The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new ...The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new physical therapy for the treatment of sleep disorders,with the advantages of being noninvasive and having few side effects.However,the mechanism by which phototherapy improves cognitive impairment caused by sleep disorders remains unclear.In this study,we used phototherapy combined with optogenetic technology to investigate the effect of noninvasive phototherapy on cognitive functions in sleep-deprived mice.Our results suggest that phototherapy might improve cognitive functions in sleep-deprived mice by modulating the hippocampus.Our study expands the research progress on noninvasive phototherapy for the treatment of sleep disorders.展开更多
Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of ...Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.展开更多
Around the year 140 BC the Evo, the famous imperial Han Dynasty took power in China and then sent some representatives to the western land in order to communicate with the West in addition to know the political, milit...Around the year 140 BC the Evo, the famous imperial Han Dynasty took power in China and then sent some representatives to the western land in order to communicate with the West in addition to know the political, military, geographical, economic and cultural situations of that region, it provides the basis for opening the way to the West. In this regard, they traveled to Iran and accordingly the formal relations were established between the Iranian and the Western governments and finally the Silk Road with a distance of about 8000 km has been emerged and started from the East and ended to Mediterranean Sea in the West. The aim of this study is to show that the Silk Road links throughout the world and its people together in thousands of years and the countries, cities and villages located in this road have been affected by developments or had affected and vivifying of it will lead to develop of the deprived urban and rural areas according to the abundant tourist attractions. This study which has used the historical and analytical method with practical purpose shows that cultural, scientific, religious and commercial exchanges between East and West were wide and many cities and villages were profiting of this gift. In this regard, vivifying of this road will lead to grow the underserved urban and rural areas according to many tourist attractions of the cities and villages.展开更多
This study aims to explore the effect and mechanism of Jiao-tai-wan （JTW） on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant （OR） rats with chronic partial sleep deprivation ...This study aims to explore the effect and mechanism of Jiao-tai-wan （JTW） on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant （OR） rats with chronic partial sleep deprivation （PSD）. OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose （FPG）, fasting insulin （FINS）, homeostasis model assessment-insulin resistance （HOMA-IR） and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 （Cryl） and cryptochrome 2 （Cry2） in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B （NF-κB） p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3＇, 5＇-monophosphate （cAMP） and activity of vasodilator-stimulated phosphoprotein （VASP） in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.展开更多
Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular...Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 （NOX2） was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco＇s modified Eagle＇s medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen, species in astrocytes subjected to ischemia-＇reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine （8-OHdG）, 4-hydroxy-2-nonenal （4-HNE） and 3-nitrotyrosin （3-NT） in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin im- proved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.展开更多
OBJECTIVE:To investigate the effects of acupuncture on learning and memory impairment,oxidative stress and autophagy induced by sleep depriv ation in rats,and to analyze the related mechanism.METHODS:Thirty Wistar rat...OBJECTIVE:To investigate the effects of acupuncture on learning and memory impairment,oxidative stress and autophagy induced by sleep depriv ation in rats,and to analyze the related mechanism.METHODS:Thirty Wistar rats were randomly divided into a normal group,sleep deprivation group and acupuncture group.The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation method.The Baihui(GV20),Shenmen(HT7)and Sanyinjiao(SP6)acupoints of rats were located to give electroacupuncture(density wave,frequency 20 Hz,intensity 1 mA)to maintain the needle feeling,and to keep the needle for 15min and continuous acupuncture for 7 d.The spatial learning and memory abilities of the rats were detected by the water maze test.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GPX)in the brain were detected by an assay kit,and the autophagy related proteins light chain 3 alpha(LC3A),light chain 3 beta(LC3B)and Beclin 1 and the activation of the protein kinase B(PKB/AKT)and mechanistic target of rapamycin(mTOR)signaling pathway in the rat's brain were detected by Western blotting.RESULTS:Compared with the normal group,the time spent in the target quadrant(P<0.05)and the number of times entering the target quadrant(P<0.05)in the rats of sleep deprivation group were significantly reduced,and the content of MDA was significantly increased(P<0.01),while the activities of SOD and GPX(P<0.01)in the brain were significantly decreased,and LC3AⅡ/Ⅰ,LC3BⅡ/Ⅰand Beclin 1 increased significantly(P<0.01),while pAKT(ser473)/AKT,p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70S6 decreased significantly(P<0.01).Compared with the sleep deprivation group,the time spent in the target quadrant and the times of entering the target quadrant(P<0.05)in the rats of acupuncture group after 7 d of treatment were significantly increased,Additionally,the content of MDA was significantly decreased(P<0.05),while the activities of SOD and GPX(P<0.05)in the brain were significantly increased.Moreover,the levels of LC3AⅡ/Ⅰ,LC3BⅡ/Ⅰand Beclin 1 decreased significantly(P<0.05),and that of pAKT(ser473)/AKT,p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70s6k increased significantly(P<0.05).CONCLUSION:Acupuncture can significantly improve the learning and memory damage caused by sleep deprivation and inhibit oxidative stress and autophagy,and its effect is related to the activation of AKT/mTOR signaling.展开更多
The habenular nucleus （Hb） is an important structure that regulates the function of the pineal gland which may affect melatonin content in the pineal gland after sleep deprivation （SD）. In the present study, high ...The habenular nucleus （Hb） is an important structure that regulates the function of the pineal gland which may affect melatonin content in the pineal gland after sleep deprivation （SD）. In the present study, high performance liquid chromatography showed that the melatonin content in the pineal gland was significantly reduced, and y-aminobutyric acid content in the Hb was significantly increased after SD. Furthermore, the melatonin content in the pineal gland was markedly reduced after Hb lesion under normal sleep and SD conditions. Immunohistochemistry showed that the number of Fos-positive neurons was significantly decreased in the lateral and medial Hb after SD. The findings demonstrate that the reduction of melatonin in the pineal gland after SD is related to decreased activity of Hb neurons, and that the Hb can regulate sleep-wake rhythm by influencing melatonin secretion in the pineal gland.展开更多
Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals ...Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.展开更多
Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
Objective: To explore the effect and mechanism of Jiaotai Pill(交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation(PSD). Methods: Obesity resistant(OR) rats were selected, and unde...Objective: To explore the effect and mechanism of Jiaotai Pill(交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation(PSD). Methods: Obesity resistant(OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide(LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin(Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes(Cry1 and Cry2) in the intestine were also determined. Results: The treatment of JTW significantly decreased LPS level in OR rats with PSD(P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting(P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. Conclusions: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.展开更多
Background:Sleep deprivation causes hippocampal injury,manifesting as neuronal damage and learning-memory impairment.These negative effects may be associated with disturbance of hippocampal glutamate and water homeost...Background:Sleep deprivation causes hippocampal injury,manifesting as neuronal damage and learning-memory impairment.These negative effects may be associated with disturbance of hippocampal glutamate and water homeostasis,which induces excessive neuronal excitability.Five percent CO_(2) inhalation has been shown to suppress neuronal excitability.Here,we aimed to investigate whether 5%CO_(2) inhalation facilitates the recovery of hippocampal glutamate and water homeostasis,neuron morphology,and learning-memory ability in sleep-deprived rats.Methods:Thirty-six Sprague-Dawley female rats were randomly divided into three groups including normal sleep(Group 1,NS,n=12),sleep deprivation followed by sleep recovery(Group 2,SD+SR,n=12),sleep deprivation followed by sleep recovery and 5%CO_(2) inhalation(Group 3,SD+SR+CO_(2),n=12)by random number table.Each group was divided into two subgroups(n=6 each subgroup)for different experiments randomly by random number table.Results:We found that 5%CO_(2) inhalation facilitated the recovery of hippocampal glutamate concentration(7.549±0.310,8.716±0.463,and 7.493±0.281 mmol/L at Days 1,3,and 5 in Group 3,F 2,15=22.06,p<0.0001)and hippocampal apparent diffusion coefficient mean value(8.210±0.274,7.685±0.171,8.265±0.269 at Days 1,3,and 5 in Group 3,F 2,15=10.45,p=0.0014),enhanced expression level of astrocyte-specific membrane protein glutamate transporter-1,promoted the polarized distribution of aquaporin 4,reduced hippocampal neuronal damage and improved learning-memory ability in sleep-deprived rats.Conclusion:This study showed that 5%CO_(2) inhalation can serve as a novel strategy for alleviating sleep deprivation-induced hippocampal injury.展开更多
Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve rep...Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.展开更多
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
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 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
Objective This study aimed to investigate the protective effect and mechanism of Senkyunolide A(SenA)on oxygen-glucose deprivation/reoxygenation(OGD/R)-induced injury in mouse hippocampal neuronal HT22 cells,providing...Objective This study aimed to investigate the protective effect and mechanism of Senkyunolide A(SenA)on oxygen-glucose deprivation/reoxygenation(OGD/R)-induced injury in mouse hippocampal neuronal HT22 cells,providing experimental evidence for elucidating the application of SenA in the prevention and treatment of cerebral ischemia–reperfusion injury.Methods An HT22 cell injury model was established using the OGD/R method and divided into the Control group,Model(OGD/R)group,Edaravone(EDA)group(OGD/R+EDA),and SenA group(OGD/R+SenA).Cell viability was detected by Cell counting kit-8(CCK-8)assay;live and dead cells were observed by Calcein AM/PI cell viability assay kit(Calcein-AM/PI)double staining;intracellular reactive oxygen species(ROS)levels were measured using the H2DCFDA(DCFH-DA)fluorescent probe;levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)were determined by biochemical kits;apoptosis rate was detected by flow cytometry;protein expression levels of Bcl-2-associated X protein(Bax),B-cell lymphoma 2(Bcl-2),and Cysteine-dependent aspartate-specific protease-3(Caspase-3)were measured by Western blot.Results Compared with the Control group,the OGD/R group showed significantly reduced cell viability(p<0.001),increased proportions of dead cells,ROS and MDA levels,and apoptosis rate(p<0.001),decreased SOD activity and GSH levels(p<0.05;p<0.001),significantly upregulated protein expression of Bax and Caspase-3(p<0.01;p<0.001),and downregulated Bcl-2 expression(p<0.001).Compared with the OGD/R group,both SenA and EDA significantly increased cell viability(p<0.001),reduced the proportion of dead cells,ROS and MDA levels,and apoptosis rate(p<0.001),upregulated SOD activity and GSH levels(p<0.01;p<0.001),downregulated protein expression of Bax and Caspase-3(p<0.01;p<0.001),and upregulated Bcl-2 expression(p<0.001).Conclusion SenA can alleviate OGD/R-induced neuronal injury by mitigating oxidative stress and inhibiting cell apoptosis.This study provides modern experimental evidence for the traditional theory of Chuanxiong in“promoting blood circulation,removing blood stasis,and unblocking brain collaterals,”and offers new insights for the prevention and treatment of ischemia–reperfusion brain injury with traditional Chinese medicine.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
Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually a...Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT.The PubMed database was searched for studies published over the past 20 years.We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT.The primary outcome measure was the sexual function.Studies assessed sexual function using quality of life patient-reported outcome measures,which included sexual potency/activity evaluation.Information from 2947 patients was analyzed in this review.The median age of patients was 70 years.At baseline,a median of 49.9%(95%confidence interval[Cl]:49.1%-50.7%)of the patients reported being sexually active.At 6 months,12 months,and 2 years or later of ADT treatment,a median of 10.3%(95%Cl:10.2%-10.5%),8.9%(95%Cl:8.6%-9.2%),and 8.3%(95%Cl:8.2%-8.5%)of the patients reported being sexually active,respectively.Considering that half of the patients were sexually active at baseline,it seems probable that more than 10%of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT.In conclusion,despite the common belief that ADT eliminates sexual activity,this analysis found that approximately 1 in 10 men are sexually active when on ADT,and this proportion is likely increased in men who are sexually active before starting ADT.Attention to sexual activity should not be dismissed in men on ADT.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
This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of ...This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of night shifts and nega-tive cardiometabolic outcomes,such as elevated resting pulse rates and lowered levels of high-density lipoprotein cholesterol.These outcomes underscore the health risks linked to partial sleep deprivation,a common challenge in military environments.The editorial highlights the clinical significance of these findings,advocating for the implementation of targeted health interventions to mitigate these risks.Strategies such as structured sleep recovery programs and lifestyle modifications are recommended to improve the health management of military personnel engaged in nocturnal duties.By addressing these issues,military health management can better safeguard the well-being and operational readiness of its personnel.展开更多
基金Supported by the Tianjin Municipal Education Commission Scientic Research Project No.2023YXZD10。
文摘The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new physical therapy for the treatment of sleep disorders,with the advantages of being noninvasive and having few side effects.However,the mechanism by which phototherapy improves cognitive impairment caused by sleep disorders remains unclear.In this study,we used phototherapy combined with optogenetic technology to investigate the effect of noninvasive phototherapy on cognitive functions in sleep-deprived mice.Our results suggest that phototherapy might improve cognitive functions in sleep-deprived mice by modulating the hippocampus.Our study expands the research progress on noninvasive phototherapy for the treatment of sleep disorders.
基金financially supported by the Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines(21DZ2270500)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02).
文摘Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.
文摘Around the year 140 BC the Evo, the famous imperial Han Dynasty took power in China and then sent some representatives to the western land in order to communicate with the West in addition to know the political, military, geographical, economic and cultural situations of that region, it provides the basis for opening the way to the West. In this regard, they traveled to Iran and accordingly the formal relations were established between the Iranian and the Western governments and finally the Silk Road with a distance of about 8000 km has been emerged and started from the East and ended to Mediterranean Sea in the West. The aim of this study is to show that the Silk Road links throughout the world and its people together in thousands of years and the countries, cities and villages located in this road have been affected by developments or had affected and vivifying of it will lead to develop of the deprived urban and rural areas according to the abundant tourist attractions. This study which has used the historical and analytical method with practical purpose shows that cultural, scientific, religious and commercial exchanges between East and West were wide and many cities and villages were profiting of this gift. In this regard, vivifying of this road will lead to grow the underserved urban and rural areas according to many tourist attractions of the cities and villages.
基金This study was supported by National Natural Science Foundation of China （No. 81373871 and No. 81473637）.
文摘This study aims to explore the effect and mechanism of Jiao-tai-wan （JTW） on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant （OR） rats with chronic partial sleep deprivation （PSD）. OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose （FPG）, fasting insulin （FINS）, homeostasis model assessment-insulin resistance （HOMA-IR） and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 （Cryl） and cryptochrome 2 （Cry2） in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B （NF-κB） p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3＇, 5＇-monophosphate （cAMP） and activity of vasodilator-stimulated phosphoprotein （VASP） in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042,81771353the Natural Science Foundation of Guangdong Province of China,No.S2013040016915+3 种基金the Science and Technology Program of Guangzhou City of China,No.201508020050,201604020003the Pearl River S&T Nova Program of Guangzhou,the Postdoctoral Foundation of China,No.BBK42913K09,201003345,BBH429151701a grant from the Hong Kong Scholar Program,Guangzhou University of TCM 2017 High Level University Construction Program,No.A1-AFD018171Z11096a grant from the Specialty Program of Guangdong Province Hospital of Traditional Chinese Medicine of China,No.YN2016MJ07,YN2015QN16,YN2015B2025
文摘Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 （NOX2） was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco＇s modified Eagle＇s medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen, species in astrocytes subjected to ischemia-＇reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine （8-OHdG）, 4-hydroxy-2-nonenal （4-HNE） and 3-nitrotyrosin （3-NT） in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin im- proved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.
基金the Natural Science Foundation of Jilin province:Investigation of the Regulatory Mechanism of Cognitive Function in Sleep-Deprived Rats Treated with Acupuncture based on the Rat Sarcoma Virus Oncogene/Rapidly Accelerated Fibrosarcoma/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase/Extracellular Signal-Regulated Kinase pathway(No.20210101222JC)。
文摘OBJECTIVE:To investigate the effects of acupuncture on learning and memory impairment,oxidative stress and autophagy induced by sleep depriv ation in rats,and to analyze the related mechanism.METHODS:Thirty Wistar rats were randomly divided into a normal group,sleep deprivation group and acupuncture group.The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation method.The Baihui(GV20),Shenmen(HT7)and Sanyinjiao(SP6)acupoints of rats were located to give electroacupuncture(density wave,frequency 20 Hz,intensity 1 mA)to maintain the needle feeling,and to keep the needle for 15min and continuous acupuncture for 7 d.The spatial learning and memory abilities of the rats were detected by the water maze test.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GPX)in the brain were detected by an assay kit,and the autophagy related proteins light chain 3 alpha(LC3A),light chain 3 beta(LC3B)and Beclin 1 and the activation of the protein kinase B(PKB/AKT)and mechanistic target of rapamycin(mTOR)signaling pathway in the rat's brain were detected by Western blotting.RESULTS:Compared with the normal group,the time spent in the target quadrant(P<0.05)and the number of times entering the target quadrant(P<0.05)in the rats of sleep deprivation group were significantly reduced,and the content of MDA was significantly increased(P<0.01),while the activities of SOD and GPX(P<0.01)in the brain were significantly decreased,and LC3AⅡ/Ⅰ,LC3BⅡ/Ⅰand Beclin 1 increased significantly(P<0.01),while pAKT(ser473)/AKT,p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70S6 decreased significantly(P<0.01).Compared with the sleep deprivation group,the time spent in the target quadrant and the times of entering the target quadrant(P<0.05)in the rats of acupuncture group after 7 d of treatment were significantly increased,Additionally,the content of MDA was significantly decreased(P<0.05),while the activities of SOD and GPX(P<0.05)in the brain were significantly increased.Moreover,the levels of LC3AⅡ/Ⅰ,LC3BⅡ/Ⅰand Beclin 1 decreased significantly(P<0.05),and that of pAKT(ser473)/AKT,p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70s6k increased significantly(P<0.05).CONCLUSION:Acupuncture can significantly improve the learning and memory damage caused by sleep deprivation and inhibit oxidative stress and autophagy,and its effect is related to the activation of AKT/mTOR signaling.
基金the National Natural Science Foundation of China, No. 30970956, 30570579
文摘The habenular nucleus （Hb） is an important structure that regulates the function of the pineal gland which may affect melatonin content in the pineal gland after sleep deprivation （SD）. In the present study, high performance liquid chromatography showed that the melatonin content in the pineal gland was significantly reduced, and y-aminobutyric acid content in the Hb was significantly increased after SD. Furthermore, the melatonin content in the pineal gland was markedly reduced after Hb lesion under normal sleep and SD conditions. Immunohistochemistry showed that the number of Fos-positive neurons was significantly decreased in the lateral and medial Hb after SD. The findings demonstrate that the reduction of melatonin in the pineal gland after SD is related to decreased activity of Hb neurons, and that the Hb can regulate sleep-wake rhythm by influencing melatonin secretion in the pineal gland.
基金Supported by the Research Council of Kermanshah University of Medical Sciences,Kermanshah,Iran for financial support(grant no.:990812).
文摘Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金Supported by the National Natural Science Foundation of China(No.81373871,81473637)
文摘Objective: To explore the effect and mechanism of Jiaotai Pill(交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation(PSD). Methods: Obesity resistant(OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide(LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin(Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes(Cry1 and Cry2) in the intestine were also determined. Results: The treatment of JTW significantly decreased LPS level in OR rats with PSD(P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting(P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. Conclusions: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.
基金National Natural Science Foundation of China,Grant/Award Numbers:31870981,82020108016Li Ka Shing Foundation,Grant/Award Numbers:2020LKSFG05D,2020LKSFG06CKey Disciplinary Projectof Clinical Medicine under the Guangdong High-Level University Development Program,Grant/Award Number:002-18120302。
文摘Background:Sleep deprivation causes hippocampal injury,manifesting as neuronal damage and learning-memory impairment.These negative effects may be associated with disturbance of hippocampal glutamate and water homeostasis,which induces excessive neuronal excitability.Five percent CO_(2) inhalation has been shown to suppress neuronal excitability.Here,we aimed to investigate whether 5%CO_(2) inhalation facilitates the recovery of hippocampal glutamate and water homeostasis,neuron morphology,and learning-memory ability in sleep-deprived rats.Methods:Thirty-six Sprague-Dawley female rats were randomly divided into three groups including normal sleep(Group 1,NS,n=12),sleep deprivation followed by sleep recovery(Group 2,SD+SR,n=12),sleep deprivation followed by sleep recovery and 5%CO_(2) inhalation(Group 3,SD+SR+CO_(2),n=12)by random number table.Each group was divided into two subgroups(n=6 each subgroup)for different experiments randomly by random number table.Results:We found that 5%CO_(2) inhalation facilitated the recovery of hippocampal glutamate concentration(7.549±0.310,8.716±0.463,and 7.493±0.281 mmol/L at Days 1,3,and 5 in Group 3,F 2,15=22.06,p<0.0001)and hippocampal apparent diffusion coefficient mean value(8.210±0.274,7.685±0.171,8.265±0.269 at Days 1,3,and 5 in Group 3,F 2,15=10.45,p=0.0014),enhanced expression level of astrocyte-specific membrane protein glutamate transporter-1,promoted the polarized distribution of aquaporin 4,reduced hippocampal neuronal damage and improved learning-memory ability in sleep-deprived rats.Conclusion:This study showed that 5%CO_(2) inhalation can serve as a novel strategy for alleviating sleep deprivation-induced hippocampal injury.
基金supported by the National Natural Science Foundation of China,No.31870977(to HYS)the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD)+2 种基金2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC)Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。
文摘Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
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.
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 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.
基金supported by the National Natural Science Foundation of China(82574916)the Joint Fund of Henan Province(232301420018).
文摘Objective This study aimed to investigate the protective effect and mechanism of Senkyunolide A(SenA)on oxygen-glucose deprivation/reoxygenation(OGD/R)-induced injury in mouse hippocampal neuronal HT22 cells,providing experimental evidence for elucidating the application of SenA in the prevention and treatment of cerebral ischemia–reperfusion injury.Methods An HT22 cell injury model was established using the OGD/R method and divided into the Control group,Model(OGD/R)group,Edaravone(EDA)group(OGD/R+EDA),and SenA group(OGD/R+SenA).Cell viability was detected by Cell counting kit-8(CCK-8)assay;live and dead cells were observed by Calcein AM/PI cell viability assay kit(Calcein-AM/PI)double staining;intracellular reactive oxygen species(ROS)levels were measured using the H2DCFDA(DCFH-DA)fluorescent probe;levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)were determined by biochemical kits;apoptosis rate was detected by flow cytometry;protein expression levels of Bcl-2-associated X protein(Bax),B-cell lymphoma 2(Bcl-2),and Cysteine-dependent aspartate-specific protease-3(Caspase-3)were measured by Western blot.Results Compared with the Control group,the OGD/R group showed significantly reduced cell viability(p<0.001),increased proportions of dead cells,ROS and MDA levels,and apoptosis rate(p<0.001),decreased SOD activity and GSH levels(p<0.05;p<0.001),significantly upregulated protein expression of Bax and Caspase-3(p<0.01;p<0.001),and downregulated Bcl-2 expression(p<0.001).Compared with the OGD/R group,both SenA and EDA significantly increased cell viability(p<0.001),reduced the proportion of dead cells,ROS and MDA levels,and apoptosis rate(p<0.001),upregulated SOD activity and GSH levels(p<0.01;p<0.001),downregulated protein expression of Bax and Caspase-3(p<0.01;p<0.001),and upregulated Bcl-2 expression(p<0.001).Conclusion SenA can alleviate OGD/R-induced neuronal injury by mitigating oxidative stress and inhibiting cell apoptosis.This study provides modern experimental evidence for the traditional theory of Chuanxiong in“promoting blood circulation,removing blood stasis,and unblocking brain collaterals,”and offers new insights for the prevention and treatment of ischemia–reperfusion brain injury with traditional Chinese medicine.
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Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT.The PubMed database was searched for studies published over the past 20 years.We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT.The primary outcome measure was the sexual function.Studies assessed sexual function using quality of life patient-reported outcome measures,which included sexual potency/activity evaluation.Information from 2947 patients was analyzed in this review.The median age of patients was 70 years.At baseline,a median of 49.9%(95%confidence interval[Cl]:49.1%-50.7%)of the patients reported being sexually active.At 6 months,12 months,and 2 years or later of ADT treatment,a median of 10.3%(95%Cl:10.2%-10.5%),8.9%(95%Cl:8.6%-9.2%),and 8.3%(95%Cl:8.2%-8.5%)of the patients reported being sexually active,respectively.Considering that half of the patients were sexually active at baseline,it seems probable that more than 10%of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT.In conclusion,despite the common belief that ADT eliminates sexual activity,this analysis found that approximately 1 in 10 men are sexually active when on ADT,and this proportion is likely increased in men who are sexually active before starting ADT.Attention to sexual activity should not be dismissed in men on ADT.
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Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.NRF-RS-2023-00237287.
文摘This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of night shifts and nega-tive cardiometabolic outcomes,such as elevated resting pulse rates and lowered levels of high-density lipoprotein cholesterol.These outcomes underscore the health risks linked to partial sleep deprivation,a common challenge in military environments.The editorial highlights the clinical significance of these findings,advocating for the implementation of targeted health interventions to mitigate these risks.Strategies such as structured sleep recovery programs and lifestyle modifications are recommended to improve the health management of military personnel engaged in nocturnal duties.By addressing these issues,military health management can better safeguard the well-being and operational readiness of its personnel.
