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Article: Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Rescue Testicular Aging.

Luo, Peng / Chen, Xuren / Gao, Feng / Xiang, Andy Peng / Deng, Chunhua / Xia, Kai / Gao, Yong

2024 Volume 12, Issue 1

Abstract: Background: Testicular aging is associated with diminished fertility and certain age-related ailments, and effective therapeutic interventions remain elusive. Here, we probed the therapeutic efficacy of exosomes derived from human umbilical cord ... ...

Abstract	Background: Testicular aging is associated with diminished fertility and certain age-related ailments, and effective therapeutic interventions remain elusive. Here, we probed the therapeutic efficacy of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exos) in counteracting testicular aging. Methods: We employed a model of 22-month-old mice and administered intratesticular injections of hUMSC-Exos. Comprehensive analyses encompassing immunohistological, transcriptomic, and physiological assessments were conducted to evaluate the effects on testicular aging. Concurrently, we monitored alterations in macrophage polarization and the oxidative stress landscape within the testes. Finally, we performed bioinformatic analysis for miRNAs in hUMSC-Exos. Results: Our data reveal that hUMSC-Exos administration leads to a marked reduction in aging-associated markers and cellular apoptosis while promoting cellular proliferation in aged testis. Importantly, hUMSC-Exos facilitated the restoration of spermatogenesis and elevated testosterone synthesis in aged mice. Furthermore, hUMSC-Exos could attenuate inflammation by driving the phenotypic shift of macrophages from M1 to M2 and suppress oxidative stress by reduced ROS production. Mechanistically, these efficacies against testicular aging may be mediated by hUMSC-Exos miRNAs. Conclusions: Our findings suggest that hUMSC-Exos therapy presents a viable strategy to ameliorate testicular aging, underscoring its potential therapeutic significance in managing testicular aging.
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12010098
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nestin

Huang, Jing / Deng, Ronghai / Li, Weiqiang / Jiang, Meihua / Xiang, Andy Peng / Zhang, Xiaoran

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are ... ...

Abstract	Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are still inconsistent owing to their heterogeneity. Spleen stromal cells have evolved to regulate the immune response at many levels as they are bathed in a complex inflammatory milieu during infection. Therefore, it is unknown whether they have stronger immunomodulatory effects than their counterparts derived from other tissues. Here, using a transgenic mouse model expressing GFP driven by the Nestin (
MeSH term(s)	Animals ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Cytokines ; Immunity ; Mice ; Mice, Transgenic ; Nestin/genetics ; Spleen ; Stromal Cells
Chemical Substances	Cytokines ; Nestin
Language	English
Publishing date	2022-10-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231911819
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Article ; Online: The U1 antisense morpholino oligonucleotide (AMO) disrupts U1 snRNP structure to promote intronic PCPA modification of pre-mRNAs.

Feng, Qiumin / Lin, Zejin / Deng, Yanhui / Ran, Yi / Yu, Rui / Xiang, Andy Peng / Ye, Congting / Yao, Chengguo

The Journal of biological chemistry

2023 Volume 299, Issue 7, Page(s) 104854

Abstract: Functional depletion of the U1 small nuclear ribonucleoprotein (snRNP) with a 25 nt U1 AMO (antisense morpholino oligonucleotide) may lead to intronic premature cleavage and polyadenylation of thousands of genes, a phenomenon known as U1 snRNP ... ...

Abstract	Functional depletion of the U1 small nuclear ribonucleoprotein (snRNP) with a 25 nt U1 AMO (antisense morpholino oligonucleotide) may lead to intronic premature cleavage and polyadenylation of thousands of genes, a phenomenon known as U1 snRNP telescripting; however, the underlying mechanism remains elusive. In this study, we demonstrated that U1 AMO could disrupt U1 snRNP structure both in vitro and in vivo, thereby affecting the U1 snRNP-RNAP polymerase II interaction. By performing chromatin immunoprecipitation sequencing for phosphorylation of Ser2 and Ser5 of the C-terminal domain of RPB1, the largest subunit of RNAP polymerase II, we showed that transcription elongation was disturbed upon U1 AMO treatment, with a particular high phosphorylation of Ser2 signal at intronic cryptic polyadenylation sites (PASs). In addition, we showed that core 3'processing factors CPSF/CstF are involved in the processing of intronic cryptic PAS. Their recruitment accumulated toward cryptic PASs upon U1 AMO treatment, as indicated by chromatin immunoprecipitation sequencing and individual-nucleotide resolution CrossLinking and ImmunoPrecipitation sequencing analysis. Conclusively, our data suggest that disruption of U1 snRNP structure mediated by U1 AMO provides a key for understanding the U1 telescripting mechanism.
MeSH term(s)	Morpholinos/metabolism ; Oligonucleotides, Antisense/metabolism ; Oligonucleotides, Antisense/pharmacology ; Polyadenylation ; Ribonucleoprotein, U1 Small Nuclear/genetics ; Ribonucleoprotein, U1 Small Nuclear/metabolism ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA Precursors/metabolism ; Humans ; HeLa Cells ; Gene Knockdown Techniques ; Cleavage And Polyadenylation Specificity Factor ; Cleavage Stimulation Factor/metabolism ; Transcription, Genetic/drug effects
Chemical Substances	Morpholinos ; Oligonucleotides, Antisense ; Ribonucleoprotein, U1 Small Nuclear ; RNA Polymerase II (EC 2.7.7.-) ; RNA Precursors ; Cleavage And Polyadenylation Specificity Factor ; CSTF3 protein, human ; Cleavage Stimulation Factor
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.104854
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Article ; Online: CFIm25 regulates human stem cell function independently of its role in mRNA alternative polyadenylation

Ran, Yi / Huang, Shanshan / Shi, Junjie / Feng, Qiumin / Deng, Yanhui / Xiang, Andy Peng / Yao, Chengguo

RNA Biology. 2022 Dec. 31, v. 19, no. 1 p.686-702

2022

Abstract: It has recently been shown that CFIm25, a canonical mRNA 3’ processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene ...

Abstract	It has recently been shown that CFIm25, a canonical mRNA 3’ processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene editing approach in human embryonic stem cells (hESCs) for CFIm25, and obtained three gene knockdown/mutant cell lines. CFIm25 gene editing resulted in higher proliferation rate and impaired differentiation potential for hESCs, with these effects likely to be directly regulated by the target genes, including the pluripotency factor rex1. Mechanistically, we unexpected found that perturbation in CFIm25 gene expression did not significantly affect cellular mRNA 3’ processing efficiency and APA profile. Rather, we provided evidences that CFIm25 may impact RNA polymerase II (RNAPII) occupancy at the body of transcribed genes, and promote the expression level of a group of transcripts associated with cellular proliferation and/or differentiation. Taken together, these results reveal novel mechanisms underlying CFIm25ʹs modulation in determination of cell fate, and provide evidence that the process of mammalian gene transcription may be regulated by an mRNA 3’ processing factor.
Keywords	CRISPR-Cas systems ; DNA-directed RNA polymerase ; RNA ; cell proliferation ; gene expression ; gene targeting ; genes ; humans ; mutants ; stem cells ; transcription (genetics) ; CFIm25 ; hESC pluripotency ; mRNA alternative polyadenylation ; gene transcription ; rex1
Language	English
Dates of publication	2022-1231
Size	p. 686-702.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2159587-2
ISSN	1555-8584
ISSN	1555-8584
DOI	10.1080/15476286.2022.2071025
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Article ; Online: The adipose-neural axis is involved in epicardial adipose tissue-related cardiac arrhythmias.

Fan, Yubao / Huang, Shanshan / Li, Suhua / Wu, Bingyuan / Zhao, Qi / Huang, Li / Zheng, Zhenda / Xie, Xujing / Liu, Jia / Huang, Weijun / Sun, Jiaqi / Zhu, Xiulong / Zhu, Jieming / Xiang, Andy Peng / Li, Weiqiang

Cell reports. Medicine

2024 Volume 5, Issue 5, Page(s) 101559

Abstract: Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an ... ...

Abstract	Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na
MeSH term(s)	Humans ; Animals ; Pericardium/metabolism ; Pericardium/pathology ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/pathology ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Neuropeptide Y/metabolism ; Leptin/metabolism ; Adipocytes/metabolism ; Male ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Neurons/metabolism ; Neurons/pathology ; Sodium-Calcium Exchanger/metabolism ; Female ; Receptors, Neuropeptide Y/metabolism ; Middle Aged ; Atrial Fibrillation/metabolism ; Atrial Fibrillation/physiopathology ; Atrial Fibrillation/pathology ; Sympathetic Nervous System/metabolism ; Mice ; Epicardial Adipose Tissue
Chemical Substances	Neuropeptide Y ; Leptin ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; Sodium-Calcium Exchanger ; Receptors, Neuropeptide Y
Language	English
Publishing date	2024-05-13
Publishing country	United States
Document type	Journal Article
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2024.101559
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Article ; Online: CD8+CD28- T cells: not only age-related cells but a subset of regulatory T cells.

Chen, Xiaoyong / Liu, Qiuli / Xiang, Andy Peng

Cellular & molecular immunology

2018 Volume 15, Issue 8, Page(s) 734–736

MeSH term(s)	Aged ; Aged, 80 and over ; Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Apoptosis ; Autoimmune Diseases/immunology ; Biomarkers ; CD28 Antigens/physiology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell- and Tissue-Based Therapy ; Cellular Senescence/immunology ; Coculture Techniques ; Graft vs Host Disease/therapy ; Humans ; Immunomodulation ; Infant, Newborn ; Inflammation/therapy ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/metabolism ; Mice ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tumor Microenvironment/immunology
Chemical Substances	Biomarkers ; CD28 Antigens ; TMIGD2 protein, human
Language	English
Publishing date	2018-01-29
Publishing country	China
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/cmi.2017.153
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Article: A potential mechanism underlying U1 snRNP inhibition of the cleavage step of mRNA 3’ processing

Deng, Yanhui / Shi, Junjie / Ran, Yi / Xiang, Andy Peng / Yao, Chengguo

Biochemical and biophysical research communications. 2020 Sept. 10, v. 530, no. 1

2020

Abstract: It is well established that U1 snRNP inhibits the cleavage of cryptic polyadenylation site (PAS) within introns, thereby facilitating full-length mRNA transcription for numerous genes in vertebrate cells, yet the underlying mechanism remains poorly ... ...

Abstract	It is well established that U1 snRNP inhibits the cleavage of cryptic polyadenylation site (PAS) within introns, thereby facilitating full-length mRNA transcription for numerous genes in vertebrate cells, yet the underlying mechanism remains poorly understood. Here, by using a model PAS of wdr26 mRNA, we show that U1 snRNP predominantly interferes with the association of PAS with a core 3′ processing factor CstF64, which can promote the cleavage step of mRNA 3′ processing. Furthermore, we provide evidence that U1A, a component of U1 snRNP, might directly interfere with CstF64 binding on PAS through its RNA binding capacity. Consistently, U1A could potentially associate with U1-suppressed intronic PASs at the transcriptome level in human cells, showing a binding peak ∼50 nt downstream of the cleavage site, as revealed by U1A iCLIP-seq (individual-nucleotide resolution UV crosslinking and immunoprecipitation coupled with RNA sequencing) analysis. Together, our data suggest a molecular mechanism underlying U1 snRNP inhibition of the cleavage step of mRNA 3′ processing. More generally, we argue that U1 snRNP might inhibit the usage of cryptic PASs through disturbing the recruitment of core 3’ processing factors.
Keywords	crosslinking ; humans ; introns ; precipitin tests ; research ; transcriptome
Language	English
Dates of publication	2020-0910
Size	p. 196-202.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.06.092
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Accurate Machine Learning Model to Diagnose Chronic Autoimmune Diseases Utilizing Information From B Cells and Monocytes.

Ma, Yuanchen / Chen, Jieying / Wang, Tao / Zhang, Liting / Xu, Xinhao / Qiu, Yuxuan / Xiang, Andy Peng / Huang, Weijun

Frontiers in immunology

2022 Volume 13, Page(s) 870531

Abstract: Heterogeneity and limited comprehension of chronic autoimmune disease pathophysiology cause accurate diagnosis a challenging process. With the increasing resources of single-cell sequencing data, a reasonable way could be found to address this issue. In ... ...

Abstract	Heterogeneity and limited comprehension of chronic autoimmune disease pathophysiology cause accurate diagnosis a challenging process. With the increasing resources of single-cell sequencing data, a reasonable way could be found to address this issue. In our study, with the use of large-scale public single-cell RNA sequencing (scRNA-seq) data, analysis of dataset integration (3.1 × 10
MeSH term(s)	Arthritis, Rheumatoid ; Humans ; Leukocytes, Mononuclear ; Lupus Erythematosus, Systemic/diagnosis ; Machine Learning ; Monocytes ; Single-Cell Analysis
Language	English
Publishing date	2022-04-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.870531
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Article: Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability.

Wei, Yili / Wang, Bin / Jia, Lei / Huang, Weijun / Xiang, Andy Peng / Fang, Cong / Liang, Xiaoyan / Li, Weiqiang

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 767536

Abstract: Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially ... ...

Abstract	Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.
Language	English
Publishing date	2022-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.767536
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Article ; Online: AAV-mediated gene therapy restores natural fertility and improves physical function in the Lhcgr-deficient mouse model of Leydig cell failure.

Zhang, Suyuan / Yang, Bin / Shen, Xiaoting / Chen, Hong / Wang, Fulin / Tan, Zhipeng / Ou, Wangsheng / Yang, Cuifeng / Liu, Congyuan / Peng, Hao / Luo, Peng / Peng, Limei / Lei, Zhenmin / Yan, Sunxing / Wang, Tao / Ke, Qiong / Deng, Chunhua / Xiang, Andy Peng / Xia, Kai

Cell proliferation

2024 , Page(s) e13680

Abstract: Leydig cell failure (LCF) caused by gene mutations leads to testosterone deficiency, infertility and reduced physical function. Adeno-associated virus serotype 8 (AAV8)-mediated gene therapy shows potential in treating LCF in the Lhcgr-deficient ( ... ...

Abstract	Leydig cell failure (LCF) caused by gene mutations leads to testosterone deficiency, infertility and reduced physical function. Adeno-associated virus serotype 8 (AAV8)-mediated gene therapy shows potential in treating LCF in the Lhcgr-deficient (Lhcgr
Language	English
Publishing date	2024-05-30
Publishing country	England
Document type	Journal Article
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0008-8730 ; 0960-7722
ISSN (online)	1365-2184
ISSN	0008-8730 ; 0960-7722
DOI	10.1111/cpr.13680
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