Modeling monocular form deprivation in rabbits using a simulated-cataract intraocular lens

AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2) thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2) into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2) were successfully constructed.The 0 SiO_(2) PSF was transparent,while the 10%wt SiO_(2) PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2) was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

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.

IMPACT de la déprivation sociale sur les difficultés psychosociales au décours d’un cancer pédiatrique:uneétude prospective IMPACT of the Social Deprivation on Psychosocial Difficulties of Pediatric Cancer Survivors:A Prospective Study

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.

Maternal sleep deprivation disrupts glutamate metabolism in offspring rats

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.

Regional deprivation and cause-specific mortality in Russian adults in 2006-2022

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.

Alterations of sleep deprivation on brain function:A coordinatebased resting-state functional magnetic resonance imaging metaanalysis

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.

Regulatory role of CREB/BDNF signaling pathway in acute sleep deprivation-induced anxiety-like behavior mice

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.

Intermittent androgen deprivation therapy in patients with prostate cancer: Connecting the dots

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.

ADJUSTING EFFECTS OF APPLICATION OF GARLIC PASTE AT SHNQU (神阙 CV8) ON THE CIRCADIAN RHYTHM OF BODY TEMPERATURE INDUCED BY SLEEP DEPRIVATION

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.

Enhancement of GABA_A Receptor-Mediated Inhibitory Postsynaptic Currents Induced by "Partial Oxygen-Glucose Deprivation"

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.

Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

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.

Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion

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.

IcarisideⅡ alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 celloxidative injury by activating Nrf2 / SIRT3signaling pathway

OBJECTIVE To investigate icariside(ICS)Ⅱ protects against PC12 cel damage induced by oxygen-glucose deprivation and reoxygenation and explore its mechanism.METHODS The oxidative stress injury model was induced by oxygen-glucose deprivation/reoxygenation(OGD/R) 2 h/24 h in PC12 cells.N-acetyl-lcysteine(NAC),a classical anti-oxidant,was used as positive control.Pharmacodynamic experimental study groups as follows:control,control+ICS Ⅱ50 μmol·L^(-1),OGD/R,OGD/R+ICSⅡ 12.5 μmol·L^(-1),OGD/R + ICS Ⅱ 25 μmol·L^(-1),OGD/R + ICS Ⅱ50 μmol·L^(-1),and OGD/R+NAC 100 μmol·L^(-1) groups.Cell viability and lactate dehydrogenase(LDH) leakage rate were measured by MTT assay and LDH ELISA kit,respectively.Moreover,reactive oxygen species(ROS) ELISA kit was used for detection of intracellular ROS generation,Mito-SOX fluorescence staining was used for detecting production of ROS in mitochondria and mitochondrial membrane potential(MMP)was detected by rhodamine 123 dye.In addition,PC12 cells apoptosis was detected by one-step TUNEL assay.Furthermore,the expressions of nuclear factor erythroid 2-related factors(Nrf2),Keap1,HO^(-1),NQO^(-1),silent information regulator 3(SIRT3),IDH2,Bax,Bcl-2 and caspase 3 were detected by Western blotting analysis.RESULTS The results of MTT and LDH assay showed that OGD/R reduced the cell viability and improved LDH release compared with the control or ICSⅡ 50 μmol·L^(-1) alone(P<0.01).Meanwhile,OGD/R not only increased intracellular and mitochondrial ROS generation,but also elevated the fluorescence intensity of TUNEL staining,at the same time,the MMP was declined when challenged by OGD/R.Furthermore,the Western blotting results showed that OGD/R induced the increase in the expression of cytoplasm-Nrf2,Keap1,Bax and cleaved-caspase 3 level,while the decrease in the expression of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).However,ICS Ⅱ significantly increased the viability of PC12 cells and reduced LDH leakage(P<0.01).Notably,ICS Ⅱ also suppressed ROS generation both in the intracellular and mitochondria,as well as restored MMP.It was also worthy to note that ICS Ⅱ decreased the expressions of cytoplasmNrf2,Keap1,Bax and the level of cleaved-caspase3,whereas,it increased the expressions of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).CONCLUSION ICSⅡ reduced OGD/Rinduced oxidative damage in PC12 cells under the laboratory conditions,and its underlying mechanism may be related to the regulation of Nrf2/SIRT3 signaling pathway.

Relationship between monocularly deprivation and amblyopia rats and visual system development

Objective:To explore the changes of lateral geniculate body and visual cortex in monocular strabismus and form deprived amblyopic rat,and visual development plastic stage and visual plasticity in adult rats.Methods:A total of 60 SD rats ages 13 d were randomly divided into A,B,C three groups with 20 in each group,group A was set as the normal control group without any processing,group B was strabismus amblyopic group,using the unilateral extraocular rectus resection to establish the strabismus amblyopia model,group C was monocular form deprivation amblyopia group using unilateral eyelid edge resection+lid suture.At visual developmental early phase(P2S),meta phase(P3S),late phase(P45)and adult phase(P120),the lateral geniculate body and visual cortex area 17 of five rats in each group were exacted for C-fos Immunocytochemistry.Neuron morphological changes in lateral geniculate body and visual cortex was observed,the positive neurons differences of C-fos expression induced by light stimulation was measured in each group,and the condition of radiation development of P120 amblyopic adult rats was observed.Results:In groups B and C,C-fos positive cells were significantly lower than the control group at P25(P<0.05),there was no statistical difference of C-fos protein positive cells between group B and group A(P>0.05),C-fos protein positive cells level of group B was significantly lower than that of group A(P<0.05).The binoculus C-fos protein positive cells level of groups B and C were significantly higher than that of control group at P35,P4S and P120 with statistically significant differences(P<0.05).Conclusions:The increasing of C-fos expression in geniculate body and visual cortex neurons of adult amblyopia suggests the visual cortex neurons exist a certain degree of visual plasticity.

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Prostate cancer （PCa） is the most common visceral malignancy in men with androgen deprivation therapy （ADT） the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data （up to 2 years） for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

Sleep deprivation increase the expression of inducible heat shock protein 70 in rat gastric mucosa

AIM: To investigate if sleep deprivation is able to increase the expression of inducible heat shock protein 70 in gastric mucosa and its possible role in mucosal defense. METHODS: Rats for sleep disruption were placed inside a computerized rotating drum, gastric mucosa was taken from rats with 1, 3 and 7d sleep deprivation. RT-PCR, immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70. Ethanol (500mL.L(-1), i.g.) was used to induce gastric mucosa damage. RESULTS: RT-PCR, Western blotting and immunostaining confirmed that the sleep deprivation as a stress resulted in significantly greater expression of inducible heat shock protein 70 in gastric mucosa of rats. After the 500mL.L(-1) ethanol challenge, the ulcer area found in the rats with 7d sleep deprivation (19.15 +/- 4.2)mm(2) was significantly lower (P【0.01) than the corresponding control (53.7 +/- 8.1) mm(2). CONCLUSION: Sleep deprivation as a stress, in addition to lowering the gastric mucosal barrier, is able to stimulate the expression of inducible heat shock protein 70 in gastric mucosa of rats, the heat shock protein 70 may play an important role in gastric mucosal protection.

Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats

Maternal sleep deprivation(MSD)is a global public health problem that affects the physical and mental development of pregnant women and their newborns.The latest research suggests that sleep deprivation(SD)disrupts the gut microbiota,leading to neuroinflammation and psychological disturbances.However,it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns.In the present study,MSD was performed on pregnant SpragueDawley rats in the third trimester of pregnancy(gestational days 15-21),after which intestinal contents and brain tissues were collected from offspring at different postnatal days(P1,P7,P14,and P56).Based on microbial profiling,microbial diversity and richness increased in pregnant rats subjected to MSD,as reflected by the significant increase in the phylum Firmicutes.In addition,microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring.Furthermore,quantitative real-time polymerase chain reaction(q RT-PCR)and enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of proinflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factorα(TNF-α)were significantly higher in the MSD offspring at adulthood(P56)than in the control group.Through Spearman correlation analysis,IL-1βand TNF-αwere also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56,which may determine the microbiota-host interactions in MSDrelated neuroinflammation.Collectively,these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota,leading to neuroinflammation in MSD offspring.Therefore,understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.

Curcumin pretreatment and post-treatment both improve the antioxidative ability of neurons with oxygen-glucose deprivation

Recent studies have shown that induced expression of endogenous antioxidative enzymes thr- ough activation of the antioxidant response element/nuclear factor erythroid 2-related factor 2 （Nrf2） pathway may be a neuroprotective strategy. In this study, rat cerebral cortical neurons cultured in vitro were pretreated with 10 ktM curcumin or post-treated with 5 pM curcumin, respectively before or after being subjected to oxygen-glucose deprivation and reoxygenation for 24 hours. Both pretreatment and post-treatment resulted in a significant decrease of cell injury as indicated by propidium iodide/Hoechst 33258 staining, a prominent increase of Nrf2 protein expression as indicated by western blot analysis, and a remarkable increase of protein expression and enzyme activity in whole cell lysates of thioredoxin before ischemia, after ischemia, and after reoxygenation. In addition, post-treatment with curcumin inhibited early DNA/RNA oxidation as indicated by immunocytochemistry and increased nuclear Nrf2 protein by inducing nuclear accumulation of Nrf2. These findings suggest that curcumin activates the expression of thi- oredoxin, an antioxidant protein in the Nrf2 pathway, and protects neurons from death caused by oxygen-glucose deprivation in an in vitro model of ischemia/reperfusion. We speculate that pharmacologic stimulation of antioxidant gene expression may be a promising approach to neu- roprotection after cerebral ischemia.

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

Protective mechanisms of micro RNA-27a against oxygen-glucose deprivation-induced injuries in hippocampal neurons

Hypoxic injuries during fetal distress have been shown to cause reduced expression of micro RNA-27a（mi R-27a）,which regulates sensitivity of cortical neurons to apoptosis.We hypothesized that miR-27 a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1,an important transcription factor for regulating the oxidative stress response.miR-27 a mimic was transfected into hippocampal neurons to overexpress miR-27 a.Results showed increased hippocampal neuronal viability and decreased caspase-3 expression.The luciferase reporter gene system demonstrated that mi R-27 a directly binded to FOXO1 3′UTR in hippocampal neurons and inhibited FOXO1 expression,suggesting that FOXO1 was the target gene for mi R-27 a.These findings confirm that mi R-27 a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries.The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.