Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
With the increasing accumulation of plastic pollutants in various environments,research on microorganisms(including bacteria,fungi,and algae)with plastic degradation capabilities has gained significant attention.Howev...With the increasing accumulation of plastic pollutants in various environments,research on microorganisms(including bacteria,fungi,and algae)with plastic degradation capabilities has gained significant attention.However,only a limited number of microbial plastic-degrading enzymes have been identified to date.This highlights that the degradation mechanisms employed by many plastic-degrading microorganisms,particularly filamentous fungi,remain insufficiently explored.In this study,we utilized a versatile fungal plasmid(pCT74)to express green fluorescent protein(GFP)in a marine-derived fungus Alternaria alternata strain FB1 with plastic degradation capabilities.Upon evaluating the degradation effect of polyester-type polyurethane(PU)film,we observed that different transformants exhibited three kinds of activities(the same,reduced,or enhanced degradation capability)compared to the FB1 wild-type strain.Further analysis of the plasmid fragment insertion sites in different transformants revealed that pCT74 integrates randomly into the genome of the host fungus.Notably,a direct correlation was found between the plasmid insertion site and the degradation capability of the corresponding transformant.Our findings not only redefine the potential applications of plasmid pCT74 in filamentous fungi but also show a novel research approach to identifying key enzymes involved in plastic degradation by fungi.展开更多
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
基金Supported by the Science and Technology Innovation Project of Laoshan Laboratory(Nos.2022QNLM030004-3,LSKJ202203103)the NSFC Innovative Group Grant(No.42221005)+5 种基金the Key Collaborative Research Program of the Alliance of International Science Organizations(No.ANSO-CR-KP-2022-08)the Shandong Provincial Natural Science Foundation(No.ZR2021ZD28)the Major Research Plan of the National Natural Science Foundation(No.92351301)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA22050301)the Taishan Scholars Program(No.tstp20230637)the Qingdao Natural Science Foundation(No.23-2-1-182-zyyd-jch)。
文摘With the increasing accumulation of plastic pollutants in various environments,research on microorganisms(including bacteria,fungi,and algae)with plastic degradation capabilities has gained significant attention.However,only a limited number of microbial plastic-degrading enzymes have been identified to date.This highlights that the degradation mechanisms employed by many plastic-degrading microorganisms,particularly filamentous fungi,remain insufficiently explored.In this study,we utilized a versatile fungal plasmid(pCT74)to express green fluorescent protein(GFP)in a marine-derived fungus Alternaria alternata strain FB1 with plastic degradation capabilities.Upon evaluating the degradation effect of polyester-type polyurethane(PU)film,we observed that different transformants exhibited three kinds of activities(the same,reduced,or enhanced degradation capability)compared to the FB1 wild-type strain.Further analysis of the plasmid fragment insertion sites in different transformants revealed that pCT74 integrates randomly into the genome of the host fungus.Notably,a direct correlation was found between the plasmid insertion site and the degradation capability of the corresponding transformant.Our findings not only redefine the potential applications of plasmid pCT74 in filamentous fungi but also show a novel research approach to identifying key enzymes involved in plastic degradation by fungi.