Objective Dexmedetomidine(DEX),the most specificα^(2)-adrenergic receptor agonist widely used for its sedative and analgesic properties,has been reported to upregulate HIF-1αexpression to protect hypoxic and ischemi...Objective Dexmedetomidine(DEX),the most specificα^(2)-adrenergic receptor agonist widely used for its sedative and analgesic properties,has been reported to upregulate HIF-1αexpression to protect hypoxic and ischemic tissues.However,it is largely unclear whether DEX can also upregulate Hypoxiainducible factor-1 alpha(HIF-1α)expression and its downstream vascular endothelial growth factor-A(VEGFA)in cancer tissues with oxygen-deficient tumor microenvironment.Methods We used SMMC-7721 cells,MHCC97-H cells,and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry(VM)and its mechanism.Under normoxic(20%O^(2))and hypoxic(1%O^(2))conditions,DEX was used to intervene cells,and yohimbine was used to rescue them.Results The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range,and the addition of yohimbine inhibited this effect.DEX could activate HIF-1α/VEGFA pathway,which was further verified by silencing HIF-1α.Consistently,in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression,and enhance the number of VM channels and microvessel density(MVD).Conclusion We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma,whereasα^(2)-adrenergic receptor mediation might be the critical mechanisms.展开更多
Background: Pausinystalia yohimbe (L.) is a member of the family Rubiaceae. It is a valuable medicinal tree, distributed in evergreen closed-canopy forests in West Africa. It is traditionally used for treatment of ere...Background: Pausinystalia yohimbe (L.) is a member of the family Rubiaceae. It is a valuable medicinal tree, distributed in evergreen closed-canopy forests in West Africa. It is traditionally used for treatment of erectile dysfunction and diabetes. Objective: This was an attempt to evaluate the effects of methanolic extract of P. yohimbe bark on blood glucose level in normal fasting rats. Methods: Different doses of methanolic extract of P. yohimbe bark (5, 10, 20, 40 and 80 mg/kg/mL) were orally administered to normal fasting rats to assess their effects on blood glucose levels. Results: The methanolic extract of P. yohimbe bark in different concentrations (5, 10, 20, 40 and 80 mg/kg/mL) when administered to normal fasting rats, only a considerable reduction (26.57 mg/dL) was produced by the dose of 20 mg/kg/mL. Conclusion and Recommendation: Although P. yohimbe has long been reported to regulate blood glucose levels;such effect is unclear and remains requiring further studies.展开更多
Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the additio...Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.展开更多
The Background: Tramadol, is a central acting analgesic that possesses weak affinity for the μ-opioid receptor and modifies transmission of nociceptive impulses through inhibition of monoamine reuptake. This study wa...The Background: Tramadol, is a central acting analgesic that possesses weak affinity for the μ-opioid receptor and modifies transmission of nociceptive impulses through inhibition of monoamine reuptake. This study was designed to determine the effect of tramadol on blood glucose levels and also to investigate whether or not alpha-2 adrenergic receptors were responsible for this effect. Methods: Twenty-five Wistar male rats were assigned to four groups to receive: Group I: saline;Group II: tramadol (1 mg·kg-1);Group III and Group IV: pretreatment with a2-receptor antagonist drugs yohimbine (1 mg·kg-1) or idazoxan (1 mg·kg-1), 30 min before administration of tramadol (1 mg·kg-1). Samples for plasma glucose measurement were withdrawn at 0, 30, 60, 90 and 120 minutes of the experiment. Results: A significant rise in blood glucose levels was observed following administration of i.v. tramadol. Pretreatment with both yohimbine and idazoxan (1 mg·kg-1) significantly attenuated tramadol-induced hyperglycemia. Conclusion: The results of the study indicate that, tramadol administered at an analgesic dose of 1 mg·kg-1 produces hyperglycemia in diethyl ether anesthetized rats. Reversal of this effect with a2-adrenoceptor blocking agents suggests that monoaminergic pathways which contribute to the analgesic action of tramadol, may have a role in the hyperglycemic action of the drug.展开更多
The asymmetric synthesis of 16,17,20-epi-deserpidine and a derivative of(-)-deserpidine has been achieved.Key feature s in the assembly of the pentacyclic framework include a visible-light photocatalytic intra-/inter-...The asymmetric synthesis of 16,17,20-epi-deserpidine and a derivative of(-)-deserpidine has been achieved.Key feature s in the assembly of the pentacyclic framework include a visible-light photocatalytic intra-/inter-/intramolecular radical cascade reaction to construct the tetracyclic ABCD ring system in one-pot and an intramolecularaldol reaction to forge the cyclohexane E ring.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province[LY19H160002]the Science and Technology Research Program of Jinhua City[2018-3-001b and 2017-3-020]
文摘Objective Dexmedetomidine(DEX),the most specificα^(2)-adrenergic receptor agonist widely used for its sedative and analgesic properties,has been reported to upregulate HIF-1αexpression to protect hypoxic and ischemic tissues.However,it is largely unclear whether DEX can also upregulate Hypoxiainducible factor-1 alpha(HIF-1α)expression and its downstream vascular endothelial growth factor-A(VEGFA)in cancer tissues with oxygen-deficient tumor microenvironment.Methods We used SMMC-7721 cells,MHCC97-H cells,and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry(VM)and its mechanism.Under normoxic(20%O^(2))and hypoxic(1%O^(2))conditions,DEX was used to intervene cells,and yohimbine was used to rescue them.Results The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range,and the addition of yohimbine inhibited this effect.DEX could activate HIF-1α/VEGFA pathway,which was further verified by silencing HIF-1α.Consistently,in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression,and enhance the number of VM channels and microvessel density(MVD).Conclusion We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma,whereasα^(2)-adrenergic receptor mediation might be the critical mechanisms.
文摘Background: Pausinystalia yohimbe (L.) is a member of the family Rubiaceae. It is a valuable medicinal tree, distributed in evergreen closed-canopy forests in West Africa. It is traditionally used for treatment of erectile dysfunction and diabetes. Objective: This was an attempt to evaluate the effects of methanolic extract of P. yohimbe bark on blood glucose level in normal fasting rats. Methods: Different doses of methanolic extract of P. yohimbe bark (5, 10, 20, 40 and 80 mg/kg/mL) were orally administered to normal fasting rats to assess their effects on blood glucose levels. Results: The methanolic extract of P. yohimbe bark in different concentrations (5, 10, 20, 40 and 80 mg/kg/mL) when administered to normal fasting rats, only a considerable reduction (26.57 mg/dL) was produced by the dose of 20 mg/kg/mL. Conclusion and Recommendation: Although P. yohimbe has long been reported to regulate blood glucose levels;such effect is unclear and remains requiring further studies.
文摘Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.
文摘The Background: Tramadol, is a central acting analgesic that possesses weak affinity for the μ-opioid receptor and modifies transmission of nociceptive impulses through inhibition of monoamine reuptake. This study was designed to determine the effect of tramadol on blood glucose levels and also to investigate whether or not alpha-2 adrenergic receptors were responsible for this effect. Methods: Twenty-five Wistar male rats were assigned to four groups to receive: Group I: saline;Group II: tramadol (1 mg·kg-1);Group III and Group IV: pretreatment with a2-receptor antagonist drugs yohimbine (1 mg·kg-1) or idazoxan (1 mg·kg-1), 30 min before administration of tramadol (1 mg·kg-1). Samples for plasma glucose measurement were withdrawn at 0, 30, 60, 90 and 120 minutes of the experiment. Results: A significant rise in blood glucose levels was observed following administration of i.v. tramadol. Pretreatment with both yohimbine and idazoxan (1 mg·kg-1) significantly attenuated tramadol-induced hyperglycemia. Conclusion: The results of the study indicate that, tramadol administered at an analgesic dose of 1 mg·kg-1 produces hyperglycemia in diethyl ether anesthetized rats. Reversal of this effect with a2-adrenoceptor blocking agents suggests that monoaminergic pathways which contribute to the analgesic action of tramadol, may have a role in the hyperglycemic action of the drug.
基金the financial surpport from the National Natural Science Foundation of China(Nos.21702140 and21732005)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(No.2018ZX09101003-005-004)。
文摘The asymmetric synthesis of 16,17,20-epi-deserpidine and a derivative of(-)-deserpidine has been achieved.Key feature s in the assembly of the pentacyclic framework include a visible-light photocatalytic intra-/inter-/intramolecular radical cascade reaction to construct the tetracyclic ABCD ring system in one-pot and an intramolecularaldol reaction to forge the cyclohexane E ring.
