Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hosp...Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer （PCa） cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme.linked immunosorbent assay （ELISA） in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio （OR）： 0.66, 95% confidence interval （CI） =0.48-0.92] and increased plasma adiponectin levels （P= 0.036 and 0,043）, with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa （P=6.7 × 10-3）. ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.展开更多
PCR-DGGE approach was used to analyze bacterial diversity in the bottomsection of seven arctic sea ice samples colleted from the Canada Basin.Thirty-two 16S rDNAsequences were obtained from prominent DGGE bands.The cl...PCR-DGGE approach was used to analyze bacterial diversity in the bottomsection of seven arctic sea ice samples colleted from the Canada Basin.Thirty-two 16S rDNAsequences were obtained from prominent DGGE bands.The closest relatives of these sequences arefound to be those of cultivated or uncultured bacteria from antarctic or arctic sea ice.Phylogenetic analysis clustered these sequences or phylotypes withinα-proteobacteria,γ-proteobacteria and CFB(cytophaga-flexibacter-bacteroides)group.Sequences belonging toγ-proteobacteria were dominant and members of the CFB group were highly abundant.It was suggestedthat the CFB group was the representative of the bottom section of sea ice samples.展开更多
Prostate cancer （PCa） is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is...Prostate cancer （PCa） is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and Iow-penetrance PCa risk-associated single-nucleotide polymorphisms （SNPs） from genetic association studies in PCa cases and controls, especially those from genome-wide association studies （GWASs）. A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations.展开更多
The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease....The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.展开更多
BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the...BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.展开更多
In China,rare diseases are defined as having a birth incidence of less than 1/10000,or a prevalence of less than 1/10000 or less than 140000 patients.Over 7000 rare diseases affect more than 20 million people in China...In China,rare diseases are defined as having a birth incidence of less than 1/10000,or a prevalence of less than 1/10000 or less than 140000 patients.Over 7000 rare diseases affect more than 20 million people in China.Many conditions are misdiagnosed or undiagnosed and most have no treatment,resulting in a huge burden on patients,their families,and the national economy.At the 297th Shuangqing Forum of the National Natural Science Foundation of China,we highlighted the challenges and potential solutions to achieve precision medicine for undiagnosed and rare diseases.展开更多
Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below ...Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below 30%, especially among patients with PSA levels at 4-10 ng ml-1. In the past several years, additional biomarkers, such as Prostate Health Index, PCA3 and genetic risk score （GRS） derived from multiple PCa risk-associated single nucleotide polymorphisms （SNPs） have been shown to provide added value to PSA in discriminating prostate biopsy outcomes. However,展开更多
Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hund...Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.展开更多
Bacterial diversity in sea ice brine samples which collected from four stations located at the Canada Basin, Arctic Ocean was analyzed by PCR-DGGE. Twenty-three 16S rDNA sequences of bacteria obtained from DGGE bands ...Bacterial diversity in sea ice brine samples which collected from four stations located at the Canada Basin, Arctic Ocean was analyzed by PCR-DGGE. Twenty-three 16S rDNA sequences of bacteria obtained from DGGE bands were cloned and sequenced. Phylogenetic analysis clustered these sequences within γ-proteobacteria, Cytophaga-Flexlbacter-Bacteroides （CFB） group, Firmicutes and Actinobacteria. The phylotype of Pseudoalteromonas in the γ-proteobacteria was predominant and members of the CFB group and γ-proteobacteria were highly abundant in studied sea ice brine samples.展开更多
Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research h...Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.展开更多
Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)cons...Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.展开更多
In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and p...In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability.展开更多
References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary...References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary Data 1 Elsevier Science Bulletin Volume 70,Issue 5,15 March 2025,Pages 638-642 Science Bulletin Short Communication DNA methylation and genetic regulation in natural populations of East Asian and mixed Eurasian ancestry Author links open overlay panel Shuangshuang Cheng a,Zhilin Ning b,Yan Lu a e,Yuhan Du a,Xiaonan Yang c,Minghui Li c,Dilinuer Maimaitiyiming d,Shuhua Xu a f a State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Center for Evolutionary Biology,School of Life Sciences,Department of Liver Surgery and Transplantation Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China b Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China c Sinotech Genomics Co.,Ltd.,Shanghai 200120,China d The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China e Ministry of Education Key Laboratory of Contemporary Anthropology,Fudan University,Shanghai 200438,China f School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China Received 27 March 2024,Revised 16 July 2024,Accepted 30 September 2024,Available online 15 October 2024,Version of Record 10 March 2025.What do these dates mean?Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.scib.2024.10.006 Get rights and content Under a Creative Commons license Open access Graphical abstract Download:Download high-res image(109KB)Download:Download full-size image Previous article Next article As an important epigenetic marker,DNA methylation(DNAm)is a stably inherited epigenetic modification that plays an important role in mammalian epigenetics.DNAm is influenced by genetic and environmental factors[1],and has different functions in different genomic contexts.It has been suggested that a large proportion of DNAm differences are associated with allele frequency divergence[2].In addition,significant differences in cis-DNA methylation quantitative trait loci were found in three Southeast Asian populations[3].The epigenetic structure of DNAm in several populations in China has also been reported recently[4].Some genome-wide studies have identified ancestral origins and population relationships;for example,the Uyghurs have approximately a half-Eastern and half-Western genetic composition[5],[6].Notably,a recent study explored the genetic basis of highly differentiated gene expression with east–west origins in Uyghurs[7].However,our understanding of DNAm profiles and their genetic basis remains limited,particularly in 1:1 mixed-descent populations.In this study,we constructed a DNAm map with data from 92 Uyghurs(XJU)and 33 Han Chinese(HAN)individuals.The procedures followed the ethical standards of the Responsible Committee on Human Experimentation and were approved by the Biomedical Research Ethics Committee of Shanghai Institutes for Biological Sciences(ER-SIBS-261408)and the Helsinki Declaration of 1975(revised in 2000).Each individual was the offspring of a nonconsanguineous marriage of members of the same nationality within three generations.We identified the highly differentiated DNAm positions and regions between HAN and XJU.We then examined the correlation between the level of genetic differences and the level of DNAm differences.Finally,we studied the relationship between the genomic and epigenetic data at the global and local levels.展开更多
N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 h...N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response （UPR） pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo.展开更多
Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they...Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To furtherunderstand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventionsthat can be used in future exercise-related studies.Methods'. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treatingvarious diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity[Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters:one that limited publication dates to "in 10 years,^ and one that sorted the results as "best match^^. Then we grouped the commonly used exercisemethods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseasesand organ functions in 8 different systems.Results'. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exerciseinterventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascularsystem (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and thesystem related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntarywheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, mostof them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless ofthe exercise method used, although some diseases showed the best remission effects when a specific method was used.Conclusion-. Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exerciseinterventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention com・pliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exerciseinterventions in humans.展开更多
AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by i...AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.展开更多
Asthma is a common chronic inflammatory disorder that is more prevalent in children than in adults.China has seen an increasing prevalence of childhood asthma in recentdecades[1].Earlier studies have shown that air pa...Asthma is a common chronic inflammatory disorder that is more prevalent in children than in adults.China has seen an increasing prevalence of childhood asthma in recentdecades[1].Earlier studies have shown that air particulate matter (PM),particularly fine particulate matter(PM2.5)[2],is an important factor triggering childhood asthma. Since nationalPM2.5data were nota vailabl euntil 2013,展开更多
MtDNA was successfully extracted from ten individual bones (femurs) in the tombs of ancient Jushi in Turfan basin, dated back to the year about 3 000-2 500 years ago. By means of four overlapping primers, we got nucl...MtDNA was successfully extracted from ten individual bones (femurs) in the tombs of ancient Jushi in Turfan basin, dated back to the year about 3 000-2 500 years ago. By means of four overlapping primers, we got nucleotide sequence of the 218bp length. Ancient mtDNA was analyzed by the sequencing of hypervariable region Ⅰ of the mtDNA control region. The result shows that 9 haplotypes with 24 polymorphic sites were obtained. The phylogenetic analysis indicated that Mongolians and Altai are the population genetically closest to the Jushi groups and Jushi mtDNA pool being an admixture of eastern Asian and European lineages. So our preliminary data imply that an ancient mingling of Euro-Asian population had existed in Turfan basin prior to the early Iron Age.展开更多
AIM: To study the pathogenetic processes and the role of gene expression by microarray analyses in expediting our understanding of the molecular pathophysiology of pancreatic adenocarcinoma, and to identify the novel ...AIM: To study the pathogenetic processes and the role of gene expression by microarray analyses in expediting our understanding of the molecular pathophysiology of pancreatic adenocarcinoma, and to identify the novel cancer-associated genes.METHODS: Nine histologically defined pancreatic head adenocarcinoma specimens associated with clinical data were studied. Total RNA and mRNA were isolated and labeled by reverse transcription reaction with Cy5 and Cy3 for cDNA probe. The cDNA microarrays that represent a set of 4 096 human genes were hybridized with labeled cDNA probe and screened for molecular profiling analyses.RESULTS: Using this methodology, 184 genes were screened out for differences in gene expression level after nine couples of hybridizations. Of the 184 genes,87 were upregulated and 97 downregulated, including 11 novel human genes. In pancreatic adenocarcinoma tissue, several invasion and metastasis related genes showed their high expression levels, suggesting that poor prognosis of pancreatic adenocarcinoma might have a solid molecular biological basis.CONCLUSION: The application of cDNA microarray technique for analysis of gene expression patterns is a powerful strategy to identify novel cancer-associated genes, and to rapidly explore their role in clinical pancreatic adenocarcinoma. Microarray profiles provide us new insights into the carcinogenesis and invasive process of pancreatic adenocarcinoma. Our results suggest that a highly organized and structured process of tumor invasion exists in the pancreas.展开更多
In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation...In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-βas the central cause of Alzheimer’s disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-βand their potential association in the pathological process of Alzheimer’s disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer’s disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Together,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer’s disease drugs.展开更多
文摘Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer （PCa） cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme.linked immunosorbent assay （ELISA） in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio （OR）： 0.66, 95% confidence interval （CI） =0.48-0.92] and increased plasma adiponectin levels （P= 0.036 and 0,043）, with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa （P=6.7 × 10-3）. ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.
基金supported by the National Basic Research Program of China under coutract No.2004CB719601the Science and Technology Basic Work Program of China under coutract No.2003DEB5J057+1 种基金the National Natural Science Foundation of China under contract No.40376001This work is also a part of the Project"Second Chinese National Arctic Research Expedition"or CHINARE-2003 supported by the Ministry of Finance of China and organized by the Chinese Arctic and Antarctic Administration(CAA).
文摘PCR-DGGE approach was used to analyze bacterial diversity in the bottomsection of seven arctic sea ice samples colleted from the Canada Basin.Thirty-two 16S rDNAsequences were obtained from prominent DGGE bands.The closest relatives of these sequences arefound to be those of cultivated or uncultured bacteria from antarctic or arctic sea ice.Phylogenetic analysis clustered these sequences or phylotypes withinα-proteobacteria,γ-proteobacteria and CFB(cytophaga-flexibacter-bacteroides)group.Sequences belonging toγ-proteobacteria were dominant and members of the CFB group were highly abundant.It was suggestedthat the CFB group was the representative of the bottom section of sea ice samples.
基金This work was partially funded by the National Key Basic Research Program Grant 973 （No.2012CB518301） to JX, the Key Project of the National Natural Science Foundation of China （No.81130047） to IX, intramural grants from Fudan University ＇Thousand Talents Program＇ and Huashan Hospital to JX and the National Institutes of Health （No.NCI CA129684） to IX.
文摘Prostate cancer （PCa） is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and Iow-penetrance PCa risk-associated single-nucleotide polymorphisms （SNPs） from genetic association studies in PCa cases and controls, especially those from genome-wide association studies （GWASs）. A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations.
基金This work was supported by grants from the National Natural Science Foundation of China （21375144 and 21105115） and the National Basic Research Program of China （2012CB934004）.
文摘The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.
文摘BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.
文摘In China,rare diseases are defined as having a birth incidence of less than 1/10000,or a prevalence of less than 1/10000 or less than 140000 patients.Over 7000 rare diseases affect more than 20 million people in China.Many conditions are misdiagnosed or undiagnosed and most have no treatment,resulting in a huge burden on patients,their families,and the national economy.At the 297th Shuangqing Forum of the National Natural Science Foundation of China,we highlighted the challenges and potential solutions to achieve precision medicine for undiagnosed and rare diseases.
基金I thank for the contributions of study populations, data analysis and discussion to this paper from Drs S Lilly Zheng and lielin Sun from Wake Forest School of Medicine Dr Henrik Gronberg from Karolinska Institutet of Sweden+2 种基金 Mr Haitao Chen from School of Life Science, Fudan University, China Dr Qiang Ding, Ms Fang Liu and Xiaoling Lin from Fudan Institute of Urology, Fudan University, China Drs Yinghao Sun, Shangchen Ren and Zhensheng Zhang from Changhai Hospital, China and Dr Donna P Ankerst from Technical University Munich, Germany. This work was partially funded by the National Key Basic Research Program Grant 973 （No. 2012CB518301）, the Key Project of the National Natural Science Foundation of China （No. 81130047）, intramural grants from Fudan University and Huashan Hospital and the National Institutes of Health （No. NCI CA 129684）.
文摘Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below 30%, especially among patients with PSA levels at 4-10 ng ml-1. In the past several years, additional biomarkers, such as Prostate Health Index, PCA3 and genetic risk score （GRS） derived from multiple PCa risk-associated single nucleotide polymorphisms （SNPs） have been shown to provide added value to PSA in discriminating prostate biopsy outcomes. However,
基金financial supports from the National Key R&D Program of China(Grant Nos.:2022YFC3400700,2022YFA0806400,and 2020YFE0201600)Shanghai Municipal Science and Technology Major Project(Grant No.:2017SHZDZX01)the National Natural Science Foundation of China(Grant No.:31821002).
文摘Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.
文摘Bacterial diversity in sea ice brine samples which collected from four stations located at the Canada Basin, Arctic Ocean was analyzed by PCR-DGGE. Twenty-three 16S rDNA sequences of bacteria obtained from DGGE bands were cloned and sequenced. Phylogenetic analysis clustered these sequences within γ-proteobacteria, Cytophaga-Flexlbacter-Bacteroides （CFB） group, Firmicutes and Actinobacteria. The phylotype of Pseudoalteromonas in the γ-proteobacteria was predominant and members of the CFB group and γ-proteobacteria were highly abundant in studied sea ice brine samples.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077,81961128025,and 82121002)the Research Projects from the Science and Technology Commission of Shanghai Municipality(Grant Nos.21JC1401200,20JC1418900,and 21JC1410100)to QG,the China National Postdoctoral Program for Innovative Talents(Grant No.BX20240090)the China Postdoctoral Science Foundation(Grant No.2024M750551)to MZ.
文摘Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.
基金supported by the National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82073267,82203399,82372689)+1 种基金Program for Outstanding Leading Talents in ShanghaiInnovative Research Team of High-level Local University in Shanghai。
文摘Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.
基金supported by the Innovation Program of the Shanghai Municipal Education Commission(2023ZKZD05)the Shanghai Oriental Talent(Rural Revitalization)Top Talent Project(T2023102).
文摘In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability.
基金National Key Research and Development Program of China(2023YFC2605400)National Natural Science Foundation of China(32030020,32288101,and 32470649)+2 种基金Shanghai Science and Technology Commission Program(23JS1410100)Office of Global Partnerships(Key Projects Development Fund)The computational work in this study was supported by the CFFF Computing Platform of Fudan University.The funders had no role in the study design,data collection,analysis,decision to publish,or preparation of the manuscript.
文摘References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary Data 1 Elsevier Science Bulletin Volume 70,Issue 5,15 March 2025,Pages 638-642 Science Bulletin Short Communication DNA methylation and genetic regulation in natural populations of East Asian and mixed Eurasian ancestry Author links open overlay panel Shuangshuang Cheng a,Zhilin Ning b,Yan Lu a e,Yuhan Du a,Xiaonan Yang c,Minghui Li c,Dilinuer Maimaitiyiming d,Shuhua Xu a f a State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Center for Evolutionary Biology,School of Life Sciences,Department of Liver Surgery and Transplantation Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China b Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China c Sinotech Genomics Co.,Ltd.,Shanghai 200120,China d The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China e Ministry of Education Key Laboratory of Contemporary Anthropology,Fudan University,Shanghai 200438,China f School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China Received 27 March 2024,Revised 16 July 2024,Accepted 30 September 2024,Available online 15 October 2024,Version of Record 10 March 2025.What do these dates mean?Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.scib.2024.10.006 Get rights and content Under a Creative Commons license Open access Graphical abstract Download:Download high-res image(109KB)Download:Download full-size image Previous article Next article As an important epigenetic marker,DNA methylation(DNAm)is a stably inherited epigenetic modification that plays an important role in mammalian epigenetics.DNAm is influenced by genetic and environmental factors[1],and has different functions in different genomic contexts.It has been suggested that a large proportion of DNAm differences are associated with allele frequency divergence[2].In addition,significant differences in cis-DNA methylation quantitative trait loci were found in three Southeast Asian populations[3].The epigenetic structure of DNAm in several populations in China has also been reported recently[4].Some genome-wide studies have identified ancestral origins and population relationships;for example,the Uyghurs have approximately a half-Eastern and half-Western genetic composition[5],[6].Notably,a recent study explored the genetic basis of highly differentiated gene expression with east–west origins in Uyghurs[7].However,our understanding of DNAm profiles and their genetic basis remains limited,particularly in 1:1 mixed-descent populations.In this study,we constructed a DNAm map with data from 92 Uyghurs(XJU)and 33 Han Chinese(HAN)individuals.The procedures followed the ethical standards of the Responsible Committee on Human Experimentation and were approved by the Biomedical Research Ethics Committee of Shanghai Institutes for Biological Sciences(ER-SIBS-261408)and the Helsinki Declaration of 1975(revised in 2000).Each individual was the offspring of a nonconsanguineous marriage of members of the same nationality within three generations.We identified the highly differentiated DNAm positions and regions between HAN and XJU.We then examined the correlation between the level of genetic differences and the level of DNAm differences.Finally,we studied the relationship between the genomic and epigenetic data at the global and local levels.
文摘N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response （UPR） pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo.
基金supported by the Major Research Plan of the National Natural Science Foundation of China (91749104)the Emergency Management Project of the National Natural Science Foundation of China (31842034)+3 种基金the Shanghai Pujiang Talent Project (18PJ1400700)the Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee (18140901300)the Open Research Fund of the National Key Laboratory of Genetic Engineering (SKLGE1803)the Open Research Fund of the State Key Laboratory of Pharmaceutical Biotechnology (KF-GN201701) to TML
文摘Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To furtherunderstand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventionsthat can be used in future exercise-related studies.Methods'. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treatingvarious diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity[Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters:one that limited publication dates to "in 10 years,^ and one that sorted the results as "best match^^. Then we grouped the commonly used exercisemethods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseasesand organ functions in 8 different systems.Results'. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exerciseinterventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascularsystem (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and thesystem related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntarywheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, mostof them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless ofthe exercise method used, although some diseases showed the best remission effects when a specific method was used.Conclusion-. Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exerciseinterventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention com・pliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exerciseinterventions in humans.
基金Supported by the National Natural Science Foundation of China, No. 30571759Social Development Foundation of Shanghai, No. 200253
文摘AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.
基金supported by the Development Foundation of Shanghai Meteorological and Health Key Laboratory [QXJK201606]the Investigation of Science&Technology Basic Resources Program of China [2017FY101206]the General Program Foundation of Hebei Meteorological Bureau [17KY10]
文摘Asthma is a common chronic inflammatory disorder that is more prevalent in children than in adults.China has seen an increasing prevalence of childhood asthma in recentdecades[1].Earlier studies have shown that air particulate matter (PM),particularly fine particulate matter(PM2.5)[2],is an important factor triggering childhood asthma. Since nationalPM2.5data were nota vailabl euntil 2013,
基金Supported by Fund for the Important Project of the Science and Technology DepartmentMinistry of Education
文摘MtDNA was successfully extracted from ten individual bones (femurs) in the tombs of ancient Jushi in Turfan basin, dated back to the year about 3 000-2 500 years ago. By means of four overlapping primers, we got nucleotide sequence of the 218bp length. Ancient mtDNA was analyzed by the sequencing of hypervariable region Ⅰ of the mtDNA control region. The result shows that 9 haplotypes with 24 polymorphic sites were obtained. The phylogenetic analysis indicated that Mongolians and Altai are the population genetically closest to the Jushi groups and Jushi mtDNA pool being an admixture of eastern Asian and European lineages. So our preliminary data imply that an ancient mingling of Euro-Asian population had existed in Turfan basin prior to the early Iron Age.
基金Supported by the National Natural Science Foundation of China,No. 30000160
文摘AIM: To study the pathogenetic processes and the role of gene expression by microarray analyses in expediting our understanding of the molecular pathophysiology of pancreatic adenocarcinoma, and to identify the novel cancer-associated genes.METHODS: Nine histologically defined pancreatic head adenocarcinoma specimens associated with clinical data were studied. Total RNA and mRNA were isolated and labeled by reverse transcription reaction with Cy5 and Cy3 for cDNA probe. The cDNA microarrays that represent a set of 4 096 human genes were hybridized with labeled cDNA probe and screened for molecular profiling analyses.RESULTS: Using this methodology, 184 genes were screened out for differences in gene expression level after nine couples of hybridizations. Of the 184 genes,87 were upregulated and 97 downregulated, including 11 novel human genes. In pancreatic adenocarcinoma tissue, several invasion and metastasis related genes showed their high expression levels, suggesting that poor prognosis of pancreatic adenocarcinoma might have a solid molecular biological basis.CONCLUSION: The application of cDNA microarray technique for analysis of gene expression patterns is a powerful strategy to identify novel cancer-associated genes, and to rapidly explore their role in clinical pancreatic adenocarcinoma. Microarray profiles provide us new insights into the carcinogenesis and invasive process of pancreatic adenocarcinoma. Our results suggest that a highly organized and structured process of tumor invasion exists in the pancreas.
基金supported by the National Key Research and Development Program of ChinaNos.2021YFC2 701800 and 2021YFC2 701805 (to QY)+2 种基金Open Research Fund of State Key Laboratory of Genetic EngineeringFudan UniversityNo.SKLGE-21 19 (to TXH and QY)
文摘In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-βas the central cause of Alzheimer’s disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-βand their potential association in the pathological process of Alzheimer’s disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer’s disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Together,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer’s disease drugs.
