Sexual dimorphism in the brain underlies behavioral differences between sexes.The bed nucleus of the stria terminalis(BNST)is a complex nucleus that differs between males and females,but the sexual dimorphism in cytoa...Sexual dimorphism in the brain underlies behavioral differences between sexes.The bed nucleus of the stria terminalis(BNST)is a complex nucleus that differs between males and females,but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision(ovBNST)remains largely unexplored.By combining snRNA-seq and transgenic labeling,we found a higher density of ovBNST proenkephalin(ovBNSTPENK)neurons in male than female mice.Anatomically,we virally mapped the efferents and afferents of ovBNSTPENK neurons,finding reciprocally dimorphic connections with the hypothalamus and striatum.Gene enrichment analysis suggests that ovBNSTPENK neurons are modulated by the upstream dopamine pathway.Functionally,by applying caspase-3-mediated depletion of ovBNSTPENK neurons,we found that loss of these neurons enhanced locomotor activity in male but not female mice,without altering the anxiety-like phenotypes in either sex.Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNSTPENK neurons from a sexually dimorphic perspective.展开更多
The occurrence of acute kidney injury(AKI)in critically ill patients is often associated with increased morbidity and mortality rates.Despite extensive research,a consensus is yet to be arrived,especially regarding th...The occurrence of acute kidney injury(AKI)in critically ill patients is often associated with increased morbidity and mortality rates.Despite extensive research,a consensus is yet to be arrived,especially regarding the optimal timing and indications for initiation of kidney replacement therapy(KRT)for critically ill patients.There is no clear guidance available on the timing of weaning from KRT.More recently,various biomarkers have produced promising prognostic pre-diction in such patients,regarding the need for KRT and its termination.Most of these biomarkers are indicative of kidney damage and stress,rather than re-covery.However,large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT.This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To ex...BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.展开更多
Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced mi...Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.展开更多
The present study utilized a nitroglycerin-induced rat model of migraine to detect the effects of rizatriptan benzoate on proenkephalin and substance P gene expression in the midbrain using real-time quantitative poly...The present study utilized a nitroglycerin-induced rat model of migraine to detect the effects of rizatriptan benzoate on proenkephalin and substance P gene expression in the midbrain using real-time quantitative polymerase chain reaction and investigate whether rizatriptan benzoate can regulate the endogenous pain modulatory system. The results showed that rizatriptan benzoate significantly reduced expression of the mRNAs for proenkephalin and substance P. Rizatriptan benzoate may inhibit the analgesic effect of the endogenous pain modulatory system.展开更多
基金supported by research grants from the STI2030-Major Projects(2021ZD0203000 and 2021ZD0203002)the Major Project of the National Natural Science Foundation of China(82090033)+3 种基金the National Natural Science Foundation of China(32200825,32471074,and 32100792)the Shandong Provincial Natural Science Foundation(ZR2022QC173)the Shandong Provincial Taishan Scholars Project(tsqn202306174)the Shandong Province Major Basic Research Project(ZR2019ZD35).
文摘Sexual dimorphism in the brain underlies behavioral differences between sexes.The bed nucleus of the stria terminalis(BNST)is a complex nucleus that differs between males and females,but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision(ovBNST)remains largely unexplored.By combining snRNA-seq and transgenic labeling,we found a higher density of ovBNST proenkephalin(ovBNSTPENK)neurons in male than female mice.Anatomically,we virally mapped the efferents and afferents of ovBNSTPENK neurons,finding reciprocally dimorphic connections with the hypothalamus and striatum.Gene enrichment analysis suggests that ovBNSTPENK neurons are modulated by the upstream dopamine pathway.Functionally,by applying caspase-3-mediated depletion of ovBNSTPENK neurons,we found that loss of these neurons enhanced locomotor activity in male but not female mice,without altering the anxiety-like phenotypes in either sex.Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNSTPENK neurons from a sexually dimorphic perspective.
文摘The occurrence of acute kidney injury(AKI)in critically ill patients is often associated with increased morbidity and mortality rates.Despite extensive research,a consensus is yet to be arrived,especially regarding the optimal timing and indications for initiation of kidney replacement therapy(KRT)for critically ill patients.There is no clear guidance available on the timing of weaning from KRT.More recently,various biomarkers have produced promising prognostic pre-diction in such patients,regarding the need for KRT and its termination.Most of these biomarkers are indicative of kidney damage and stress,rather than re-covery.However,large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT.This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.
基金Supported by National Natural Science Foundation of China,No.82300347Natural Science Foundation of Ningbo,No.2021J296Science Foundation of Lihuili Hospital,No.2022ZD004.
文摘BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.
文摘Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.
文摘The present study utilized a nitroglycerin-induced rat model of migraine to detect the effects of rizatriptan benzoate on proenkephalin and substance P gene expression in the midbrain using real-time quantitative polymerase chain reaction and investigate whether rizatriptan benzoate can regulate the endogenous pain modulatory system. The results showed that rizatriptan benzoate significantly reduced expression of the mRNAs for proenkephalin and substance P. Rizatriptan benzoate may inhibit the analgesic effect of the endogenous pain modulatory system.
