Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature ...Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.展开更多
Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hy...Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hyperoxia exposure, and to unravel the molecular mechanisms of developing brain injury induced by normobaric hyperoxia. Methods: Eight neonatal Sprague-Dawley rats at postnatal 1 day were divided equally between a control group and an experimental group, followed by 24-hour exposure to 21% oxygen and (95 ± 5) % oxygen, respectively. Total RNAs were extracted from the rat hippocampus. Three samples were randomly selected from each group to detect differentially expressed mRNA profiles using the affymetrix GeneChip Rat Genome 230 2.0 Array. Differentially expressed miRNA profiles were determined by miRNA enrichment analysis. The starBase software was applied to predict target genes abundantly expressed in the hippocampus, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for bioinformatics analysis. Results: Microarray analysis revealed 681 differentially expressed miRNAs in the neonatal rat hippocampus after normobaric hyperoxia exposure. Only one miRNA, miR-489-5p, was significantly upregulated (P Mdfic. The other 680 miRNAs were significantly downregulated (P P Gjb6 and Bnc2. KEGG analysis indicated that differentially expressed miRNAs were closely related to multiple signaling pathways. Conclusions: Differentially expressed miRNA profiles in the neonatal rat hippocampus after normobaric hyperoxia exposure may be involved in the physiopathological processes of developmental midbrain injury induced by normobaric hyperoxia.展开更多
Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function....Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.展开更多
BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(H...BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.展开更多
Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocam...Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.展开更多
Objective To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat.Methods Experiments were performed on 184 male Wistar rats(three exposure groups and a sham group).Mi...Objective To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat.Methods Experiments were performed on 184 male Wistar rats(three exposure groups and a sham group).Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5,5,and 10 mW/cm2.Learning and memory abilities were assessed by Morris water maze.High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus.Hippocampal structures were observed by histopathological analysis.Results Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d,14 d,and 1 m in all three microwave exposure groups.Neurotransmitter concentrations of four amino acids(glutamate,aspartic acid,glycine,and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group.There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups.Further,mitochondria became swollen and cristae were disordered.The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles.Conclusion These data suggest that the hippocampus can be injured by long-term microwave exposure,which might result in impairment of cognitive function due to neurotransmitter disruption.展开更多
Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity imp...Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (CaZ+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.展开更多
Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four grou...Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four groups(25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 m W/cm^2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram(EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor(NMDAR) subunits(NR1, NR2 A, and NR2 B), c AMP responsive element-binding protein(CREB) and phosphorylated CREB(p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. Results The rats in the 10 and 30 m W/cm^2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 m W/cm^2 group had increased expressions of NR2 A and NR2 B and decreased levels of CREB and p-CREB. Conclusion Shortwave exposure(27 MHz, with an average power density of 10 and 30 m W/cm^2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.展开更多
BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study...BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively.CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.展开更多
Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, pr...Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.展开更多
Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with p...Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.展开更多
Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male ...Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results: The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion: The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.展开更多
Objective The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus. Methods SD rats in the experimental group were exposed to 140 d B(8 Hz...Objective The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus. Methods SD rats in the experimental group were exposed to 140 d B(8 Hz) infrasound for 2 h per day for 3 days. The morphology of the hippocampus was examined by transmission electronic microscopic(TEM). Cell apoptosis was observed by TUNEL staining at 0 h, 24 h, 48 h, and 2 w after exposure. HSP70 expression was detected by immunohistochemistry(IHC) and Western blotting(WB). Results TEM showed that hippocampus was significantly damaged by exposure, and exhibited recovery 1 week after exposure. The TUNEL data showed that neuronal apoptosis after exposure was significantly higher than in the control rats at 24 h and 48 h, and the apoptotic cells decreased one week after exposure. IHC and WB showed HSP70 expression was significantly higher in the exposed rats, peaked at 24 h. Conclusion Exposure to 140 d B(8 Hz) infrasound for 2 h per day for 3 days appeared to induce damage to the hippocampus of rats, based on changes in ultrastructure and increased cell apoptosis. However, recovery from the damage occurred overtime. HSP70 expression also increased after the exposure and decreased by 48 h.展开更多
BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pa...BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: D450 values of telomerase activity were 0.446 +/- 0.2700 in pancreatic cancer and 0.041 +/- 0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.展开更多
Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangl...Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.展开更多
Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-...Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovadectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.展开更多
基金supported by the National Natural Science Foundation of China (No. U20A20371)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (No. D171100006517004)+2 种基金Beijing Municipal Administration of Hospitals’ Youth Program (QML20191103)Clinical Medicine Plus X-Young Scholars Project, Peking Universitythe Fundamental Research Funds for the Central Universities and the Science Foundation of Peking University Cancer Hospital。
文摘Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
文摘Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hyperoxia exposure, and to unravel the molecular mechanisms of developing brain injury induced by normobaric hyperoxia. Methods: Eight neonatal Sprague-Dawley rats at postnatal 1 day were divided equally between a control group and an experimental group, followed by 24-hour exposure to 21% oxygen and (95 ± 5) % oxygen, respectively. Total RNAs were extracted from the rat hippocampus. Three samples were randomly selected from each group to detect differentially expressed mRNA profiles using the affymetrix GeneChip Rat Genome 230 2.0 Array. Differentially expressed miRNA profiles were determined by miRNA enrichment analysis. The starBase software was applied to predict target genes abundantly expressed in the hippocampus, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for bioinformatics analysis. Results: Microarray analysis revealed 681 differentially expressed miRNAs in the neonatal rat hippocampus after normobaric hyperoxia exposure. Only one miRNA, miR-489-5p, was significantly upregulated (P Mdfic. The other 680 miRNAs were significantly downregulated (P P Gjb6 and Bnc2. KEGG analysis indicated that differentially expressed miRNAs were closely related to multiple signaling pathways. Conclusions: Differentially expressed miRNA profiles in the neonatal rat hippocampus after normobaric hyperoxia exposure may be involved in the physiopathological processes of developmental midbrain injury induced by normobaric hyperoxia.
基金supported by grant PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by"ERDF A way of making Europe"(to RL)supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/21/180501/000064)+3 种基金Universidad de Castilla-La Mancha (2023-GRIN-34187)(to RL).Grant PID201 9-104921RB-I00/MCI/AEI/10.13039/501100011033 (to AGO)the Foundation for Applied Medical Research,the University of Navarra (Pamplona,Spain)for financial supporthe Asociación de Amigos of the University of Navarra for the grant (to SB)Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha (to AMB)
文摘Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.
文摘BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.
基金This work was supported by the National Nature Science Foundation of China (No.30470554)the National Basic Research Development Program of China(No.2003CB515404).
文摘Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.
基金supported by the National Natural Science Foundation of China (No. 30901169)
文摘Objective To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat.Methods Experiments were performed on 184 male Wistar rats(three exposure groups and a sham group).Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5,5,and 10 mW/cm2.Learning and memory abilities were assessed by Morris water maze.High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus.Hippocampal structures were observed by histopathological analysis.Results Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d,14 d,and 1 m in all three microwave exposure groups.Neurotransmitter concentrations of four amino acids(glutamate,aspartic acid,glycine,and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group.There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups.Further,mitochondria became swollen and cristae were disordered.The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles.Conclusion These data suggest that the hippocampus can be injured by long-term microwave exposure,which might result in impairment of cognitive function due to neurotransmitter disruption.
基金supported by the National Natural Science Foundation of China(No.81172620)
文摘Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (CaZ+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.
基金supported by the National Natural Science Fund [No.31570847]the fund organization had no role in the design or conduct of this research
文摘Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four groups(25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 m W/cm^2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram(EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor(NMDAR) subunits(NR1, NR2 A, and NR2 B), c AMP responsive element-binding protein(CREB) and phosphorylated CREB(p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. Results The rats in the 10 and 30 m W/cm^2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 m W/cm^2 group had increased expressions of NR2 A and NR2 B and decreased levels of CREB and p-CREB. Conclusion Shortwave exposure(27 MHz, with an average power density of 10 and 30 m W/cm^2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.
基金supported by a grant from JEIL Pharmaceuticals (Seoul, Korea)
文摘BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively.CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.
基金supported by a grant from the National Key Specialty Construction Project in China in 2012,No.[2012]650
文摘Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.
基金funded by key Technology Projects in Hainan Province (Grant No.090209.zdxm2010043)
文摘Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.
文摘Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results: The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion: The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.
文摘Objective The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus. Methods SD rats in the experimental group were exposed to 140 d B(8 Hz) infrasound for 2 h per day for 3 days. The morphology of the hippocampus was examined by transmission electronic microscopic(TEM). Cell apoptosis was observed by TUNEL staining at 0 h, 24 h, 48 h, and 2 w after exposure. HSP70 expression was detected by immunohistochemistry(IHC) and Western blotting(WB). Results TEM showed that hippocampus was significantly damaged by exposure, and exhibited recovery 1 week after exposure. The TUNEL data showed that neuronal apoptosis after exposure was significantly higher than in the control rats at 24 h and 48 h, and the apoptotic cells decreased one week after exposure. IHC and WB showed HSP70 expression was significantly higher in the exposed rats, peaked at 24 h. Conclusion Exposure to 140 d B(8 Hz) infrasound for 2 h per day for 3 days appeared to induce damage to the hippocampus of rats, based on changes in ultrastructure and increased cell apoptosis. However, recovery from the damage occurred overtime. HSP70 expression also increased after the exposure and decreased by 48 h.
文摘BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: D450 values of telomerase activity were 0.446 +/- 0.2700 in pancreatic cancer and 0.041 +/- 0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.
基金supported by FIS/IMSS project No.FIS/IMSS/PROT/G13/1216COFAA+1 种基金SIP-IPNby DGAPA-UNAM IN203616
文摘Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.
基金supported by Hunan Provincial Traditional Medicine Administration Bureau,No.2010044
文摘Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovadectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.