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Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
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Mice , Animals , Transcriptome , Aging/metabolism , Cochlea , Stria Vascularis , PresbycusisABSTRACT
RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.
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This study was aimed to observe the effect of Bai-Zhu Huang-Qi (BZHQ) decoction ethyl acetate extract on NOD like receptor family,pyrin domain-containing 3 (NLRP3) inflammasome in macrophages.The U937 cells were pretreated with phorbol 12-myristate 13-acetate (PMA,10 ng· mL-1) for 48 hours to induce macrophages.Effects on cell viability by different doses of BZHQ decoction ethyl acetate extract (0,3.125,6.25,12.5,25,50,100 μg· mL-1) were observed to select the appropriate concentration.Contents of NLRP3 and caspase-1 in cells were detected by real-time PCR and western blot.The concentration of interleukin-1β (IL-1β) in cell supernatant was detected by enzyme linked immunosorbent assay (ELISA).The cell counting kit-8 (CCK-8) assay showed that when the drug concentration was lower than 25 μg· mL-1,there was no impact on cell viability;when the drug concentration was higher than 50 μg· mL-1,there was inhibition on cell viability (P ＜ 0.05).The concentration of 25 μg· mL-1 was used to conduct the following experiment.Compared to the blank group,the expression of NLRP3 and caspase-l in cells of the LPS group were significantly increased (P ＜ 0.01).The concentration of IL-1β in cell supernatant was also significantly increased (P ＜ 0.01).After treated with BZHQ decoction ethyl acetate extract,levels of NLRP3,caspase-1 and IL-1β were significantly decreased (P ＜ 0.05).It was concluded that BZHQ decoction ethyl acetate extract can inhibit the production of NLRP3 inflammasome in LPS-stimulated macrophages.
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Objective To observe expression level of serum vascular endothelial growth factor-C (VEGF-C),VEGF-C receptor-2 and VEGF-C receptor-3 in patients with acute leukemia (AL) and to explore its clinical significance.Methods Enzyme-linked immuno sorbent assay (ELISA) was used to detect the serum expression levels of VEGF-C,VEGFR-2,and VEGFR-3 of 51 patients diagnosed with acute leukemia,43 patients under medical treatment and 16 healthy blood donors.Results (1) Serum VEGF-C,VEGFR-2,and VEGFR-3 expression levels in AL patients were significantly higher than those in normal control group.(2) Serum VEGF-C and VEGFR-2 expression levels in complete remission (CR) group significantly declined after treatment.Serum VEGF-C and VEGFR-2 expression levels in non-complete remission (NR) group slightly declined after treatment but no significant difference was found (P＞0.05).(3) No significant difference was found in serum VEGFR-3 expression levels both in CR group and NR group after treatment (P＞0.05).(4) Serum VEGF-C,VEGFR-2,and VEGFR-3 expression levels in NR group were significantly higher than those in CR group before treatment (P＜0.08).Conclusions Observing serum expression level of VEGF-C,VEGFR-2,and VEGFR-3 of AL patients may be helpful in monitoring curative effects and prognosis of acute leukemia.
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Objective Vascular endothelial growth factor( VEGF) is the key to regulat vascularization, and plays an important role in the development of acute myeloid leukemia. With the understanding of anti?tumor angiopoiesis, researchers take VEGF and its receptors as targets, continuously exploring the new drug. We summarized the biological characteristics of VEGF, vascular?targeted therapy and the clinical application of drugs.
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Objective To evaluate the effect of managed health education on psychological and nutritional status of patients with HBV-related cirrhosis and ascites.Methods One hundred and twenty one patents with decompensated HBV-related cirrhosis were enrolled for health education and randomly divided into two groups:61 patients received managed health education (trial group) and 60 received conventional health education (control group).In control group patients were informed with their condition and diet note by medical orders.In control group the hepatologists evaluated the baseline condition,nutritional status and quality of life,set up personal files of patients and followed up with communication and counselling periodically from June 2010 to August 2012.The psychological conditions were assessed with self-rating anxiety scale (SAS) and self-rating depression scale (SDS) ; nutritional status was assessed with triceps skinfold thickness (TSF) and mid-arm muscle circumference (MAMC) and the quality of life was assessed with MOS 36-item shoort from healthy survey (SF-36).Results Before health education,there was no statistical difference in the scores of SAS,SDS,TSF,SF-36 and blood Hb,albumin (Alb) levels between two groups.After health education,scores of SAS and SDS were decreased in both groups (P ＜ 0.0l),however,which in trial group were lower than those in control group (39.9 ±8.8 vs.49.0 ±9.4 and 40.6 ± 8.8 vs.51.9 ± 10.1 respectively,both P ＜0.01).The TSF scores and blood Hb and Alb levels in trial group were higher than those in control group (P ＜ 0.05).The accunulated scores of 8 dimensions in SF-36 forms in trial group were significantly higher than those in control group (P ＜ 0.01).Conclusion The managed health education model can better release psychological pressures,decrease mental disorders,elevate nutrition status,promote health and improve quality of life than conventional health education for patients with HBV-related cirrhosis and ascites.
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A questionnaire and telephone survey was conducted on 246 patients with chronic liver diseases in the Outpatient Clinic from August 2010 to May 2011.The distribution of diseases and the causes of losing follow-up were analyzed. Most subjects in this survey (182/246,74.0％ ) were patients with chronic viral hepatitis( HBV or HCV)and cirrhosis; and their follow-up status was better than others (X2 =12.382,P ＜ 0.05). There were no differences in gender( X2 =10.137,P ＞ 0.05),but significant differences in age ( X2 =31.783,P ＜ 0.05 ) and educational levels ( X2 =32.803,P ＜ 0.05 ) between patients with chronic viral hepatitis and cirrhosis and patients with other liver diseases.The main causes of losing follow-up were neglect of disease by patients (38.3％) and lack of good communication between doctors and patients ( 18.3％ ).It is important to reinforce the understanding and awareness of chronic liver diseases for patients.
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Objective To provide scientific evidence for nutrition therapy and health education for patients with type 2 diabetes mellitus (T2DM).Methods Based on body mass index (BMI),75 newly admitted T2DM patients were assigned to the normal body-weight group and the over-weight group.Three days before admission,their dietary status was investigated.The average energy intake was compared with the average standard supply.The energy from protein,fat or carbohydrate and the intake of fiber were compared with the recommendations from the American Diabetes Association (ADA).The intake of other nutrient was compared with the recommended nutrient intakes (RNI) or adequate intakes (AI).Results Compared with the standard supply,the average energy intake of the normal body-weight group was significantly decreased (t =2.61,P ＜ 0.05 ),however the average energy intake of the overweight group was significantly increased (t =3.91,P＜0.05).The percentage of energy from protein of the two groups was significantly higher than target levels ( t values were 13.23,21.13 respectively; all P ＜ 0.05 ) ; the percentage of energy from protein of the two groups was significantly higher than target levels (t values were 5.36,10.66 respectively ; all P ＜ 0.05 ) ; however,the percentage of energy from carbohydrate was lower in both groups ( t values were 6.94,15.76 respectively; all P ＜ 0.05 ) ; the average intake of fiber were also lower in both groups (t values were 26.54,40.80 respectively ; all P ＜ 0.05 ).ConclusionThe participants showed insufficient knowledge on healthy diet.Health education could play a role in balanced diet and energy intake.
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The change of Dietary pattern matched to a change in diseases spectrum of Chinese people in recent years. For improving the function of clinical nutrition branch in hospitals, in accordance with the change in the spectrum and patients' characters, we need to adjust the clinical nutrition treatments individually, to enhance the health education and consultation, to set new dietary pattern for people rationally, and to carry out the scientific research in the field of the relation between concerned chemical elements of organical foods and human health status in general, in order to reach the advanced hospital standards.
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Objective: To observe the effects of Radix Glycyrrhizae polysaccharide on regulatory T cells (Treg) in spleen and lymphocyte transformation ratio in tumor-bearing mice so as to explore the mechanisms of its immunoregulatory function. Methods: Fifty BALB/c mice were randomly divided into normal group, untreated group, cyclophosphamide group, Radix Glycyrrhizae polysaccharide group and Radix Glycyrrhizae polysaccharide plus cyclophosphamide group. Except normal group, mice were subcutaneously implanted H22 tumor cells in the right axillary region. After 24 h, mice in normal and untreated group were subcutaneously injected with physiological saline, while mice in the cyclophosphamide group were intraperitoneally injected with cyclophosphamide and mice in Radix Glycyrrhizae polysaccharide group were subcutaneously injected with polysaccharide. Fourteen days later, Treg cells of spleen were detected by flow cytometry and lymphocyte transformation ratio was detected by methyl thiazolyl tetrazolium method. Results: The proportion of Treg cells was significantly higher in the untreated group than in the normal group, and was lower in the Radix Glycyrrhizae polysaccharide group than in the untreated group (P
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@#ObjectiveTo establish a new method for preparing synaptosomes.MethodsDensity gradient centrifugation method was used to isolate synaptosomes of mouse, checking by transmission electron microscopy.ResultsSynaptosomes prepared by this method had intact morphological characteristics, surrounding with a continuous oval-shaped membrane structure, moreover, mitochondrion and lots of synaptic vesicle in them.ConclusionThis method is applicable to establish a rapid, convenient and useful method for preparing synaptosomes.
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@#ObjectiveTo explore the effects of high fat diet and caloric restriction on brain aging as well as the activity of Acetylcholinesterase(AChE) and afford scientific evidence to rational diet and prevent brain aging.MethodsSixty male ICR mice were randomly divided into 6 groups: the D-galactose-induced brain aging, brain aging plus high fat diet, brain aging plus caloric restriction, high fat diet only, caloric restriction only and normal control groups. Mice were given 100 mg/kg·d subcutaneous injection of D-galactose to prepare brain aging model for 9 weeks. Morris water maze (MWM) test was employed to determine their spatial learning and memory ability. Acetylcholinesterase (AChE) activity in brain was determined by hydroxylaminecolorimetric assay.ResultsIn Morris water maze test, brain aging mice showed a significant longer escape latency than the normal control mice (P<0.05). There was no statistical difference in escape latency between brain aging mice plus high fat diet and brain aging mice groups (P>0.05), and between the control and high fat diet groups (P>0.05). Brain aging mice plus caloric restriction exhibited a significant shorter escape latency than brain aging mice (P<0.05), but no difference was found when compared with normal control mice (P>0.05). There were no statistical difference in escape latency between the controls and caloric restriction group (P>0.05). The AChE activity in brain aging, brain aging plus high fat diet and brain aging plus caloric restriction group were higher than those in control and caloric restriction group (P<0.05). There were no statistical difference in AChE activity between the controls and caloric restriction group (P>0.05). Brain aging plus high fat diet were higher than brain aging and other non model control groups.ConclusionHigh fat diet can raise the activity of AChE effectively, but can not influence the capacity of learning and memory in mice. Caloric restriction can improve the capacity of learning and memory in mice, but has no significant influence on the activity of AChE in brain.
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@#Objective To observe effects for exercise and diet on learning and memory ability in mice with encephalon aging induced by D-galactose(D-gal).Methods The model of mice with encephalon aging was made by D-gal.The learning and memory ability of mice was determined by Morris water maze.Results There was significant difference between high fat feed encephalon aging group and restrict food on normal feed encephalon aging group,normal feed and exercise encephalon aging group,high fat feed and exercise encephalon aging group,high fat feed normal group,normal feed and exercise group,normal feed group(all P<0.05).In spatial probe test,there was significant difference between restrict food on normal feed encephalon aging group and normal feed encephalon aging group(all P<0.05).Conclusion Exercise and restrict food can improve the learning and memory function in the mice;feed with high fat can promote encephalon aging.
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Objective Establishment and characterization of healthy donor's ??T cell clones.Methods ??T cells were cloned by limiting dilution after positive sorting with 60Co irradiated allogeneic PBMC as feeder cells.Flow cytometry analysis and molecular biology technique were then used to identify ??T cell clones.MTT assay was used to verify their proliferation after incubated with epitope peptides recognized by ??T cells.Results A ??T cell clone had been established.The subtype of this clone was V ?9 V ?2 without expression of CD4 and CD8.Further studies indicated that epitope peptide EP6 could not only specifically bind to ??T cell clone but also trigger the proliferation of ??T cell clone.Conclusion A healthy donor's ??T cell clone was successfully established,which laid a solid foundation for further study on ??T cells.
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Objective To construct a cDNA library from human nasopharyngeal carcinoma cell HNE 2.Methods The total RNA was separated from human NPC(nasopharyngeal carcinoma)cell HNE 2 and the mRNA was isolated from the total RNA by MagneSphere technique,then the first-strand cDNA was synthesized with oligo(dT) primer containing sfiI site while the double-strand cDNA was amplified through LD-PCR(Long-distance PCR) by SMART technique.The double-strand cDNA was digested by sfiI(IA &IB)restriction enzyme before cDNA size fractionation ,the double-strand cDNA fractionated was ligated into the ?TripIEx2 vector and then was packaged in vitro.Results The unamplified human NPC cell HNE 2 cDNA library consists of 0 78?10 6 independent clones,and the percentage of recombinant clones was more than 96%.The titer of the amplified cDNA library was 1 02?10 9 pfu/ml and the average insert of the recombinants was 1 2kb.Conclusions The quality of the constructed human NPC cell HNE 2 cDNA library is excellent and helpful to screen NPC specific-antigen.