Hypothalamic FTO promotes high-fat diet-induced leptin resistance in mice through increasing CX3CL1 expression.

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity.

Effect of granular activated carbon on the aerobic granulation of sludge and its mechanism.

The granulation of activated sludge and effect of granular activated carbon (GAC) was investigated under the alternative anaerobic and aerobic conditions. The results showed that GAC accelerated the granulation, but had no obvious effect on the bacterial community structure of granules. The whole granulation process could be categorized into three phases, i.e. lag, granulation and granule maturation phase. During lag period GAC provided nuclei for sludge to attach, and thus enhanced the morphological regularization of sludge. During granulation period the granule size increased significantly due to the growth of bacteria in granules. GAC reduced the compression caused by the inter-particle collisions and thus accelerate the granulation. GAC has no negative effect on the performance of SBR, and thus efficient simultaneous removal of COD, nitrogen and phosphorus were obtained during most of the operating time.

Primary study of skin wound healing in rats for Loropetalum chinens / 中国中药杂志

<p><b>OBJECTIVE</b>Cutaneous wound is a common health problem of humans. Loropetalum chinens, a medicinal plant, is widely used to treat wounds among the people. The research aims to observe whether L. chinens can promote the rats' wounds healing process, isolate the extracts primarily and commit the wound healing selection, which provide work basis for wound healing research of L. chinens.</p><p><b>METHOD</b>First we analyzed the possible components with HC-MS/MS, then committed our wound healing experiments for L. chinens in the rat incision wound model and excision wound model, which are commonly used worldwide. After that, we carried on the preliminary isolation of the L. chinens and we screened the heal-promoting effects of the isolations in incision wound model.</p><p><b>RESULT</b>L. chinens significantly accelerates the wound healing of rat's skin, shortens the healing period, enhances the healing intensity and promotes the cell proliferation and blood vessels formation around the wounds. The isolations, which are petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, exert heal-promoting effects. It indicates that the possible morphon that promotes wound healing may exist in these three components, with small polar.</p><p><b>CONCLUSIONS</b>L. chinens possesses strong wound healing promoting effects, and the active constituent, with small polar, exists in petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, and we should focus on these three layers when carrying on further studies.</p>

[Effects of electroacupuncture pretreatment on ischemic arrhythmia and intracellular calcium oscillation in single cardiocyte isolated from rats with myocardial ischemia and reperfusion].

OBJECTIVE: To observe the inhibitory effects of acupuncture pretreatment on arrhythmia and intracellular calcium ([Ca2+]i) oscillation in single cardiocyte in rats subjected to myocardial ischemia-reperfusion (MIR). METHODS: Male SD rats were evenly randomized into normal control (NC), MIR and electroacupuncture (EA) groups. MIR was performed by ligation (30 min) and reperfusion (10 min) of the left anterior descending coronary artery in vivo in rats or in the isolated and perfused rat heart subjected to a 40 min global ischemia followed by a 10 min reperfusion. EA pretreatment was applied to bilateral "Neiguan" (PC 6) for 30 min once a day in 3 consecutive days. Arrhythmic score was calculated according to Curtis's and Walker's method, and the count of [Ca2+]i oscillation was measured by using InCytPm 2 intracellular ion detecting system. RESULTS: Both the arrhythmic score and the count of [Ca2+]i oscillation in MIR group were considerably higher than those in NC group (P<0.05). While compared with MIR group, the arrhythmia score and the count of [Ca2+]i oscillation in EA group were decreased significantly (P<0.05). CONCLUSION: Pretreatment of EA can effectively resist MIR-induced arrhythmia and intracellular calcium oscillation in the rat.

Hydroxysafflor yellow A up-regulates HIF-1alpha via inhibition of VHL and p53 in Eahy 926 cell line exposed to hypoxia / 药学学报

In present study, we investigated the mechanism of regulating HIF-1alpha expression by hydroxysafflor yellow A (HSYA) in Eahy 926 cell line under 1% O2 hypoxia. Eahy 926 cells were incubated with HSYA (100, 10 and 1 micromol x L(-1)) under hypoxia for the indicated time after treatment. Cell proliferation rate was detected using MTT assays. VHL and p53 location and protein expression were analyzed by immunocytochemical stain. HIF-1alpha, VHL and p53 mRNA expression were detected by RT-PCR. Protein expression of HIF-1alpha, VHL and p53 were assayed by Western blotting method. HSYA at 100 micromol x L(-1) increased Eahy 926 cells proliferation rate under hypoxia. HIF-1alpha mRNA and protein expression were up-regulated in the presence of HSYA. VHL, p53 mRNA and protein expression decreased significantly after 8 hours of treatment under hypoxia. HSYA protected Eahy 926 cells from hypoxia, and up-regulated HIF-1alpha expression partially via its inhibition of VHL and p53 expression.

[Effects of enflurane on myocardial reperfusion injury during cardiac surgery with cardiopulmonary bypass].

OBJECTIVE: To study the effects of inhalation enflurane (Enf) before aortic clamping on myocardial reperfusion injury in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: hirty patents undergoing selective cardiac valve replacement were randomly allocated to three groups. Group I and group II inhaled 1.0 MAC and 0.5 MAC Enf before clamping aorta, respectively. Group III was the control group interval administration with Fentanyl. RESULTS: Immediately upon aortic clamp release (T2), the value of CK-MB, MDA and SOD of all the groups was significantly increased, however,their concentration did not peak significantly until T3 and T4(10 and 30 min after clamp aorta release). The levels at 60 min (T5) and 24 hours (T6) aorta were lower than T4 but still higher than T(0). At T3 and T4, CK-MB levels in group I were significantly higher than those in II and III groups (P=0.0220, 0.0108 and 0.0202, 0.0295). At T6, the CK-MB level of group II was significantly higher than that of group III (P<0.0001). At T4 and T5, the MDA value of group I was higher than that of group II (P=0.0060 and 0.0364). Meanwhile, the SOD level in group I was also higher than that of group II and group III at the T4 point (P<0.0001 and 0.0084). There was a correlation between the CK-MB value and the aorta clamping time,correlation coefficient range being 0.55 - 0.81,(P<0.05). However, there was no correlation between the CK-MB and MDA, SOD. CONCLUSION: There is ischemia reperfusion injury during cardiac surgery CPB with the increase of OFR production and elevation of the antioxidant reserve. Inhalation of large dose of enflurane may result in increased myocardial ischemia reperfusion injury manifested by elevated levels of myocardial enzymes and OFR production.

Effects of enflurane on myocardial reperfusion injury during cardiac surgery with cardiopulmonary bypass / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the effects of inhalation enflurane (Enf) before aortic clamping on myocardial reperfusion injury in cardiac surgery with cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>hirty patents undergoing selective cardiac valve replacement were randomly allocated to three groups. Group I and group II inhaled 1.0 MAC and 0.5 MAC Enf before clamping aorta, respectively. Group III was the control group interval administration with Fentanyl.</p><p><b>RESULTS</b>Immediately upon aortic clamp release (T2), the value of CK-MB, MDA and SOD of all the groups was significantly increased, however,their concentration did not peak significantly until T3 and T4(10 and 30 min after clamp aorta release). The levels at 60 min (T5) and 24 hours (T6) aorta were lower than T4 but still higher than T(0). At T3 and T4, CK-MB levels in group I were significantly higher than those in II and III groups (P=0.0220, 0.0108 and 0.0202, 0.0295). At T6, the CK-MB level of group II was significantly higher than that of group III (P<0.0001). At T4 and T5, the MDA value of group I was higher than that of group II (P=0.0060 and 0.0364). Meanwhile, the SOD level in group I was also higher than that of group II and group III at the T4 point (P<0.0001 and 0.0084). There was a correlation between the CK-MB value and the aorta clamping time,correlation coefficient range being 0.55 - 0.81,(P<0.05). However, there was no correlation between the CK-MB and MDA, SOD.</p><p><b>CONCLUSION</b>There is ischemia reperfusion injury during cardiac surgery CPB with the increase of OFR production and elevation of the antioxidant reserve. Inhalation of large dose of enflurane may result in increased myocardial ischemia reperfusion injury manifested by elevated levels of myocardial enzymes and OFR production.</p>