Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we id...Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.展开更多
BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported result...BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.展开更多
Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of...Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.展开更多
Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations....Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.展开更多
In the developing world,vulnerable communities often lack access to regular income sources to cope with unforeseen events.Recent advancements in financial technology have enabled microcredit to be delivered via digita...In the developing world,vulnerable communities often lack access to regular income sources to cope with unforeseen events.Recent advancements in financial technology have enabled microcredit to be delivered via digital platforms.Although digital credit may quicken remote access to consumer credit without the need for collateral,little is known about its contribution to the welfare of underserved communities.This study examines the effects of local digital lending development on deprivation and explores the implications of these effects on rural inhabitants.The results show a negative association between local digital lending development and food deprivation on one hand and health deprivation on the other.The evidence suggests that local digital lending development can reduce the probability of food and health deprivation.Furthermore,the evidence reveals that inhabitants of rural communities benefit more from digital lending development.This study recommends the decentralization of financial inclusion policies as a pathway to promote digital lending at the local level.展开更多
Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 ce...Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGDtreated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside.Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside.Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.展开更多
AIM:To construct an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R)induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion(I/R)injury in 661W cells and the...AIM:To construct an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R)induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion(I/R)injury in 661W cells and the protective effect of ginsenoside Rg1.METHODS:The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro.Apoptosis,intracellular reactive oxygen species(ROS)levels and superoxide dismutase(SOD)levels were measured at different time points during the reperfusion injury process.The injury model was pretreated with graded concentrations of ginsenoside Rg1.Real-time polymerase chain reaction(PCR)was used to measure the expression levels of cytochrome C(cyt C)/B-cell lymphoma-2(Bcl2)/Bcl2 associated protein X(Bax),heme oxygenase-1(HO-1),caspase9,nuclear factor erythroid 2-related factor 2(nrf2),kelch-like ECH-associated protein 1(keap1)and other genes.Western blot was used to detect the expression of nrf2,phosphorylated nrf2(pnrf2)and keap1 protein levels.RESULTS:Compared to the untreated group,the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased(P<0.01).Additionally,the ROS content increased and SOD levels decreased significantly(P<0.01).In contrast,treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na_(2)S_(2)O_(4)treated group(P<0.01).Moreover,Rg1 reduced the levels of caspase3,caspase9,and cyt C,while increasing the Bcl2/Bax level.These differences were all statistically significant(P<0.05).Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment,however,Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na_(2)S_(2)O_(4)treated group(P<0.001).CONCLUSION:The OGD/R process is induced in 661W cells using Na_(2)S_(2)O_(4).Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway.These results suggest a potential protective effect of Rg1 against retinal I/R injury.展开更多
Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25...Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25 mmol/L,50 mmol/L,100 mmol/L,200 mmol/L,400 mmol/L)groups,and treated with corresponding concentrations of D-galactose for 48 h.The changes of cell morphology,β-galactosidase,the cell morphology,β-galactosidase activity by microscopic observation,cell proliferation rate by EdU kit and cell survival rate by CCK-8 assay were used to determine the decaying concentration of D-galactose and to establish the senescence model.The senescent SH-SY5Y cells were randomly divided into control group(oxygen glucose deprivation without treatment group),oxygen glucose deprivation treatment(0.5 h,1 h,1.5 h,2 h)group,followed by re-glucose reoxygenation for 24 h,and CCK-8 assay for the survival rate of senescent SH-SY5Y cells.Results:There were no significant changes in cell morphology and β-gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group(P>0.05),cytosolic hypertrophy was seen in the cells of the 100 mmol/L group,chromatin fixation in the cells of the 200 mmol/L group,and massive vacuolization in the cells of the 400 mmol/L group;the positive rate ofβ-galactosidase staining in the cells of the(100-400 mmol/L)group was significantly higher compared with the control group(P<0.05),with little difference between the 100 mmol/L and 200 mmol/L groups(P>0.05);the cell proliferation ability of the(100-400 mmol/L)group was significantly decreased in a concentration-dependent manner(P<0.05);the cell survival rate was decreased in a concentration-dependent manner(P<0.05),with IC_(50) between 100 mmol/L and 200 mmol/L.The survival of senescent SH-SY5Y cells showed a time-dependent decrease in oxygen-glucose deprivation(P<0.05),with an IC_(50) close to 1 h.Conclusion:D-gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50%of senescent SH-SY5Y cells,and oxygen glucose deprivation of senescent SH-SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells with a survival rate close to 50%.展开更多
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 ...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.展开更多
Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic sys...Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the weli-descrihed actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.展开更多
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 resul...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.展开更多
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 i...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 7 d sleep deprivation. RT-PCR,immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70.Ethanol (500 mL@ L 1, I.g.) was used to induce gastric muceea 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 7 d sleep deprivation (19.15 ± 4.2) mm2 was significantly lower (P<0.01) than the corresponding control (53.7 ± 8.1) mm2.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.展开更多
Aim: To evaluate the effect of androgen deprivation therapy (ADT) on bone mineral density (BMD) in prostate cancer patients. Methods: Forty-nine prostate cancer patients with their BMD determined were divided into two...Aim: To evaluate the effect of androgen deprivation therapy (ADT) on bone mineral density (BMD) in prostate cancer patients. Methods: Forty-nine prostate cancer patients with their BMD determined were divided into two groups: the non-treated group included 21 patients before the commencement of ADT and the treated group, 28 patients, who had received ADT for more than 1 year. BMD was measured by dual energy X-ray absorptiometry (DEXA) in the lumbar spine (L2-4) and femoral neck. Results: Thirteen (62 %) non-treated and 23 (82 %) treated patients fulfilled the BMD criteria for osteopenia or osteoporosis. Z scores for age-matched control in lumbar spine and femoral neck were -0.9 ± 0.7 and -0.6 ± 0.5, respectively, in the treated group, and -1.8 ± 1.1 and-1.6 ± 1.0 , respectively, in the non-treated group, the differences between the two groups were highly significant (P<0.01). Conclusion: Prostate cancer patients who received ADT for more than 1 year had a significantly lower BMD in the lumbar spine and femoral neck than those before the beginning of ADT.展开更多
This study was performed to assess serum testosterone alterations induced by paradoxical sleep deprivation (PSD) and to verify their attenuation during sleep recovery (SR) based on different durations and ages. Wi...This study was performed to assess serum testosterone alterations induced by paradoxical sleep deprivation (PSD) and to verify their attenuation during sleep recovery (SR) based on different durations and ages. Wistar male rats aged 12 weeks for the younger group and 20 weeks for the elder group were randomly distributed into one of the following groups: a control group (cage and platform), 3-day SD, 5-day SD, 7-day SD, 1-day SR, 3-day SR and 5-day SR groups. For PSD, the modified multiple platform method was used to specifically limit rapid eye movement (REM) sleep. Differences in the testosterone and luteinizing hormone levels between the younger group and the elder group according to duration of PSD and SR recovery were analysed. Testosterone continued to fall during the sleep deprivation period in a time-dependent manner in both the younger (P=-0.001, correlation coefficient r=-0.651) and elder groups (P=0.001, correlation coefficient r=-0.840). The elder group showed a significantly lower level of testosterone compared with the younger group after PSD. Upon SR after 3 days of PSD, the testosterone level continued to rise for 5 days after sleep recovery in the younger group (P=0.013), whereas testosterone concentrations failed to recover until day 5 in the elder group. PSD caused a more detrimental effect on serum testosterone in the elder group compared to the younger group with respect to decreases in luteinizing hormone (LH) levels. The replenishment of serum testosterone level was prohibited in the elder group suggesting that the effects of SD/SR may be age-dependent. The mechanism by which SD affects serum testosterone and how age may modify the process are still unclear.展开更多
INTRODUCTIONStress has been shown to induce gastric mucosallesions and lower the effectiveness of the mucosa asa barrier.In rats,gastric ulcers can beproduced by cold-restraint stress and it isfrequently employed as a...INTRODUCTIONStress has been shown to induce gastric mucosallesions and lower the effectiveness of the mucosa asa barrier.In rats,gastric ulcers can beproduced by cold-restraint stress and it isfrequently employed as a model for the study of themechanisms of stress on ulcer formation.Cold-restraint stress however is not normally展开更多
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 effectivene...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.展开更多
Prostate cancer is one of the most common malignancies in men. Previous research has determined that androgen deprivation therapy (ADT) may be accompanied by an unfavourable metabolic profile. In this prospective st...Prostate cancer is one of the most common malignancies in men. Previous research has determined that androgen deprivation therapy (ADT) may be accompanied by an unfavourable metabolic profile. In this prospective study, 133 men were recruited, including 46 prostate cancer patients who had undergone bilateral orchiectomy and been on flutamide (the ADT group), 37 men with prostate cancer who had undergone radical prostatectomy (the non-ADT group) and 50 normal control subjects (the control group). All subjects were followed for at least 12 months. From baseline to 3 months, men in the ADT group had increased levels of fasting serum insulin and low-density lipoprotein compared to the other two groups (P〈0.05). No obvious changes were found in the other parameters (P〉0.05). After 12 months, men in the ADT group had increased levels of waist circumference, fasting serum insulin and glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein compared to the other two groups (P〈0.05). Additionally, the morbidity rate of metabolic syndrome in the ADT group was higher (P〈0.05) compared to the other two groups. ADT through surgical castration for men with prostate cancer may be associated with unfavourable metabolic changes. The benefits of the therapy should be balanced prudently against these risks.展开更多
AIM: To investigate the role of activating transcription factor 4(ATF4) in glucose deprivation(GD) induced colorectal cancer(CRC) drug resistance and the mechanism involved.METHODS: Chemosensitivity and apoptosis were...AIM: To investigate the role of activating transcription factor 4(ATF4) in glucose deprivation(GD) induced colorectal cancer(CRC) drug resistance and the mechanism involved.METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RTPCR and Western blot were used to detect the mR NA and protein expression of drug resistance gene 1(MDR1), respectively.RESULTS: GD protected CRC cells from drug-induced apoptosis(oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug resensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.展开更多
Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including d...Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hormonal therapy of hot flashes has been shown to be effective, multiple non-hormonal medications and treatment methods have also been developed. This article reviews current options for the treatment of hot flashes in patients taking ADT.展开更多
Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotect...Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.展开更多
基金National Natural Science Foundation of China(81870850)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0322)。
文摘Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.
文摘BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.
基金National Natural Science Foundation of China,Nos.81771160 (to ZZ),81671060 (to CC),31970973 (to JW),21921004 (to FX)Translational Medicine and In terdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,No.ZNJC201934 (to ZZ)。
文摘Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.
基金supported by the National Natural Science Foundation of China,No.81973501the Natural Science Foundation of Shandong Province,No.ZR2019MH009(both to YLG).
文摘Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.
文摘In the developing world,vulnerable communities often lack access to regular income sources to cope with unforeseen events.Recent advancements in financial technology have enabled microcredit to be delivered via digital platforms.Although digital credit may quicken remote access to consumer credit without the need for collateral,little is known about its contribution to the welfare of underserved communities.This study examines the effects of local digital lending development on deprivation and explores the implications of these effects on rural inhabitants.The results show a negative association between local digital lending development and food deprivation on one hand and health deprivation on the other.The evidence suggests that local digital lending development can reduce the probability of food and health deprivation.Furthermore,the evidence reveals that inhabitants of rural communities benefit more from digital lending development.This study recommends the decentralization of financial inclusion policies as a pathway to promote digital lending at the local level.
基金supported by the Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(2021ZB027,2023ZL267)Zhejiang Medical and Health Platform Project of China(2019KY002,2019RC092).
文摘Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGDtreated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside.Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside.Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.
基金Supported by Natural Science Foundation of Guangdong Province(No.2021A1515010513)。
文摘AIM:To construct an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R)induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion(I/R)injury in 661W cells and the protective effect of ginsenoside Rg1.METHODS:The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro.Apoptosis,intracellular reactive oxygen species(ROS)levels and superoxide dismutase(SOD)levels were measured at different time points during the reperfusion injury process.The injury model was pretreated with graded concentrations of ginsenoside Rg1.Real-time polymerase chain reaction(PCR)was used to measure the expression levels of cytochrome C(cyt C)/B-cell lymphoma-2(Bcl2)/Bcl2 associated protein X(Bax),heme oxygenase-1(HO-1),caspase9,nuclear factor erythroid 2-related factor 2(nrf2),kelch-like ECH-associated protein 1(keap1)and other genes.Western blot was used to detect the expression of nrf2,phosphorylated nrf2(pnrf2)and keap1 protein levels.RESULTS:Compared to the untreated group,the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased(P<0.01).Additionally,the ROS content increased and SOD levels decreased significantly(P<0.01).In contrast,treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na_(2)S_(2)O_(4)treated group(P<0.01).Moreover,Rg1 reduced the levels of caspase3,caspase9,and cyt C,while increasing the Bcl2/Bax level.These differences were all statistically significant(P<0.05).Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment,however,Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na_(2)S_(2)O_(4)treated group(P<0.001).CONCLUSION:The OGD/R process is induced in 661W cells using Na_(2)S_(2)O_(4).Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway.These results suggest a potential protective effect of Rg1 against retinal I/R injury.
基金This is supported by the Youth Science Foundation of Guangxi Medical University(GXMUYSF202127)。
文摘Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25 mmol/L,50 mmol/L,100 mmol/L,200 mmol/L,400 mmol/L)groups,and treated with corresponding concentrations of D-galactose for 48 h.The changes of cell morphology,β-galactosidase,the cell morphology,β-galactosidase activity by microscopic observation,cell proliferation rate by EdU kit and cell survival rate by CCK-8 assay were used to determine the decaying concentration of D-galactose and to establish the senescence model.The senescent SH-SY5Y cells were randomly divided into control group(oxygen glucose deprivation without treatment group),oxygen glucose deprivation treatment(0.5 h,1 h,1.5 h,2 h)group,followed by re-glucose reoxygenation for 24 h,and CCK-8 assay for the survival rate of senescent SH-SY5Y cells.Results:There were no significant changes in cell morphology and β-gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group(P>0.05),cytosolic hypertrophy was seen in the cells of the 100 mmol/L group,chromatin fixation in the cells of the 200 mmol/L group,and massive vacuolization in the cells of the 400 mmol/L group;the positive rate ofβ-galactosidase staining in the cells of the(100-400 mmol/L)group was significantly higher compared with the control group(P<0.05),with little difference between the 100 mmol/L and 200 mmol/L groups(P>0.05);the cell proliferation ability of the(100-400 mmol/L)group was significantly decreased in a concentration-dependent manner(P<0.05);the cell survival rate was decreased in a concentration-dependent manner(P<0.05),with IC_(50) between 100 mmol/L and 200 mmol/L.The survival of senescent SH-SY5Y cells showed a time-dependent decrease in oxygen-glucose deprivation(P<0.05),with an IC_(50) close to 1 h.Conclusion:D-gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50%of senescent SH-SY5Y cells,and oxygen glucose deprivation of senescent SH-SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells with a survival rate close to 50%.
文摘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.
文摘Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the weli-descrihed actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.
文摘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.
文摘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 7 d sleep deprivation. RT-PCR,immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70.Ethanol (500 mL@ L 1, I.g.) was used to induce gastric muceea 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 7 d sleep deprivation (19.15 ± 4.2) mm2 was significantly lower (P<0.01) than the corresponding control (53.7 ± 8.1) mm2.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.
文摘Aim: To evaluate the effect of androgen deprivation therapy (ADT) on bone mineral density (BMD) in prostate cancer patients. Methods: Forty-nine prostate cancer patients with their BMD determined were divided into two groups: the non-treated group included 21 patients before the commencement of ADT and the treated group, 28 patients, who had received ADT for more than 1 year. BMD was measured by dual energy X-ray absorptiometry (DEXA) in the lumbar spine (L2-4) and femoral neck. Results: Thirteen (62 %) non-treated and 23 (82 %) treated patients fulfilled the BMD criteria for osteopenia or osteoporosis. Z scores for age-matched control in lumbar spine and femoral neck were -0.9 ± 0.7 and -0.6 ± 0.5, respectively, in the treated group, and -1.8 ± 1.1 and-1.6 ± 1.0 , respectively, in the non-treated group, the differences between the two groups were highly significant (P<0.01). Conclusion: Prostate cancer patients who received ADT for more than 1 year had a significantly lower BMD in the lumbar spine and femoral neck than those before the beginning of ADT.
文摘This study was performed to assess serum testosterone alterations induced by paradoxical sleep deprivation (PSD) and to verify their attenuation during sleep recovery (SR) based on different durations and ages. Wistar male rats aged 12 weeks for the younger group and 20 weeks for the elder group were randomly distributed into one of the following groups: a control group (cage and platform), 3-day SD, 5-day SD, 7-day SD, 1-day SR, 3-day SR and 5-day SR groups. For PSD, the modified multiple platform method was used to specifically limit rapid eye movement (REM) sleep. Differences in the testosterone and luteinizing hormone levels between the younger group and the elder group according to duration of PSD and SR recovery were analysed. Testosterone continued to fall during the sleep deprivation period in a time-dependent manner in both the younger (P=-0.001, correlation coefficient r=-0.651) and elder groups (P=0.001, correlation coefficient r=-0.840). The elder group showed a significantly lower level of testosterone compared with the younger group after PSD. Upon SR after 3 days of PSD, the testosterone level continued to rise for 5 days after sleep recovery in the younger group (P=0.013), whereas testosterone concentrations failed to recover until day 5 in the elder group. PSD caused a more detrimental effect on serum testosterone in the elder group compared to the younger group with respect to decreases in luteinizing hormone (LH) levels. The replenishment of serum testosterone level was prohibited in the elder group suggesting that the effects of SD/SR may be age-dependent. The mechanism by which SD affects serum testosterone and how age may modify the process are still unclear.
基金the CRCG grant from the University of Hong Kong.
文摘INTRODUCTIONStress has been shown to induce gastric mucosallesions and lower the effectiveness of the mucosa asa barrier.In rats,gastric ulcers can beproduced by cold-restraint stress and it isfrequently employed as a model for the study of themechanisms of stress on ulcer formation.Cold-restraint stress however is not normally
文摘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.
文摘Prostate cancer is one of the most common malignancies in men. Previous research has determined that androgen deprivation therapy (ADT) may be accompanied by an unfavourable metabolic profile. In this prospective study, 133 men were recruited, including 46 prostate cancer patients who had undergone bilateral orchiectomy and been on flutamide (the ADT group), 37 men with prostate cancer who had undergone radical prostatectomy (the non-ADT group) and 50 normal control subjects (the control group). All subjects were followed for at least 12 months. From baseline to 3 months, men in the ADT group had increased levels of fasting serum insulin and low-density lipoprotein compared to the other two groups (P〈0.05). No obvious changes were found in the other parameters (P〉0.05). After 12 months, men in the ADT group had increased levels of waist circumference, fasting serum insulin and glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein compared to the other two groups (P〈0.05). Additionally, the morbidity rate of metabolic syndrome in the ADT group was higher (P〈0.05) compared to the other two groups. ADT through surgical castration for men with prostate cancer may be associated with unfavourable metabolic changes. The benefits of the therapy should be balanced prudently against these risks.
基金Supported by National Natural Science Foundation of China,No.81000867,No.81272299,No.81301784 and No.81301920Natural Science Foundation of Jiangsu Province,No.BK20150004 and No.BK20151108+3 种基金the Fundamental Research Funds for the Central Universities,No.NOJUSRP51619BMedical Key Professionals Program of Jiangsu Province,No.RC2011031"333" Talents Project of Jiangsu ProvinceHospital Management Center of Wuxi,No.YGZXM1524
文摘AIM: To investigate the role of activating transcription factor 4(ATF4) in glucose deprivation(GD) induced colorectal cancer(CRC) drug resistance and the mechanism involved.METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RTPCR and Western blot were used to detect the mR NA and protein expression of drug resistance gene 1(MDR1), respectively.RESULTS: GD protected CRC cells from drug-induced apoptosis(oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug resensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.
文摘Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hormonal therapy of hot flashes has been shown to be effective, multiple non-hormonal medications and treatment methods have also been developed. This article reviews current options for the treatment of hot flashes in patients taking ADT.
基金supported in part by the National Natural Science Foundation of China,No.81573644(to LMH),81573733(to SWX)the Tianjin 131 Innovative Team Project,China(to HW)+5 种基金the National Major Science and Technology Project of China,No.2012ZX09101201-004(to SWX)the Science and Technology Plan Project of Tianjin of China,No.16PTSYJC00120(to LMH)the Applied Foundation and Frontier Technology Research Program of Tianjin of China(General Project),No.14JCYBJC28900(to SXW)the National International Science and Technology Cooperation Project of China,No.2015DFA30430(to HW)the Key Program of the Natural Science Foundation of Tianjin of China,No.16ICZDJC36300(to HW)the Scientific Research and Technology Development Plan Project of Guangxi Zhuang Autonomous Region of China,No.14125008-2-5(to SXW)
文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.