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Springer Nature Switzerland AG

Springer Nature Switzerland AG

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/ CB1R system. Here we show that pharmacological activation/blockade and genetic overexpression/ deletion of hepatic CB1 R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB1 R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C/EBP homologous protein (CHOP), whereas direct activation of CB1 R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB/CB1R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP. © 2020, eLife Sciences Publications Ltd. All rights reserved.

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/ CB1R system. Here we show that pharmacological activation/blockade and genetic overexpression/ deletion of hepatic CB1 R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB1 R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C/EBP homologous protein (CHOP), whereas direct activation of CB1 R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB/CB1R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP.

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/CB(1)R system. Here we show that pharmacological activation/blockade and genetic overexpression/deletion of hepatic CB(1)R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB(1)R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C/EBP homologous protein (CHOP), whereas direct activation of CB(1)R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB/CB(1)R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP.

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/CB(1)R system. Here we show that pharmacological activation/blockade and genetic overexpression/deletion of hepatic CB(1)R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB(1)R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C/EBP homologous protein (CHOP), whereas direct activation of CB(1)R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB/CB(1)R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP.

Patent No.

Australia    2640999
Canada    2641008
China    2641013
EP    2641020
Japan    2641036
Mexico    2641049
New Zealand    2641055
Korea    2641060
USA    2641078 , 2641559

Snake venoms could lead to the development of new drugs to treat a range of life-threatening conditions like cardiovascular diseases. Most snake venoms contain a large variety of lethal toxins as well as anti-adhesive proteins such as disintegrins, which have evolved from the harmless compounds ADAMs (proteins with a disintegrin and a metalloprotease domain) and C-type lectin proteins which disturb connective tissue and cell-matrix interaction. These anti-adhesive proteins target and block integrin receptors and disrupt normal biological processes in snakes' prey such as connective tissue physiology and blood clotting. This chapter provides the experimental details of a practical, cell-based adhesion protocol to help identify and isolate disintegrins and C-type lectin proteins from snake venoms, important tools in integrin research and lead compounds for drug discovery.

A ubiquitous way that cells share information is by exchanging molecules. Yet, the fundamental ways that this information exchange is influenced by intracellular dynamics remain unclear. Here we use information theory to investigate a simple model of two interacting cells with internal feedback. We show that cell-to-cell molecule exchange induces a collective two-cell critical point and that the mutual information between the cells peaks at this critical point. Information can remain large far from the critical point on a manifold of cellular states but scales logarithmically with the correlation time of the system, resulting in an information-correlation time trade-off. This trade-off is strictly imposed, suggesting the correlation time as a proxy for the mutual information.

Like most insects, those that feed on both prey and plant materials harbor symbiotic bacteria in their body. Yet the involvement of bacteria in the feeding habits of these omnivorous consumers has yet to be investigated. In the present study, we took the first step toward testing the hypothesis that bacterial symbionts are involved in the feeding habits of the omnivorous bugMacrolophus pygmaeus. We (I) characterized the microbiome (the assembly of bacteria and fungi) ofM. pygmaeus, and (II) determined the identity and location of the most dominant bacteria species within the host body. We found thatM. pygmaeusmicrobiome is dominated by twoRickettsiaspecies,R. belliandR. limoniae. These bacteria are found in high numbers in the digestive system of the bug, each exhibiting a unique distribution pattern, and for the most part, do not share the same cells in the gut. These results strongly suggest that the host bug may gain some nutritional benefits by hosting the two dominant symbiotic bacteria in its gut. Bacterial symbionts in arthropods are common, vary in their effects, and can dramatically influence the outcome of biological control efforts.Macrolophus pygmaeus(Heteroptera: Miridae), a key component of biological control programs, is mainly predaceous but may also display phytophagy.M. pygmaeushosts symbioticWolbachia, which induce cytoplasmic incompatibility, and twoRickettsiaspecies,R. belliiandR. limoniae, which are found in all individuals tested. To test possible involvement of the twoRickettsiaspecies in the feeding habits ofM. pygmaeus, we first showed that the microbiome of the insect is dominated by these three symbionts, and later described the distribution pattern of the twoRickettsiaspecies in its digestive system. Although bothRickettsiaspecies were located in certain gut bacteriocyes, in caeca and in Malpighian tubules of both sexes, each species has a unique cellular occupancy pattern and specific distribution along digestive system compartments. Infrequently, both species were found in a cell. In females, bothRickettsiaspecies were detected in the germarium, the apical end of the ovarioles within the ovaries, but not in oocytes. Although the cause for theseRickettsiadistribution patterns is yet unknown, it is likely linked to host nutrition while feeding on prey or plants.

Privacy and energy-saving are key functionalities for next-generation smart windows, while to achieve them independently on a window is challenging. Inspired by the cephalopod skin, we have developed a versatile thermo- and mechano-chromic design to overcome such challenge and reveal the mechanism via both experiments and simulations. The design is facile with good scalability, consisted of well-dispersed vanadium dioxide (VO2) nanoparticles (NPs) with temperature-dependent localized surface plasmon resonance (LSPR) in transparent elastomers with dynamic micro wrinkles. While maintaining a fixed solar energy modulation of (ΔTsol), the design can dynamically control visible transmittance (Tvib) from 60% to 17%, adding a new dimension to VO2-based smart windows. We prove that the optical modulation relies on the microtexture-induced broadband diffraction and the plasmon-enhanced near-infrared absorbance of VO2 NPs. We further present a series of modified designs towards additional functionalities. This work opens an avenue for independent dual-mode windows and it may inspire development from fundamental material, optic, and mechanical science to energy-related applications.

Bezafibrate (BzF) is eliminated by renal excretion and dosage must be reduced in patients with chronic kidney disease (CKD). There is a concern that BzF causes a further deterioration in renal function in patients with CKD. This study assessed whether BzF discontinuation or dose reduction in CKD patients improves renal function. 117 CKD patients treated with BzF between 2009 and 2014 were studied for demographics, comorbid conditions and laboratory variables. Data compared 2 groups: an intervention group of 64 patients where recommendations regarding BzF administration was implemented and a control group of 37 patients. Follow-up was maintained for 12 months. In the intervention group, estimated glomerular filtration rate (eGFR) increased from 38 to 42 mL/min/1.73 m(2) (p = 0.01); blood urea levels decreased from 81 to 77 mg/dL (p = 0.04). Serum creatinine decreased by more than 0.2 mg/dL in 45% of the intervention group, as compared to 19% of the control group (p < 0.01). Improvement in eGFR was seen exclusively in patients who stopped BzF completely (eGFR increased from 38 to 44 mL/min/1.73 m(2)). In the intervention group, TG level increased from 183 to 220 mg/dL (p < 0.001). BzF cessation in approximately 50% of patients with CKD was associated with an increase in eGFR.