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1.
EMBO J ; 39(7): e103255, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32128839

ABSTRACT

The Hippo-YAP signaling pathway plays an essential role in epithelial cells during intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here, we report a stroma-epithelium ISLR-YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis. Specifically, upon inflammation and in cancer, an oncogenic transcription factor ETS1 in stromal cells induces expression of a secreted protein ISLR that can inhibit Hippo signaling and activate YAP in epithelial cells. Deletion of Islr in stromal cells in mice markedly impaired intestinal regeneration and suppressed tumorigenesis in the colon. Moreover, the expression of stromal cell-specific ISLR and ETS1 significantly increased in inflamed mucosa of human IBD patients and in human colorectal adenocarcinoma, accounting for the epithelial YAP hyperactivation. Collectively, our findings provide new insights into the signaling crosstalk between stroma and epithelium during tissue regeneration and tumorigenesis.


Subject(s)
Colorectal Neoplasms/metabolism , Immunoglobulins/genetics , Immunoglobulins/metabolism , Inflammatory Bowel Diseases/metabolism , Proto-Oncogene Protein c-ets-1/metabolism , Animals , Colorectal Neoplasms/genetics , Disease Models, Animal , Gene Knockout Techniques , HCT116 Cells , HEK293 Cells , HT29 Cells , Hippo Signaling Pathway , Humans , Inflammatory Bowel Diseases/genetics , Intestinal Mucosa/metabolism , Male , Mice , Mutation , Promoter Regions, Genetic , Protein Serine-Threonine Kinases/metabolism , Signal Transduction
2.
FASEB J ; 37(8): e23084, 2023 08.
Article in English | MEDLINE | ID: mdl-37410073

ABSTRACT

Spermatogenesis is a highly organized process by which undifferentiated spermatogonia self-renew and differentiate into spermatocytes and spermatids. The entire developmental process from spermatogonia to sperm occurs within the seminiferous tubules. Spermatogenesis is supported by the close interaction of germ cells with Sertoli cells. In this study, testicular tissues were collected from Hu sheep at 8 timepoints after birth: 0, 30, 90, 180, 270, 360, 540, and 720 days. Immunofluorescence staining and histological analysis were used to explore the development of male germ cells and Sertoli cells in the Hu sheep testes at these timepoints. The changes in seminiferous tubule diameter and male germ cells in the Hu sheep testes at these different developmental stages were analyzed. Then, specific molecular markers were used to study the proliferation and differentiation of spermatogonia, the timepoint of spermatocyte appearance, and the maturation and proliferation of Sertoli cells in the seminiferous tubules. Finally, the formation of the blood-testes barrier was studied using antibodies against the main components of the blood-testes barrier, ß-catenin, and ZO-1. These findings not only increased the understanding of the development of the Hu sheep testes, but also laid a solid theoretical foundation for Hu sheep breeding.


Subject(s)
Sertoli Cells , Testis , Male , Animals , Sheep , Semen , Spermatogenesis , Spermatogonia
3.
Small ; 19(46): e2305326, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37501332

ABSTRACT

Composite solid electrolytes (CSEs) consisting of polyethylene oxide (PEO) matrix and active inorganic fillers have shown great potential for practical applications. However, mechanisms of how different active fillers enhance ion transport in CSEs still remain inconclusive. In this work, the component dependencies of ionic conductivity of PEO-based CSEs are investigated by comparing two widely investigated active fillers: NASICON-type (LATP) and garnet-type (LLZTO). In terms of ionic conductivity, the optimum ratios are strikingly different for LLZTO (10 wt%) and LATP (50 wt%). Through experimental and computational studies, it is demonstrated that the high affinity between LATP and PEO facilitates unhindered interfacial Li+ transfer so that LATP functions as a bulk-active filler to provide additional inorganic ion pathways. By contrast, Li+ transfer between LLZTO and PEO is found to be sluggish. Instead, LLZTO mainly improves ionic conductivity by dissociating lithium salt, making it a surface-active filler. Through categorizing active fillers based on their Li+ conductive mechanisms, this work provides new understanding and guidelines for componential design and optimization of solid composite electrolytes.

4.
Biol Reprod ; 108(6): 887-901, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37040346

ABSTRACT

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.


Subject(s)
Induced Pluripotent Stem Cells , Horses , Animals , Cellular Reprogramming , Equidae , Cells, Cultured , Cell Differentiation/genetics , Fibroblasts , Octamer Transcription Factor-3/genetics
5.
Altern Ther Health Med ; 29(4): 194-199, 2023 May.
Article in English | MEDLINE | ID: mdl-36947654

ABSTRACT

Context: Because the early symptoms of primary hepatocellular carcinoma (PHC) aren't significant, it's difficult to diagnose it by routine inspection clinically, and if the lesion's diameter is small, less than 2.0 cm, false negatives can occur in pathological examinations. Researchers need to actively search for more diagnostic methods. Objective: The study intended to detect and analyze the value of plasma Septin9 gene methylation for the diagnosis and therapeutic monitoring of PHC in older adults. Design: The research team performed a prospective controlled study. Setting: The study took place at the First Hospital of Qiqihar, an Affiliated Qiqihar Hospital at Southern Medical University in Qiqihar, China. Participants: Participants were 32 patients with PHC and 28 with cholangiocarcinoma (CCA) who had been admitted to the hospital between January 2021 and July 2022 and 40 healthy individuals. Groups: The research team divided participants into three groups: (1) patients with PHC, the PHC group; (2) patients with CCA, the CCA group; and (3) healthy individuals, the control group. Outcome Measures: The research team: (1) determined the positive expression rate of Septin9 gene methylation; (2) measured liver function indicators-alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), albumin (ALB); and (3) measured tumor markers-alpha-fetoprotein (AFP), carbohydrate antigen (CA) 199, CA125, and CA153. The team also: (1) established a binary logistic regression model based on levels of GGT and plasma Septin9 gene methylation to analyze risk factors and diagnosis accuracy, (2) created a receiver operating characteristic (ROC) curve to analyze diagnostic values; and (3) during followup, analyzed the negative conversion rate of Septin9 gene methylation in participants. Results: The positive expression rate of Septin9 methylation in the PHC group was significantly lower than that that of the CCA group and significantly higher than that of the control group (P < .05). The PHC group's ALT, AST, TBIL, DBIL, ALP, and GGT were significantly higher than those of the control group but significantly lower than those of the CCA group (all P < .05). PHC group's ALB was significantly lower than that of the control group (P < .05). The PHC group's AFP, CA199, and CA125 were significantly higher than those of the control group, and the PHC group's CA199 and CA125 were significantly lower than those in the CCA group (all P < .05). The positive expression of Septin9 gene methylation and the high expression of GGT were risk factors for PHC (OR>1, P < .05). The AUC of the Septin9 gene methylation, the GGT level, and the combined detection of both variables (all AUC > 0.70), suggests that the variables have a diagnostic value in the detection of PHC, with the combined detection having the highest value. The negative conversion rate after surgery of Septin9 gene methylation was 87.10%, for 27 out of 31 participants in the PHC and CCA groups (χ2 = 29.405, P < .001). Conclusion: Plasma Septin9 gene methylation is a sensitive molecular marker for the diagnosis and therapeutic monitoring of older adults with PHC, and combined with the serum GGT level, has a high diagnostic efficiency, which may reflect the treatment status of patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Aged , Humans , alpha-Fetoproteins , Bilirubin , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , gamma-Glutamyltransferase , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Methylation , Prospective Studies
6.
Small ; 18(23): e2200548, 2022 06.
Article in English | MEDLINE | ID: mdl-35460191

ABSTRACT

The synthesis and characterization of Au3+ -modified UiO-67 metal-organic framework nanoparticles, Au3+ -NMOFs, are described. The Au3+ -NMOFs reveal dual oxidase-like and peroxidase-like activities and act as an active catalyst for the catalyzed generation of O2•- under aerobic conditions or •OH in the presence of H2 O2 . The two reactive oxygen species (ROS) agents O2•- and •OH are cooperatively formed by Au3+ -NMOFs under aerobic conditions, and in the presence of H2 O2. The Au3+ -NMOFs are applied as an effective catalyst for the generation ROS agents for antibacterial and wound healing applications. Effective antibacterial cell death and inhibition of cell proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial colonies are demonstrated in the presence of the Au3+ -NMOFs. In addition, in vivo experiments demonstrate effective wound healing of mice wounds infected by S. aureus, treated by the Au3+ -NMOFs.


Subject(s)
Metal-Organic Frameworks , Nanoparticles , Staphylococcal Infections , Animals , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Escherichia coli , Metal-Organic Frameworks/pharmacology , Mice , Reactive Oxygen Species/metabolism , Staphylococcal Infections/drug therapy , Staphylococcus aureus
7.
Biochem Biophys Res Commun ; 534: 442-449, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33248693

ABSTRACT

Ischemic stroke is a severe threat to human health due to its high recurrence, mortality, and disability rates. As such, how to prevent and treat ischemic stroke effectively has become a research hotspot in recent years. Here, we identified a novel peptide, named HsTx2 (AGKKERAGSRRTKIVMLKCIREHGH, 2 861.855 Da), derived from the scorpion Heterometrus spinifer, which showed obvious anti-apoplectic effects in rats with ischemic stroke. Results further demonstrated that HsTx2 significantly reduced formation of infarct area and improved behavioral abnormalities in ischemic stroke rats. These protective effects were likely exerted via activation of the mitogen-activated protein kinase (MAPK) signaling pathway, i.e., up-regulation of phosphorylated ERK1/2 in both rat cerebral cortex and activated microglia (AM); up-regulation of phosphorylated p38 (p-p38) in the cerebral cortex; and inhibition of phosphorylated JNK and p-p38 levels in the AM. In conclusion, this study highlights HsTx2 as a potential neuroprotective agent for stroke.


Subject(s)
Brain Ischemia/drug therapy , MAP Kinase Signaling System/drug effects , Neuroprotective Agents/therapeutic use , Scorpion Venoms/therapeutic use , Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Male , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Rats , Rats, Sprague-Dawley , Scorpion Venoms/chemistry , Scorpion Venoms/isolation & purification , Scorpions/chemistry
8.
Small ; 17(42): e2102039, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34528374

ABSTRACT

Despite their promised safety and mechanical flexibility, solvent-free polymer electrolytes suffer from low Li-ion conductivities due to poor dissociation of conducting salts and low Li+ -transference numbers due to Li+ -trapping by ether-linkages. In this work, the authors found that oxygen vacancies carried by nanosized Al2 O3 fillers preferentially promotes Li+ -conduction in poly(ethylene oxide) (PEO). These vacancies and free electrons therein, whose concentration can be tuned, effectively break up the ion pairs by weakening the Coulombic attraction within them, while simultaneously interacting with the anions, thus preferentially constraining the movement of anions. This synergistic dissociation-and-trapping effect leads to the significant and selective improvement in Li-ion conductivity. Solid state batteries built on such PEO-based electrolytes exhibits superior performance at high current density. This discovery reveals a molecular-level rationale for the long-observed phenomenon that certain inorganic nano-fillers improve ion conduction in PEO, and provides a universal approach to tailor superior polymer-based electrolytes for the next generation solid-state batteries.

9.
Nanotechnology ; 32(3): 035601, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33089831

ABSTRACT

The controllable growth of high-quality transition metal dichalcogenides (TMDs) is crucial for their device applications, which rely on the atomic and quantitative understanding of the growth mechanism of TMDs. In this work, we propose a comprehensive picture of the growth of WS2 nanosheets via Monte Carlo simulation, and an extension of diffusion-limited growth under transition state theory is developed to describe heteroepitaxy growth of WS2. Theoretical results are in good agreement with the results of chemical vapor deposition that growth temperature dominates growth processes leading to samples with various densities of vacancy defects. The vacancy defects modify the photoluminescence and ferromagnetic behavior. Our work provides a pathway toward realizing controllable physical properties in 2D materials.

10.
Int J Mol Sci ; 22(14)2021 Jul 12.
Article in English | MEDLINE | ID: mdl-34299091

ABSTRACT

The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN, PAX6, SOX2, and SOX1; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/ß-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4, HOXA7, HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2, were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis.


Subject(s)
Biomarkers/analysis , Neural Stem Cells/cytology , Neurogenesis , Neurons/cytology , Pluripotent Stem Cells/cytology , Transcriptome , Wnt Signaling Pathway , Cell Differentiation , Cells, Cultured , Humans , Leukemia Inhibitory Factor/administration & dosage , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Neurons/metabolism , Pluripotent Stem Cells/drug effects , Pluripotent Stem Cells/metabolism
11.
Angew Chem Int Ed Engl ; 60(8): 4169-4174, 2021 Feb 19.
Article in English | MEDLINE | ID: mdl-33124115

ABSTRACT

The recent developments in rechargeable aqueous batteries have witnessed a burgeoning interest in the mechanism of proton transport in the cathode materials. Herein, for the first time, we report the Grotthuss proton transport mechanism in α-MnO2 which features wide [2×2] tunnels. Exemplified by the substitution doping of Ni (≈5 at.%) in α-MnO2 that increases the energy density of the electrode by ≈25 %, we reveal a close link between the tetragonal-orthorhombic (TO) distortion of the lattice and the diffusion kinetics of protons in the tunnels. Experimental and theoretical results verify that Ni dopants can exacerbate the TO distortion during discharge, thereby facilitating the hydrogen bond formation in bulk α-MnO2 . The isolated direct hopping mode of proton transport is switched to a facile concerted mode, which involves the formation and concomitant cleavage of O-H bonds in a proton array, namely via Grotthuss proton transport mechanism. Our study provides important insight towards the understanding of proton transport in MnO2 and can serve as a model for the compositional design of cathode materials for rechargeable aqueous batteries.

12.
Gastroenterology ; 156(8): 2281-2296.e6, 2019 06.
Article in English | MEDLINE | ID: mdl-30779922

ABSTRACT

BACKGROUND & AIMS: Levels of microRNA 31 (MIR31) are increased in intestinal tissues from patients with inflammatory bowel diseases and colitis-associated neoplasias. We investigated the effects of this microRNA on intestinal inflammation by studying mice with colitis. METHODS: We obtained colon biopsy samples from 82 patients with ulcerative colitis (UC), 79 patients with Crohn's disease (CD), and 34 healthy individuals (controls) at Shanghai Tenth People's Hospital. MIR31- knockout mice and mice with conditional disruption of Mir31 specifically in the intestinal epithelium (MIR31 conditional knockouts) were given dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. We performed chromatin immunoprecipitation and luciferase assays to study proteins that regulate expression of MIR31, including STAT3 and p65, in LOVO colorectal cancer cells and organoids derived from mouse colon cells. Partially hydrolyzed alpha-lactalbumin was used to generate peptosome nanoparticles, and MIR31 mimics were loaded onto their surface using electrostatic adsorption. Peptosome-MIR31 mimic particles were encapsulated into oxidized konjac glucomannan (OKGM) microspheres, which were administered by enema into the large intestines of mice with DSS-induced colitis. Intestinal tissues were collected and analyzed by histology and immunohistochemistry. RESULTS: Levels of MIR31 were increased in inflamed mucosa from patients with CD or UC, and from mice with colitis, compared with controls. STAT3 and nuclear factor-κB activated transcription of MIR31 in colorectal cancer cells and organoids in response to tumor necrosis factor and interleukin (IL)6. MIR31-knockout and conditional-knockout mice developed more severe colitis in response to DSS and TNBS, with increased immune responses, compared with control mice. MIR31 bound to 3' untranslated regions of Il17ra and Il7r messenger RNAs (RNAs) (which encode receptors for the inflammatory cytokines IL17 and IL7) and Il6st mRNA (which encodes GP130, a cytokine signaling protein). These mRNAs and proteins were greater in MIR31-knockout mice with colitis, compared with control mice; MIR31 and MIR31 mimics inhibited their expression. MIR31 also promoted epithelial regeneration by regulating the WNT and Hippo signaling pathways. OKGM peptosome-MIR31 mimic microspheres localized to colonic epithelial cells in mice with colitis; they reduced the inflammatory response, increased body weight and colon length, and promoted epithelial cell proliferation. CONCLUSIONS: MIR31, increased in colon tissues from patients with CD or UC, reduces the inflammatory response in colon epithelium of mice by preventing expression of inflammatory cytokine receptors (Il7R and Il17RA) and signaling proteins (GP130). MIR31 also regulates the WNT and Hippo signaling pathways to promote epithelial regeneration following injury. OKGM peptosome-MIR31 microspheres localize to the colon epithelium of mice to reduce features of colitis. Transcript Profiling: GSE123556.


Subject(s)
Biomarkers/metabolism , Colitis, Ulcerative/pathology , Crohn Disease/pathology , Intestinal Mucosa/metabolism , MicroRNAs/metabolism , Regeneration/physiology , Animals , Biopsy, Needle , Case-Control Studies , China , Disease Models, Animal , Humans , Immunohistochemistry , Intestinal Mucosa/pathology , Mice , Mice, Knockout , Microspheres , RNA, Messenger/metabolism , Random Allocation , Signal Transduction
13.
Angew Chem Int Ed Engl ; 59(38): 16594-16601, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32519452

ABSTRACT

Aqueous zinc (Zn) batteries (AZBs) are widely considered as a promising candidate for next-generation energy storage owing to their excellent safety features. However, the application of a Zn anode is hindered by severe dendrite formation and side reactions. Herein, an interfacial bridged organic-inorganic hybrid protection layer (Nafion-Zn-X) is developed by complexing inorganic Zn-X zeolite nanoparticles with Nafion, which shifts ion transport from channel transport in Nafion to a hopping mechanism in the organic-inorganic interface. This unique organic-inorganic structure is found to effectively suppress dendrite growth and side reactions of the Zn anode. Consequently, the Zn@Nafion-Zn-X composite anode delivers high coulombic efficiency (ca. 97 %), deep Zn plating/stripping (10 mAh cm-2 ), and long cycle life (over 10 000 cycles). By tackling the intrinsic chemical/electrochemical issues, the proposed strategy provides a versatile remedy for the limited cycle life of the Zn anode.

14.
Small ; 15(47): e1904545, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31588653

ABSTRACT

Aqueous Zn-MnO2 batteries using mild electrolyte show great potential in large-scale energy storage (LSES) application, due to high safety and low cost. However, structure collapse of manganese oxides upon cycling caused by the conversion mechanism (e.g., from tunnel to layer structures for α-, ß-, and γ-phases) is one of the most urgent issues plaguing its practical applications. Herein, to avoid the phase conversion issue and enhance battery performance, a structurally robust novel phase of manganese oxide MnO2 H0.16 (H2 O)0.27 (MON) nanosheet with thickness of ≈2.5 nm is designed and synthesized as a promising cathode material, in which a nanosheet structure combined with a novel H+ /Zn2+ synergistic intercalation mechanism is demonstrated and evidenced. Accordingly, a high-performance Zn/MON cell is achieved, showing a high energy density of ≈228.5 Wh kg-1 , impressive cyclability with capacity retention of 96% at 0.5 C after 300 cycles, as well as exhibiting rate performance of 115.1 mAh g-1 at current rate of 10 C. To the best current knowledge, this H+ /Zn2+ synergistic intercalation mechanism is first reported in an aqueous battery system, which opens a new opportunity for development of high-performance aqueous Zn ion batteries for LSES.

15.
Am J Physiol Endocrinol Metab ; 315(4): E638-E649, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29783855

ABSTRACT

It is well known that insulin-like growth factor 1 (IGF1) acts as a trophic factor in small intestine under both physiological and pathophysiological conditions. However, it still lacks direct in vivo evidence of the functions of intestinal epithelial cell (IEC)-specific IGF1 under both normal and pathological conditions. Using IEC-specific IGF1-knockout (cKO) mice and Lgr5-eGFP-CreERT mice, we demonstrate that IEC-specific IGF1 can enhance nutrient uptake, reduce protein catabolism and energy consumption, and promote the proliferation and expansion of intestinal epithelial cells, including intestinal epithelial stem cells and intestinal secretory cells. Next, we showed that IEC-specific IGF1 renders IECs resistant to irradiation and promotes epithelial regeneration. Strikingly, transcriptome profiling assay revealed that many differentially expressed genes involved in the differentiation and maturation of lymphoid lineages were significantly suppressed in the cKO mice as compared with the control mice. We demonstrated that deletion of IGF1 in IECs enhances bacterial translocation to the mesenteric lymph nodes and liver. Furthermore, high-throughput sequencing of 16S ribosomal RNA genes of gut microbiota revealed that IEC-specific IGF1 loss profoundly affected the gut microbial composition at various levels of classification. Therefore, our findings shed light on the in vivo roles of IEC-specific IGF1 in intestinal homeostasis, epithelial regeneration, and immunity, broadening our current insights on IGF1 functions.


Subject(s)
Cell Proliferation/genetics , Epithelial Cells/cytology , Immunity, Mucosal/genetics , Insulin-Like Growth Factor I/genetics , Intestinal Mucosa/immunology , Regeneration/genetics , Stem Cells/cytology , Animals , Bacterial Translocation/genetics , Cell Lineage , Energy Metabolism/genetics , Epithelial Cells/physiology , Gastrointestinal Microbiome/genetics , Gene Expression Profiling , Gene Expression Regulation , Homeostasis , Immunity, Mucosal/immunology , Insulin-Like Growth Factor I/immunology , Insulin-Like Growth Factor I/physiology , Intestinal Absorption/genetics , Intestinal Mucosa/cytology , Liver/microbiology , Lymph Nodes/microbiology , Lymphocytes/cytology , Mesentery , Mice , Mice, Knockout , Nutrients/metabolism , Proteins/metabolism , RNA, Ribosomal, 16S , Radiation Tolerance/genetics
16.
Molecules ; 23(9)2018 Sep 12.
Article in English | MEDLINE | ID: mdl-30213067

ABSTRACT

Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously affects the life quality of patients. Because of the damage caused by DR, there is an urgent need to develop effective drugs. Folic acid, a water-soluble vitamin, is one of the vitamin B complexes. Folic acid is widely found in the meat and vegetables. In the clinic, low folic acid levels in the body may have a certain correlation with DR. However, there is no relevant basic research proving a relationship between folic acid levels and DR. The purpose of this study was therefore to investigate whether folic acid has a protective effect on the retinal vascular endothelial cells against high glucose levels. Moreover, the molecular mechanism of action of folic acid was further explored. The results showed that folic acid significantly suppressed the cell viability, tube length, migrated cells and the percentage of BrdU⁺ cells compared with the high glucose group. Moreover, folic acid decreased the mRNA expression of TEAD1 and the protein expression of TEAD1 and YAP1. These findings indicate that folic acid can protect retinal vascular endothelial cells from high glucose-induced injury by regulating the proteins in the Hippo signaling pathway.


Subject(s)
Folic Acid/pharmacology , Glucose/adverse effects , Retinal Vessels/cytology , Vitamin B Complex/pharmacology , Adaptor Proteins, Signal Transducing/metabolism , Cell Line , Cell Movement , Cell Proliferation/drug effects , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/prevention & control , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Gene Expression Regulation/drug effects , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Phosphoproteins/metabolism , Retinal Vessels/drug effects , Retinal Vessels/metabolism , Signal Transduction/drug effects , TEA Domain Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , YAP-Signaling Proteins
17.
FASEB J ; 30(10): 3474-3488, 2016 10.
Article in English | MEDLINE | ID: mdl-27383182

ABSTRACT

Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb- and Numbl-knockout mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial-to-mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53-p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.-Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis.


Subject(s)
Cell Differentiation/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Mammary Glands, Animal/metabolism , Mammary Glands, Human/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Animals , Breast/metabolism , Cell Lineage , Epithelial Cells/cytology , Epithelium/metabolism , Female , Humans , Mice, Transgenic , Muscle Cells/cytology , Muscle, Smooth/metabolism
18.
Toxicol Ind Health ; 32(9): 1693-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-25896954

ABSTRACT

The aim of this study was to reveal the effects of aluminum chloride (AlCl3) on the hepatic metabolism function and trace elements' distribution. Two hundred healthy male chickens (1 day old) were intraperitoneally administered with AlCl3 (0, 18.31, 27.47, and 36.62 mg kg(-1) day(-1) of Al(3+)) consecutively for 3 days. Then the chickens were allowed to rest for 1 day. The cycle lasted four days. The cycle was repeated 15 times (60 days). The contents of serum total protein (TP), albumin (ALB), total bilirubin (TBI), direct bilirubin (DBI), hepatic aluminum (Al), copper (Cu), iron (Fe), and zinc (Zn) were examined. The results showed that the contents of serum TP and ALB and hepatic Fe and Zn decreased and the contents of serum TBI and DBI and hepatic Al and Cu increased in the chickens with AlCl3 This indicates that chronic administration of AlCl3 impairs the hepatic metabolism function and disorders the hepatic trace elements' distribution.


Subject(s)
Aluminum Compounds/toxicity , Chemical and Drug Induced Liver Injury/metabolism , Chlorides/toxicity , Environmental Pollutants/toxicity , Liver/drug effects , Trace Elements/metabolism , Aluminum Chloride , Aluminum Compounds/administration & dosage , Aluminum Compounds/metabolism , Animals , Bilirubin/blood , Blood Proteins/analysis , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/physiopathology , Chickens/growth & development , Chlorides/administration & dosage , Chlorides/metabolism , Dose-Response Relationship, Drug , Environmental Pollutants/administration & dosage , Environmental Pollutants/metabolism , Injections, Intraperitoneal , Liver/metabolism , Liver/physiopathology , Male , Random Allocation , Serum Albumin/analysis , Tissue Distribution/drug effects , Toxicity Tests, Chronic , Toxicokinetics
19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 50(3): 235-8, 2016 Mar.
Article in Zh | MEDLINE | ID: mdl-26957241

ABSTRACT

OBJECTIVE: To analyze the correlation between skeletal muscle mass and age among check-up adults. METHODS: The study objects were those who aged 18-87 years old and came to a city hospital of Qiqihar for health examination from December, 2013 to September, 2014, excepted those with coronary heart disease, infectious disease, endocrine system disease, hypertension, anemia, cancer, liver disease, kidney disease and those carrying with heart pacemaker. A total of 1 836 respondents were finally enrolled into analysis. Appendicular Skeletal Muscle (ASM) was measured by a Body Composition Analyzer, and relative skeletal muscle index (RSMI) was calculated. The relationship among ASM, RSMI and age was assessed by linear regression analysis. The difference of height, weight, BMI, waist-hip-ratio (WHR), total muscle mass and percentage of body fat between genders were tested by t-test. The difference of ASM and total skeletal muscle mass between genders and among age groups was tested by multi-factor variance analysis. The difference of the muscle decline between genders was compared by Chi-square test. RESULTS: The total muscle mass in males was (52.22 ± 6.65) kg, which was significantly higher than that in females ((38.05 ± 4.39) kg) (t=28.20, P<0.001). ASM in 18-29, 30-39, 40-49, 50-59, 60-69, 70-87 years was (24.64 ± 3.23), (24.00 ± 3.12), (24.35 ± 3.03), (23.33 ± 2.97), (22.54 ± 2.91) and (21.40 ± 3.36) kg (F=16.12, P<0.001) in males, respectively, and (16.48 ± 3.14), (16.72 ± 1.93), (16.75 ± 1.93), (16.84 ± 2.28), (16.52 ± 2.35) and(14.70 ± 2.37)kg (F=4.38, P=0.001) in females, respectively. ASM in males ((23.72 ± 3.16) kg) was higher than that in females ((16.65 ± 2.25) kg) (t=55.97, P<0.001). There was a negative correlation between age and ASM in males after 50 years old, the regression equation was y=28.31-0.09x (P<0.001). While a negative correlation between age and ASM in females occurred after 60 years old, the regression equation was y=27.69-0.18x (P<0.001). The prevalence of low ASM was 16.85% (124/736) in females, which was significantly higher than that in males (8.73%, 96/1 100) (χ(2)=27.57, P<0.001). CONCLUSION: A negative correlation was found between age and ASM in males after 50 years old and in females after 60 years old. The prevalence of low RSMI in females was significantly higher than that in males.


Subject(s)
Body Composition , Muscle, Skeletal/physiology , Adipose Tissue , Adolescent , Adult , Aged , Aged, 80 and over , Body Mass Index , Body Weight , China , Female , Humans , Male , Middle Aged , Prevalence , Young Adult
20.
Sci Data ; 11(1): 161, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38307894

ABSTRACT

Anisodus tanguticus is a medicinal herb that belongs to the Anisodus genus of the Solanaceae family. This endangered herb is mainly distributed in Qinghai-Tibet Plateau. In this study, we combined the Illumina short-read, Nanopore long-read and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to de novo assemble the A. tanguticus genome. A high-quality chromosomal-level genome assembly was obtained with a genome size of 1.26 Gb and a contig N50 of 25.07 Mb. Of the draft genome sequences, 97.47% were anchored to 24 pseudochromosomes with a scaffold N50 of 51.28 Mb. In addition, 842.14 Mb of transposable elements occupying 66.70% of the genome assembly were identified and 44,252 protein-coding genes were predicted. The genome assembly of A. tanguticus will provide genetic repertoire to understand the adaptation strategy of Anisodus species in the plateau, which will further promote the conservation of endangered A. tanguticus resources.


Subject(s)
Genome, Plant , Plants, Medicinal , Solanaceae , Molecular Sequence Annotation , Phylogeny , Plants, Medicinal/genetics , Solanaceae/genetics , Tibet , Chromosomes, Plant
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