: Vital organ samples including hypothalamus, lung, liver, spleen, stomach, duodenum, kidney, epididymal fat pad and testis of normal rats were collected. The mRNA expressions of leptin in those samples were determined by RT-PCR. The sepsis rat model induce by cecal ligation and perforation (CLP) was established, setting groups of sham-operation, CLP model, CLP + intralipid injection, CLP + estradiol injection and CLP + insulin injection, as the latter three groups were set to intervene energy metabolism and neuroendocrine function. Radioimmunoassay was applied to measure serum leptin concentrations in each group at 12 h after injury, while RT-PCR was also used to detect Leptin mRNA expressions in hypothalamus, fat and lung after injury. RESULTS: Leptin mRNA expressions were confirmed in all the above nine vital organs, with the highest in kidney but the lowest in testis. The serum leptin level showed no significant difference between sham operation group and other four groups. Compared with sham operation group, the Leptin mRNA level in CLP group decreased significantly in hypothalamus, fat and lung, while that in the other three groups showed different changes. The effect of intralipid on Leptin mRNA expression was found to be a dual-direction pattern, with central stimulation but peripheral inhibition. CONCLUSION: Leptin is widely expressed in multiple vital organs, and it may be a protective factor to promote recovery of sepsis-induced internal disorders.

p38 kinase/cytosolic phospholipase A2/cyclooxygenase-2 pathway: a new signaling cascade for lipopolysaccharide-induced interleukin-1beta and interleukin-6 release in differentiated U937 cells.

p38 Mitogen-activated protein kinase (p38 MAPK) activation is essential for lipopolysaccharide (LPS)-induced pro-inflammatory cytokines expression. Although the regulation results from combined effect of both transcription and translation levels, the precise mechanism by which p38 regulates still remains to be elucidated. Our previous work showed cytosolic phospholipase A(2) (cPLA(2)), a substrate of p38, was involved in this regulation. Further investigations were carried out to study the possible mechanisms of the interleukin expression modulated by cPLA(2) in LPS-treated differentiated U937 cells. p38 MAPK inhibitor SB203580 suppressed interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) release, as well as the activation of cPLA(2). Transfection of cPLA(2) antisense oligonucleotides or pre-treatment with cPLA(2) inhibitor AACOCF3 abolished IL-1beta and IL-6 release in a dose-dependent manner. These implied a potential role of cPLA(2) in LPS-induced p38 pathways on interleukin release. As a downstream enzyme of cPLA(2), cyclooxygenase-2 (COX-2) was down-regulated by SB203580 and/or AACOCF(3), which precisely matched the levels of IL-1beta and IL-6. Treatment with the COX-2 inhibitor (NS-398) or COX-2 antisense oligonucleotides also diminished IL-1beta and IL-6 release. Given these findings, the p38 MAPK/cPLA(2)/COX-2 pathway was proposed to be implicated in the LPS-induced IL-1beta and interleukin-6 production in differentiated U937 cells.

[Effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs of rats].

AIM: To explore the effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs, and find out the role leptin plays in acute inflammation. METHODS: A cecal ligation and perforation model of rats was established, setting groups of sham-operation, intralipid injection, injury, estradiol injection and insulin injection. A rat leptin radioimmunoassay was used to check serum leptin concentrations at 12 h after the injury, and RT-PCR was also used to detect leptin mRNA expressions in adipose tissue, lung and liver. RESULTS: Compared with serum leptin level of sham-operation group after injury, that of all the other four groups showed no significant difference, while the level of intralipid group was significantly higher than that of injury group and estradiol group. Compared with leptin mRNA expression level of sham-operation group after injury, that of the other four groups had different changes. Leptin mRNA expression of intralipid group was significantly increased in adipose tissue but decreased in lung and liver. CONCLUSION: Leptin expression levels may be affected by the changes of energy metabolism and neuroendocrine function after injury, which suggests a possible protective role for leptin in the recovery of body homeostasis.

Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin.

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.