Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has becom...Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.展开更多
Ong et al.investigated the impact of area deprivation index(ADI),a measure of neighborhood-level socioeconomic deprivation,on baseline severity of rhegmatogenous retinal detachments(RRDs),as measured by visual acuity ...Ong et al.investigated the impact of area deprivation index(ADI),a measure of neighborhood-level socioeconomic deprivation,on baseline severity of rhegmatogenous retinal detachments(RRDs),as measured by visual acuity and foveal involvement at the time of presentation to ophthalmologic care(1).Their key finding was that a presenting visual acuity worse than 20/40 and/or foveal involving RRD were associated with a high ADI,suggesting that higher ADI(meaning greater socioeconomic disadvantage)contributes to the delay in presentation to care.It is well understood that the delayed care for RRDs leads to worse ultimate visual outcomes and surgical success rates(2-4).Further,their findings contribute to the existing body of literature that suggests socioeconomic deprivation contributes overall to poor health.展开更多
BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen depr...BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.展开更多
Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate...Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.展开更多
Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition th...Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.展开更多
Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespec...Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespecific membrane antigen positron emission tomography(PSMA-PET/CT)imaging have prompted growing interest in personalized,risk-adapted management strategies.This study by the Turkish Society for Radiation Oncology aims to examine radiation oncologists’practices in managing IR-PC,focusing on RT and imaging modalities to identify trends for personalized treatments.Methods:A cross-sectional survey was conducted among Turkish radiation oncologists treating at least 50 prostate cancer(PC)cases annually.The 22-item questionnaire covered IR-PC management aspects such as risk stratification,imaging preferences,androgen deprivation therapy(ADT)use and duration,RT techniques,and treatment combinations.Anonymous responses were analyzed using descriptive statistics.Results:Thirty radiation oncologists participated,57%with over 20 years of experience.The median annual number of PC cases treated was 130.For risk stratification,43% followed the National Comprehensive Cancer Network(NCCN)guidelines,while 30%used the D’Amico classification.Imaging preferences revealed 47% favored PSMA-PET/CT.External beam RT was universally preferred,with 60% adopting ultra-hypofractionation.ADT was used by 97%,with 73% recommending it for unfavorable IR-PC cases.Short-term ADT(4–6 months)was the standard,administered concurrently with RT by 57%.Cardiovascular status influenced decisions for 97% of respondents,while 37% also considered patient age,preferences,and sexual health.Conclusions:This national survey demonstrates a shift toward personalized care in intermediate-risk prostate cancer in Turkey,marked by selective PSMA-PET/CT use,tailored ADT,and evolving radiotherapy practices.The findings underscore the importance of multidisciplinary collaboration—particularly between urologists and radiation oncologists—to optimize imaging integration and treatment outcomes.展开更多
Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we id...Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.展开更多
Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain,yet the precise neural mechanisms underlying this association remain elusive.In our study,we explored the...Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain,yet the precise neural mechanisms underlying this association remain elusive.In our study,we explored the contribution of cholinergic neurons within the medial habenula(MHb)to hyperalgesia induced by sleep deprivation in rats.Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results.Interestingly,we did not find a direct response of MHb cholinergic neurons to pain stimulation.Further investigation identified the interpeduncular nucleus(IPN)and the paraventricular nucleus of the thalamus(PVT)as key players in the pro-nociceptive effect of sleep deprivation.Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia.These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation,highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.展开更多
The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the s...The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the success of social reintegration.This study estimated the influence of the household’s socioeconomic status(SES)on these psychosocial difficulties.This study is based on a prospective multicentric database and focused on children who received a psychosocial evaluation during their follow-up from 2013 to 2020.We retrieved data on school and psychological difficulties.Household SES was estimated by a social deprivation score.Data from1003 patients were analyzed.School difficulties were noted in 22%of CCS.A greater social deprivation was significantly associated with school difficulty.Tumor relapse,treatment with hematopoietic stem cell transplantation,and central nervous system(CNS)tumors remained significant risk factors.In the subgroup of CNS tumors,school difficulties were increased and associated with greater social deprivation.Psychological difficulties were not associated with the deprivation score.There is a link between SES and school difficulties in CCS.Further investigations should be carried out for children with CNS tumors,which is the population of the greatest concern.展开更多
Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plast...Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.展开更多
Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor growth.To efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous de...Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor growth.To efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous deprivation without precise control will introduce toxicity to normal cells.Herein,a programmable double-unlock nanocomplex(ROCK)was prepared,which could self-supply phenylalanine ammonia-lyase(PAL)to tumor cells for phenylalanine(Phe)deprivation.ROCK was double-locked in physiological conditions when administered systemically.While ROCK actively targeted to tumor cells by integrinαvβ3/5 and CD44,ROCK was firstly unlocked by cleavage of protease on tumor cell membrane,exposing CendR and R8 to enhance endocytosis.Then,hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells,in which ROCK was secondly unlocked,resulting in pro-moting endo/lysosome escape and PAL plasmid(pPAL)release.Released pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe,thereby block-ing the protein synthesis and killing tumor cells specifically.Overall,our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells,providing new insights to efficiently remove intratumoral nutrition for cancer therapy.展开更多
Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspri...Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.展开更多
Objective:The relationship between cause-specific mortality and regional socio-economic and environmental indicators remains poorly studied in Russia.The study first aims to study regional differences in cause-specifi...Objective:The relationship between cause-specific mortality and regional socio-economic and environmental indicators remains poorly studied in Russia.The study first aims to study regional differences in cause-specific mortality among the population aged 20 years and older in Russia,and second to investigate the association between regional deprivation and cause-specific mortality.Material and methods:Russian deprivation index was used to measure level of deprivation.The index consists of three components:social,economic and environmental.The index measures general deprivation,and its compo-nents measure social,economic and environmental deprivation.The mortality data by age(five-year groups)and sex in the subjects of Russia from 2006 to 2022 were extracted from the Russian Fertility and Mortality Database of the Center of Demographic Research of the New Economic School.Results:In the most general deprived areas,mortality rate from infectious and parasitic diseases increased by more than twice in the total population,women and men as compared to the least deprived quantile(Q1).Fully adjusted negative binomial regression showed an increase in mortality rate from injuries,poisoning and external causes and infectious and parasitic diseases in more social deprived areas as compared to Q1 in the total population,women and men.In men,there was a significantly higher mortality rate from neoplasms and from infectious and parasitic diseases in more economic deprived areas as compared to Q1.Both in total population and in women,there was a trend towards an increase in mortality from neoplasms depending on the level of environmental deprivation.Conclusions:This is the first study examining the relationship of contextual factors with cause-specific mortality that takes into account sex,age and year of death at the population level in Russia.General,social,economic and environmental deprivation are associated with cause-specific mortality.展开更多
BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported result...BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.展开更多
Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced a...Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.展开更多
Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment p...Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment costs.IADT may also delay the progression to castration-resistant prostate cancer.However,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials.Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and analysis.The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs.continuous androgen deprivation therapy for the treatment of prostate cancer.The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)burden.Based on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.展开更多
Objective To observe the effect of application of garlic paste at Shenque （神阙 CV8） on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Me...Objective To observe the effect of application of garlic paste at Shenque （神阙 CV8） on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Medical University were randomly divided into three groups： normal group （A）, sleep deprivation group （B） and treatment group （C）. Volunteers in group B and C received 48 h sleep deprivation （SD）, and in the mean time volunteers in group C were treated by garlic paste at Shenque （神阙 CV8）, while those in group A had no any treatment. The body temperature of all the volunteers was detected at 6：00 am, 12：00 am, 6：00 pm and 0：00 am, respectively, after the treatment. Results The mean body temperature values in group A and C both were highest at 6： 00 pm and lowest at 6： 00 am which had a significant difference in each group （P〈0.01）; in group B, the mean body temperature was highest at 0：00 am and lowestat 6：00 am, no significant difference was found between them （P〉0.05）. Results of cosine analysis showed that in subjects of group B the circadian rhythm of body temperature still kept going well after SD, but the peak amplitude and amplitude of vibration were higher than those of group A, and the acrophase of group B was obviously lower than that of group C and A. The 3 indexes of group C were similar to those of group A, denoting that garlic paste application of Shenque （神阙 CV8） could prevent disorders of circadian rhythm of the body temperature. Conclusion The garlic paste application at Shenque （神阙 CV8） can adjust circadian rhythm and accelerate the recovery processes of circadian rhythm in SD young students.展开更多
Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, ...Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.展开更多
Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotect...Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.展开更多
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an...Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.展开更多
基金supported by the National Natural Science Foundation of China(U21A20418).
文摘Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.
文摘Ong et al.investigated the impact of area deprivation index(ADI),a measure of neighborhood-level socioeconomic deprivation,on baseline severity of rhegmatogenous retinal detachments(RRDs),as measured by visual acuity and foveal involvement at the time of presentation to ophthalmologic care(1).Their key finding was that a presenting visual acuity worse than 20/40 and/or foveal involving RRD were associated with a high ADI,suggesting that higher ADI(meaning greater socioeconomic disadvantage)contributes to the delay in presentation to care.It is well understood that the delayed care for RRDs leads to worse ultimate visual outcomes and surgical success rates(2-4).Further,their findings contribute to the existing body of literature that suggests socioeconomic deprivation contributes overall to poor health.
文摘BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.
文摘Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.
基金financial support of Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020095)National Natural Science Foundation of China(No.52073140)。
文摘Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.
文摘Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespecific membrane antigen positron emission tomography(PSMA-PET/CT)imaging have prompted growing interest in personalized,risk-adapted management strategies.This study by the Turkish Society for Radiation Oncology aims to examine radiation oncologists’practices in managing IR-PC,focusing on RT and imaging modalities to identify trends for personalized treatments.Methods:A cross-sectional survey was conducted among Turkish radiation oncologists treating at least 50 prostate cancer(PC)cases annually.The 22-item questionnaire covered IR-PC management aspects such as risk stratification,imaging preferences,androgen deprivation therapy(ADT)use and duration,RT techniques,and treatment combinations.Anonymous responses were analyzed using descriptive statistics.Results:Thirty radiation oncologists participated,57%with over 20 years of experience.The median annual number of PC cases treated was 130.For risk stratification,43% followed the National Comprehensive Cancer Network(NCCN)guidelines,while 30%used the D’Amico classification.Imaging preferences revealed 47% favored PSMA-PET/CT.External beam RT was universally preferred,with 60% adopting ultra-hypofractionation.ADT was used by 97%,with 73% recommending it for unfavorable IR-PC cases.Short-term ADT(4–6 months)was the standard,administered concurrently with RT by 57%.Cardiovascular status influenced decisions for 97% of respondents,while 37% also considered patient age,preferences,and sexual health.Conclusions:This national survey demonstrates a shift toward personalized care in intermediate-risk prostate cancer in Turkey,marked by selective PSMA-PET/CT use,tailored ADT,and evolving radiotherapy practices.The findings underscore the importance of multidisciplinary collaboration—particularly between urologists and radiation oncologists—to optimize imaging integration and treatment outcomes.
基金National Natural Science Foundation of China(81870850)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0322)。
文摘Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203204)the National Natural Science Foundation of China(32030052 and 31530028).
文摘Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain,yet the precise neural mechanisms underlying this association remain elusive.In our study,we explored the contribution of cholinergic neurons within the medial habenula(MHb)to hyperalgesia induced by sleep deprivation in rats.Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results.Interestingly,we did not find a direct response of MHb cholinergic neurons to pain stimulation.Further investigation identified the interpeduncular nucleus(IPN)and the paraventricular nucleus of the thalamus(PVT)as key players in the pro-nociceptive effect of sleep deprivation.Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia.These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation,highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.
基金supported by a grant from SFCE INCa (Institut National du Cancer)GOCE (Grand Ouest Cancer de l’Enfant).
文摘The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the success of social reintegration.This study estimated the influence of the household’s socioeconomic status(SES)on these psychosocial difficulties.This study is based on a prospective multicentric database and focused on children who received a psychosocial evaluation during their follow-up from 2013 to 2020.We retrieved data on school and psychological difficulties.Household SES was estimated by a social deprivation score.Data from1003 patients were analyzed.School difficulties were noted in 22%of CCS.A greater social deprivation was significantly associated with school difficulty.Tumor relapse,treatment with hematopoietic stem cell transplantation,and central nervous system(CNS)tumors remained significant risk factors.In the subgroup of CNS tumors,school difficulties were increased and associated with greater social deprivation.Psychological difficulties were not associated with the deprivation score.There is a link between SES and school difficulties in CCS.Further investigations should be carried out for children with CNS tumors,which is the population of the greatest concern.
基金supported by the National Key R&D Program of China(Nos.2022YFC3400700,2022YFA0806600)the National Natural Science Foundation of China(Nos.22277093,22074110,21721005)+2 种基金the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCGW-2022-008)the Wuhan Knowledge Innovation Project(No.2022020801010111)the Natural Science Foundation of Hubei Province(No.2022CFB569).
文摘Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.
基金supported by funds of Sichuan Province for Distinguished Young Scholar(No.2021JDJQ0037)the National Natural Science Foundation of China(No.82172094).
文摘Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor growth.To efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous deprivation without precise control will introduce toxicity to normal cells.Herein,a programmable double-unlock nanocomplex(ROCK)was prepared,which could self-supply phenylalanine ammonia-lyase(PAL)to tumor cells for phenylalanine(Phe)deprivation.ROCK was double-locked in physiological conditions when administered systemically.While ROCK actively targeted to tumor cells by integrinαvβ3/5 and CD44,ROCK was firstly unlocked by cleavage of protease on tumor cell membrane,exposing CendR and R8 to enhance endocytosis.Then,hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells,in which ROCK was secondly unlocked,resulting in pro-moting endo/lysosome escape and PAL plasmid(pPAL)release.Released pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe,thereby block-ing the protein synthesis and killing tumor cells specifically.Overall,our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells,providing new insights to efficiently remove intratumoral nutrition for cancer therapy.
基金supported by the National Natural Science Foundation of China(32371030,82071395)Natural Science Foundation of Chongqing(CSTB2024NSCQ-LZX0008)+1 种基金Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN202300424)CQMU Program for Youth Innovation in Future Medicine(W0044)。
文摘Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.
文摘Objective:The relationship between cause-specific mortality and regional socio-economic and environmental indicators remains poorly studied in Russia.The study first aims to study regional differences in cause-specific mortality among the population aged 20 years and older in Russia,and second to investigate the association between regional deprivation and cause-specific mortality.Material and methods:Russian deprivation index was used to measure level of deprivation.The index consists of three components:social,economic and environmental.The index measures general deprivation,and its compo-nents measure social,economic and environmental deprivation.The mortality data by age(five-year groups)and sex in the subjects of Russia from 2006 to 2022 were extracted from the Russian Fertility and Mortality Database of the Center of Demographic Research of the New Economic School.Results:In the most general deprived areas,mortality rate from infectious and parasitic diseases increased by more than twice in the total population,women and men as compared to the least deprived quantile(Q1).Fully adjusted negative binomial regression showed an increase in mortality rate from injuries,poisoning and external causes and infectious and parasitic diseases in more social deprived areas as compared to Q1 in the total population,women and men.In men,there was a significantly higher mortality rate from neoplasms and from infectious and parasitic diseases in more economic deprived areas as compared to Q1.Both in total population and in women,there was a trend towards an increase in mortality from neoplasms depending on the level of environmental deprivation.Conclusions:This is the first study examining the relationship of contextual factors with cause-specific mortality that takes into account sex,age and year of death at the population level in Russia.General,social,economic and environmental deprivation are associated with cause-specific mortality.
文摘BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.
文摘Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.
基金Ferring Pharmaceuticals provided funding for editorial assistance.The author acknowledges Dr.Payal Bhardwaj of Tata Consultancy Services,who provided editorial assistance.
文摘Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment costs.IADT may also delay the progression to castration-resistant prostate cancer.However,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials.Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and analysis.The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs.continuous androgen deprivation therapy for the treatment of prostate cancer.The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)burden.Based on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.
文摘Objective To observe the effect of application of garlic paste at Shenque （神阙 CV8） on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Medical University were randomly divided into three groups： normal group （A）, sleep deprivation group （B） and treatment group （C）. Volunteers in group B and C received 48 h sleep deprivation （SD）, and in the mean time volunteers in group C were treated by garlic paste at Shenque （神阙 CV8）, while those in group A had no any treatment. The body temperature of all the volunteers was detected at 6：00 am, 12：00 am, 6：00 pm and 0：00 am, respectively, after the treatment. Results The mean body temperature values in group A and C both were highest at 6： 00 pm and lowest at 6： 00 am which had a significant difference in each group （P〈0.01）; in group B, the mean body temperature was highest at 0：00 am and lowestat 6：00 am, no significant difference was found between them （P〉0.05）. Results of cosine analysis showed that in subjects of group B the circadian rhythm of body temperature still kept going well after SD, but the peak amplitude and amplitude of vibration were higher than those of group A, and the acrophase of group B was obviously lower than that of group C and A. The 3 indexes of group C were similar to those of group A, denoting that garlic paste application of Shenque （神阙 CV8） could prevent disorders of circadian rhythm of the body temperature. Conclusion The garlic paste application at Shenque （神阙 CV8） can adjust circadian rhythm and accelerate the recovery processes of circadian rhythm in SD young students.
文摘Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.
基金supported in part by the National Natural Science Foundation of China,No.81573644(to LMH),81573733(to SWX)the Tianjin 131 Innovative Team Project,China(to HW)+5 种基金the National Major Science and Technology Project of China,No.2012ZX09101201-004(to SWX)the Science and Technology Plan Project of Tianjin of China,No.16PTSYJC00120(to LMH)the Applied Foundation and Frontier Technology Research Program of Tianjin of China(General Project),No.14JCYBJC28900(to SXW)the National International Science and Technology Cooperation Project of China,No.2015DFA30430(to HW)the Key Program of the Natural Science Foundation of Tianjin of China,No.16ICZDJC36300(to HW)the Scientific Research and Technology Development Plan Project of Guangxi Zhuang Autonomous Region of China,No.14125008-2-5(to SXW)
文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.
基金supported by the National Natural Science Foundation of China,No.81430102(to QGW)
文摘Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.
