ABSTRACT
Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.
Subject(s)
Extracellular Vesicles , MicroRNAs , Satellite Cells, Skeletal Muscle , Muscle Fibers, Skeletal , Communication , MicroRNAs/genetics , Regeneration/geneticsABSTRACT
Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.
Subject(s)
MAP Kinase Signaling System , Osteonectin , Animals , Mice , Asymmetric Cell Division , Cell Differentiation , Osteonectin/genetics , Signal TransductionABSTRACT
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 TransductionABSTRACT
BACKGROUND: Lactoferrin is an active protein in breast milk that plays an important role in the growth and development of infants and is implicated as a neuroprotective agent. The incidence of depression is currently increasing, and it is unclear whether the lack of lactoferrin during lactation affects the incidence of depressive-like behavior in adulthood. RESULTS: Lack of lactoferrin feeding during lactation affected the barrier and innate immune functions of the intestine, disrupted the intestinal microflora, and led to neuroimmune dysfunction and neurodevelopmental delay in the hippocampus. When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS-TLR4 signalling pathway in the intestine and hippocampus, reduced BDNF-CREB signaling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria. CONCLUSIONS: Overall, our findings reveal that lactoferrin feeding deficient during lactation can increase the risk of depressive-like behavior in adults. The mechanism is related to the regulatory effect of lactoferrin on the development of the "microbial-intestinal-brain" axis.
Subject(s)
Lactation , Lactoferrin , Animals , Female , Mice , Intestines , Lactation/metabolism , Lactoferrin/metabolism , Milk , Signal TransductionABSTRACT
Plant polysaccharides are important for anti-aging research. Polysaccharides from Hemerocallis citrina Baroni (H. citrina) have been reported to have antioxidant activity; however, their anti-aging roles and mechanisms are not clear. In this study, we extracted polysaccharides from H. citrina by an ultrasonic-assisted water extraction-alcohol precipitation method and chemically determined the physicochemical properties such as extraction yield, content, and in vitro antioxidant properties of H. citrina polysaccharide-rich extract (HCPRE). Using Caenorhabditis elegans (C. elegans) as a model animal, the anti-aging effect of HCPRE was investigated, and the mechanism of action of HCPRE was explored by the in vivo antioxidant level assay of C. elegans and the related gene expression assay. The extraction yield of HCPRE was 11.26%, the total polysaccharide content was 77.96%, and the main monosaccharide components were glucose and galactose. In addition, HCPRE exhibited good antioxidant activity both in vitro and in vivo. Under normal thermal stress and oxidative stress conditions, being fed 1200 µg/mL of HCPRE significantly prolonged the life span of C. elegans by 32.65%, 17.71%, and 32.59%, respectively. Our study showed that HCPRE exerted an anti-aging effect on C. elegans, and its mechanism involves increasing the activities of catalase (CAT) and superoxide dismutase (SOD), reducing the level of reactive oxygen species (ROS) and regulating the expression of related genes.
Subject(s)
Caenorhabditis elegans , Hemerocallis , Animals , Antioxidants/pharmacology , Aging , Polysaccharides/pharmacology , Plant Extracts/pharmacologyABSTRACT
In a recent communication (Angew. Chem. Int. Ed. 2024, 63, e202317312), Kalita etâ al. studied In4H+ system within the frame of single-reference approximation (SRA) and found that the global energy minimum (1 a) adopted the singlet state and a planar tetracoordinate hydrogen (ptH), while the second lowest isomer (1 b) located 3.0â kcal/mol above 1 a and adopted the triplet state as well as non-planar structure with a quasi-ptH. They assessed the reliability of SRA by checking the T1-diagnostic values of coupled cluster calculations. However, according to our multi-configurational second-order perturbation theory calculations at the CASPT2(12,13)/aug-cc-pVQZ (aug-cc-pVQZ-PP for In) level, both 1 a and 1 b exhibit obvious multi-referential characters, as reflected by their largest reference coefficients of 0.928 (86.1 %) and 0.938 (88.0 %), respectively. Moreover, 1 b is 5.05â kcal/mol lower than 1 a at this level, that is, what can be observed in In4H+ system is the quasi-ptH.
ABSTRACT
OBJECTIVES: Natural autoantibodies serve as an important anti-tumorigenic component in the body. This study was thus designed to investigate whether circulating natural IgG autoantibodies against a cluster of differentiation 47 (CD47) could exert inhibitory effects on oral squamous cell carcinoma (OSCC). SUBJECTS AND METHODS: The expression levels of 13 tumor-targeted genes in three OSCC cell lines were analyzed by qPCR, and CD47 expression in OSCC tissues was also verified with IHC staining. An in-house ELISA was performed to analyze circulating anti-CD47 IgG levels in control subjects, oral benign tumor, and OSCC patients, and to detect anti-CD47 IgG-abundant plasma. Three OSCC cell lines were treated with anti-CD47 IgG-abundant and -deficient plasma, respectively, followed by the analysis of cell proliferation, apoptosis, and invasion/metastasis. RESULTS: The CD47 gene showed the highest expression among 13 genes detected in three OSCC cell lines; its expression was significantly higher in OSCC tissues than adjacent tissues. Plasma anti-CD47 IgG levels showed the differences between control subjects, oral benign tumor, and OSCC patients. Anti-CD47 IgG-abundant plasma could evidently reduce cell viability via suppressing p-AKT expression and inducing cell apoptosis and inhibit the invasion of all three OSCC cell lines. CONCLUSIONS: Natural autoantibodies against CD47 may be a potential agent for OSCC immunotherapy.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Autoantibodies , Cell Line, Tumor , Cell Proliferation/genetics , Peptides/pharmacology , Immunoglobulin G , Cell Movement/genetics , CD47 Antigen/genetics , CD47 Antigen/metabolismABSTRACT
Sonchus arvensis Linn. and Hemerocallis citrina Baroni. have been reported to improve body resistance. However, the underlying mechanism is not clear. In this study, Sonchus arvensis Linn. phenolic compounds (SAP) and Hemerocallis citrina Baroni. phenolic compounds (HCP) were extracted and their protective effects in Caenorhabditis elegans evaluated. SAP and HCP showed considerably different phenolic compositions. In the normal C. elegans model, HCP exhibited better effects in promoting growth than SAP. In the sucrose-incubated C. elegans model, both SAP and HCP showed positive effects against the high-sucrose-induced damage. In the stearic acid-incubated C. elegans model, both SAP and HCP improved lifespan, reproductive ability and growth, while HCP had a more evident effect than SAP on reproductive ability. The TGF-ß signaling pathway was confirmed to be involved in the protective effects of SAP and HCP. The antioxidant ability of SAP was also found to be related to skn-1. Our study shows that both SAP and HCP have protective effects against high sucrose- or high stearic acid-induced damage.
Subject(s)
Hemerocallis , Sonchus , Animals , Caenorhabditis elegans , Antioxidants/pharmacology , PhenolsABSTRACT
In this contribution, we review models for the lattice effects in quantum dynamics calculations on surface scattering, which is important to modeling heterogeneous catalysis for achieving an interpretation of experimental measurements. Unlike dynamics models for reactions in the gas phase, those for heterogeneous reactions have to include the effects of the surface. For manageable computational costs in calculations, the effects of static surface (SS) are firstly modeled as this is simply and easily implemented. Then, the SS model has to be improved to include the effects of the flexible surface, that is the lattice effects. To do this, various surface models have been designed where the coordinates of the surface atoms are introduced in the Hamiltonian operator, especially those of the top surface atom. Based on this model Hamiltonian operator, extensive multi-dimension quantum dynamics calculations can be performed to recover the lattice effects. Here, we first review an overview of the techniques in constructing the Hamiltonian operator, which is a sum of the kinetic energy operator (KEO) and potential energy surface (PES). Since the PES containing the coordinates of the surface atoms in a cell is still expensive, the SS model is often accepted. We consider a mathematical model, called the coupled harmonic oscillator (CHO) model, to introduce the concepts of adiabatic and diabatic representations for separating the molecule and surface. Under the adiabatic model, we further introduce the expansion model where the potential function is Taylor expanded around the optimized geometry of the surface. By an expansion model truncated at the first and second order, various coupling surface models between the molecule and surface are derived. Moreover, by further and deeply understanding the adiabatic representation, an effective Hamiltonian operator is obtained by optimizing the total wave function in factorized form. By this factorized form of wave function and effective Hamiltonian operator, the geometry phase of the surface wave function is theoretically found. This theoretical prediction may be measured by carefully designing experiments. Finally, discussions on the adiabatic representation, the PES construction, and possibility of the classical-dynamics solutions are given. Based on these discussions, a simple outlook on the dynamics of photocatalytics is finally given.
ABSTRACT
In this work, full-dimensional (9D) quantum dynamics calculations on mode-/bond-specific surface scattering of a water molecule on a copper (111) rigid surface are performed through the multilayer multiconfiguration time-dependent Hartree (ML-MCTDH) method. To easily perform the ML-MCTDH calculations on such a triatomic molecule-surface system, we first choose specific Jacobi coordinates as a set of coordinates of water. Next, to efficiently perform the 9D ML-MCTDH wavepacket propagation, the potential energy surface is transferred to a canonical polyadic decomposition form with the aid of a Monte Carlo-based method. Excitation-specific dissociation probabilities of H2O on Cu(111) are computed, and mode-/bond-specific dynamics are demonstrated by comparison with a probability curve computed for a water molecule in the ground state. The dependence of the dissociation probability of the initial state of H2O is studied, and it is found that the excitation-specific dissociation probabilities can be divided into three groups. We find that the vibrationally excited states enhance the dissociation reactivity of H2O, while the rotationally excited states hardly influence it.
ABSTRACT
As a member of the MicroRNA s (miRNAs) family, miR-421 has been widely studied in regulating the proliferation and apoptosis of cancer cells a. However, there are still no reports on miR-421 in regulating adipocyte differentiation and its related mechanisms. Accordingly, this study aimed to investigate the potential involvement of miR-421 in goat intramuscular preadipocytes (P_IMA). The expression level of miR-421 was measured via quantitative real-time PCR during goat P_IMA differentiation. And the effects of miR-421 on goat P_IMA differentiation were studied by liposome transfection, Oil red O staining and qRT-PCR. Furthermore, the miR-421 target was searched and the underlying mechanism was clarified by luciferase reporter assay and rescue experiment. Our results showed that inhibition of miR-421 could accumulation of lipid droplets by upregulation the expression level of AP2, LPL, C/EBPα and SREBP1. Further studies showed that fibroblast growth factor 13 (FGF13) was the direct target of miR-421. Knocking down of FGF13 expression could inhibit lipid droplet formation and down-regulated the expression of key adipogenic regulatory genes. In addition, the rescue experiment revealed that FGF13 is involved in miR-421-induced differentiation of goat P_IMA as a key factor. Overall, these findings indicate that miR-421 is a negative regulator in the progression of differentiation of goat P_IMA by inhibiting the expression of FGF13.
Subject(s)
Adipogenesis , MicroRNAs , Animals , Adipogenesis/genetics , Adipocytes/metabolism , Goats/genetics , Goats/metabolism , Cell Differentiation/genetics , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Lactoferrin (Ltf), a naturally active glycoprotein, possesses anti-inflammatory, anti-microbial, anti-tumor, and immunomodulatory activities. Many published studies have indicated that Ltf modulates the proliferation of stem cells. However, the role of Ltf in the proliferation of satellite cells, an important cell type in muscle regeneration, has not yet been reported. Here, by using Ltf systemic knockout mice, we illustrate the role of Ltf in skeletal muscle. Results shows that Ltf deficiency impaired proliferation of satellite cells (SCs) and the regenerative capability of skeletal muscle. Mechanistic studies showed that ERK1/2 phosphorylation was significantly downregulated after Ltf deletion in SCs. Simultaneously, the cell cycle-related proteins cyclin D and CDK4 were significantly downregulated. Intervention with exogenous recombinant lactoferrin (R-Ltf) at a concentration of 1000 µg/mL promoted proliferation of SCs. In addition, intraperitoneal injection of Ltf effectively ameliorated the skeletal muscle of mice injured by 1.2% BaCl2 solution. Our results suggest a protective effect of Ltf in the repair of skeletal muscle damage. Ltf holds promise as a novel therapeutic agent for skeletal muscle injuries.
Subject(s)
Lactoferrin , MAP Kinase Signaling System , Animals , Cell Cycle Proteins/metabolism , Cell Proliferation/physiology , Down-Regulation , Lactoferrin/deficiency , Lactoferrin/metabolism , Lactoferrin/pharmacology , Mice , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Recombinant Proteins/pharmacology , Signal TransductionABSTRACT
Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after cardiotoxin injury resulted in improved mitochondrial function, increased energy expenditure, and enhanced thermogenesis. Importantly, it was found that interleukin-6 (IL-6), as a myokine, participates in this process. Mechanistically, Islr interacts with NADH: Ubiquinone Oxidoreductase Core Subunit S2 (Ndufs2) to regulate IL-6 signaling; consequently, Islr functions as a brake that prevents IL-6 from promoting BAT activity. Together, these findings reveal a previously unrecognized mechanism for muscle-BAT cross talk driven by Islr, Ndufs2, and IL-6 to regulate energy homeostasis, which may be used as a potential therapeutic target in obesity.
Subject(s)
Adipose Tissue, Brown , Interleukin-6 , Adipose Tissue, Brown/metabolism , Animals , Cell Differentiation , Energy Metabolism , Homeostasis , Immunoglobulins/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Leucine/metabolism , Mice , Muscle, Skeletal/metabolism , NADH Dehydrogenase/metabolism , ThermogenesisABSTRACT
Providing access to highly diverse polymer structures by multicomponent reactions is highly desirable; efficient Meldrum's acid-based multicomponent reactions, however, have been rarely highlighted in polymer chemistry. Here, the three-component reaction of Meldrum's acid, indole, and aldehyde is introduced into polymer synthesis. Direct multicomponent polymerization of Meldrum's acid, dialdehyde, and diindole can perform under mild conditions, resulting in complex Meldrum's acid-containing polymers with well-defined structures, and high molecular weights. Additionally, nearly quantitative postpolymerization modification can also perform via this Meldrum's acid-based multicomponent reaction. These results indicate that Meldrum's acid-based multicomponent reaction will be a potential tool to prepare novel polymers.
Subject(s)
Dioxanes , Polymers , Aldehydes , PolymerizationABSTRACT
Previous studies have shown that melatonin (MT) can ameliorate vitrification-inflicted damage in mouse germinal vesicle (GV) oocytes, however, the key mechanistic basis of this improvement still remains poorly understood. This study was conducted to investigate whether MT can improve in vitro developmental potential of vitrified-warmed GV oocytes through its receptors. The fresh oocytes were randomly divided into four groups: untreated (control group, F), vitrified by open-pulled straw method (vitrification group, V), vitrification group with 100 nmol/L MT supplementation (vitrification + MT group, VM), and with 100 nmol/L MT plus 100 nmol/L luzindole administration (vitrification + MT + luzindole group, VML) or with 50 nmol/L ramelteon addition (vitrification + ramelteon group; VR). After warming, oocytes were cultured in vitro, and MT receptors (MTRs), MAD2 (mitotic arrest deficient 2), Securin and CyclinB1 protein levels and spindle morphology were evaluated. The ratio of oocytes developed to the metaphase I (MI) and metaphase II (MII) stages was also assessed. The results showed that after vitrification-warming, the in vitro maturation rate of GV oocytes was significantly lower compared to the control (F) group. Vitrification also significantly impaired the spindle morphology, decreased the protein level of MTRs and Securin, and decreased MAD2 levels in MI oocytes. However, when MT or ramelteon (MTRs agonist) were added (group wise) to warming and maturation media, the maturation rate of GV oocytes was significantly increased, the normal proportion of the spindle morphology increased, and the expression level of MAD2 increased in their resulting MI oocytes compared to the vitrification group. However, following addition of both MT and ramelteon, the maturation rate of GV oocyte showed no significant difference between VML and vitrification groups. The spindle morphology and MAD2 levels in MI oocytes were comparable to the vitrification group but differed significantly from the VM group. Taken together, finding of the present study shows that MT (100 nmol/L) can ameliorate the in vitro maturation of vitrified-warmed mouse GV oocytes, potentially by improving the spindle morphology, modulating MAD2 protein level and promoting the development of MI stage oocytes through MTRs.
Subject(s)
Melatonin , Animals , Cryopreservation/methods , In Vitro Oocyte Maturation Techniques , Melatonin/pharmacology , Metaphase , Mice , Oocytes , Random Allocation , VitrificationABSTRACT
The sugar distribution mechanism in fruits has been the focus of research worldwide; however, it remains unclear. In order to elucidate the relevant mechanisms in grape berries, the expression, localization, function, and regulation of three sucrose transporters were studied in three representative Vitis varieties. Both SUC11 and SUC12 expression levels were positively correlated with sugar accumulation in grape berries, whereas SUC27 showed a negative relationship. The alignment analysis and sucrose transport ability of isolated SUCs were determined to reflect coding region variations among V. vinifera, V. amurensis Ruper, and V. riparia, indicating that functional variation existed in one SUT from different varieties. Furthermore, potentially oligomerized abilities of VvSUCs colocalized in the sieve elements of the phloem as plasma membrane proteins were verified. The effects of oligomerization on transport properties were characterized in yeast. VvSUC11 and VvSUC12 are high-affinity/low-capacity types of SUTs that stimulate each other by upregulating Vmax and Km, inhibiting sucrose transport, and downregulating the Km of VvSUC27. Thus, changes in the distribution of different SUTs in the same cell govern functional regulation. The activation and inhibition of sucrose transport could be achieved in different stages and tissues of grape development to achieve an effective distribution of sugar.
Subject(s)
Fruit/metabolism , Membrane Transport Proteins/metabolism , Plant Proteins/metabolism , Sucrose/metabolism , Vitis/metabolism , Biological Transport , Fruit/growth & development , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/genetics , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Multimerization , Structure-Activity Relationship , Vitis/growth & developmentABSTRACT
In this work, Gaussian process regression (GPR) for fitting a high-dimensional potential energy surface (PES) is revisited and implemented to construct the PES of OH + HO2 â O2 + H2O. Using mixed kernel function and optimized distribution of the training database, only â¼3 × 103 energy points are needed to approach convergence, which implies the power of GPR in saving lots of computational cost. Moreover, the convergence of the GPR PES is inspected, leading to discussions on the advantages of the GPR fitting approach. By the segmented strategy [Meng et al., J. Chem. Phys. 144, 154312 (2016)], a GPR PES with a fitting error of â¼21 meV is constructed using â¼4600 energy points at the CCSD(T)-F12a/aug-cc-pVTZ level. The rate coefficients are then computed through the ring-polymer molecular dynamics (RPMD) method. An agreement between the present RPMD calculations and the previous observations is found, implying the accuracy of the present calculations. Moreover, the unusual feature of the Arrhenius curve is interpreted by a coupled harmonic oscillator model [Q. Meng, J. Phys. Chem. A 122, 8320 (2018)] together with a simple kinetics model.
ABSTRACT
BACKGROUND: Natural antibodies are critical components for maintaining homeostasis of the immune system. Regulatory T (Treg) cells have indispensable effects on immunosuppressive function and peripheral immune tolerance. Both CD25 and FOXP3 are specifically expressed in Treg cells and their natural antibodies may protect against the development of type-2 diabetes (T2D). The present study aimed to test whether circulating antibodies against CD25 and FOXP3 were altered in first-episode patients with T2D. METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect the levels of plasma IgG antibodies against five linear peptide antigens with three derived from CD25 (named CD25a, CD25b, CD25c) and two derived from FOXP3 (called FOXP3a and FOXP3b) among 200 first-episode patients with T2D and 220 healthy controls. RESULTS: Mann-Whitney U test showed a significant decrease in anti-CD25a IgG levels in patients with T2D as compared with the healthy controls (Z = -3.438, p = 0.0006), male patients mainly contributing to the decreased levels of anti-CD25a IgG levels (Z = -3.065, p = 0.002). The other four IgG tests demonstrated a lower level of plas-ma IgG antibodies in the patient group than the control group, but failed to show statistical significance (p > 0.01). ROC curve analysis indicated that the anti-CD25a IgG assay had the best sensitivity of 19.5% against the specificity of 90%. CONCLUSIONS: Decreased anti-CD25 IgG levels in the circulation may represent a reduction in the number of Treg cells and detection of such antibodies may be beneficial to the understanding of immunological changes in T2D patients.
Subject(s)
Diabetes Mellitus, Type 2 , T-Lymphocytes, Regulatory , Diabetes Mellitus, Type 2/diagnosis , Enzyme-Linked Immunosorbent Assay , Forkhead Transcription Factors , Humans , Immunoglobulin G , Interleukin-2 Receptor alpha Subunit , MaleABSTRACT
Sucrose is the predominant form of sugar transported from photosynthetic (source) to non-photosynthetic (sink) organs in higher plants relying on the transporting function of sucrose transporters (SUTs or SUCs). Many SUTs have been identified and characterized in both monocots and dicots. However, the function of sucrose transporters (SUTs or SUCs) from Vitis is not clear. As the world's most planted grape species, Vitis vinifera owns three sucrose transport activity verified SUTs. In this study, we constructed three kinds of VvSUC (Vitis vinifera SUC)-overexpressing transgenic Arabidopsis. VvSUC-overexpressing transgenic Arabidopsis was cultured on sucrose-supplemented medium. VvSUC11- and VvSUC12-overexpressing lines had similar thrived growth phenotypes, whereas the size and number of leaves and roots from VvSUC27-overexpressing lines were reduced compared with that of WT. When plants were cultured in soil, all SUT transgenic seedlings produced more number of leaves and siliques, resulting in higher yield (38.6% for VvSUC12-transformants) than that of WT. Besides, VvSUC27-transformants and VvSUC11-transformants enhanced drought resistance in Arabidopsis, providing a promising target for crop improvement.
Subject(s)
Adaptation, Biological/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Droughts , Genes, Plant , Sucrose/economics , Vitis/genetics , Amino Acid Sequence , Arabidopsis/growth & development , Biological Transport , Gene Expression Regulation, Plant , Phenotype , Plant Development/genetics , Sucrose/metabolismABSTRACT
The rapid developments of gene therapy are benefit from the construction of efficient gene vectors, which help therapy genes efficiently overcome the barriers in the transport and transfection. Condensing DNA into nanoparticles is a crucial role in gene transfection, and the electrostatic interactions of synthetic cationic liposomes and cationic polymers with DNA are generally used for condensing DNA. Recent research has shown that the introduction of the hydrophobic interaction, hydrogen bonding, and coordinative interactions to the gene delivery vectors is also very important for DNA condensation, delivery, and transfection. This review focuses on the four types of interactions in condensed DNA nanoparticles, which could provide a new perspective for improving gene transfection efficacy.