ABSTRACT
Psoriasis is characterized by excessive angiogenesis, with increased distortion and dilation of the dermal blood vessels. These vascular alterations are ascribed, at least in part, to the changes in dermal microvascular endothelial cell functions. However, despite the recognition of vascular normalization as an emerging strategy for the treatment of psoriasis, in-depth studies of human dermal microvascular endothelial cells (HDMECs) have been missing. The difficulty of isolation and culture of HDMECs has impeded the study of endothelial dysfunction in psoriasis. Researchers have done a great deal of work to study the abnormal characteristics of keratinocytes, fibroblasts, and leukocytes in psoriatic skin tissue. Recently, with successful isolation of HDMECs from psoriasis, great progress has been made in the elucidation of the pathogenic role of these cells in psoriasis. It is of great therapeutic significance to study the molecular mechanism of HDMECs in psoriasis. We review here the abnormalities of HDMECs in psoriasis.
Subject(s)
Endothelial Cells , Microvessels , Neovascularization, Pathologic , Psoriasis , Skin , Humans , Psoriasis/pathology , Psoriasis/physiopathology , Endothelial Cells/pathology , Endothelial Cells/metabolism , Skin/blood supply , Skin/pathology , Microvessels/pathology , Microvessels/physiopathology , Microvessels/metabolism , Animals , Signal Transduction , Phenotype , AngiogenesisABSTRACT
Autoimmune skin disease is a kind of heterogeneous disease with complicated pathogenesis. Many factors such as genetic, infectious, environmental and even psychological factors may interact together to trigger a synergistic effect for the development of abnormal innate and adaptive immune responses. Although the exact mechanisms remain unclear, recent evidence suggests that pyroptosis plays a pivotal role in the development of autoimmune skin disease. The feature of pyroptosis is the first formation of pores in cellular membranes, then cell rupture and the release of intracellular substances and pro-inflammatory cytokines, such as interleukin-1 beta (IL-1ß) and IL-18. This hyperactive inflammatory programmed cell death damages the homeostasis of the immune system and advances autoimmunity. This review briefly summarises the molecular regulatory mechanisms of pyrin domain-containing protein 3 (NLRP3) inflammasome and gasdermin family, as well as the molecular mechanisms of pyroptosis, highlights the latest progress of pyroptosis in autoimmune skin disease, including systemic lupus erythematosus, psoriasis, atopic dermatitis and systemic scleroderma and attempts to identify its potential advantages as a therapeutic target or prognostic biomarker for these diseases.
Subject(s)
Autoimmune Diseases , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Humans , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Skin Diseases/immunology , Animals , Phosphate-Binding Proteins/metabolism , Interleukin-1beta/metabolism , Scleroderma, Systemic/immunology , Lupus Erythematosus, Systemic/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Psoriasis/immunology , Psoriasis/metabolism , Autoimmunity , Interleukin-18/metabolism , Dermatitis, Atopic/immunologyABSTRACT
BACKGROUND: Psoriasis is a prevalent chronic inflammatory dermatosis characterized by excessive proliferation of keratinocytes. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly identified post-translational modification that regulates various biological processes. Abnormal Khib modification has been closely associated with the development of autoimmune diseases. OBJECTIVE: To investigate the abnormal Khib profile and its pathogenic role in psoriasis. METHODS: We utilized liquid chromatography-tandem mass spectrometry to analyze Khib-modified proteins in the epidermis of psoriasis and healthy controls. Mutated cells and mice with downregulated Ebp1Khib210 were generated to investigate its functional effects in psoriasis. RESULTS: The omic analysis revealed dysregulation of Khib modification in psoriatic lesions, exhibiting a distinct profile compared to controls. We observed the downregulation of Ebp1Khib210 in psoriatic lesions and IMQ-induced psoriatic mice. Notably, the expression of Ebp1Khib210 was upregulated in psoriatic patients following effective treatment. Decreased Ebp1Khib210 enhanced keratinocyte viability, proliferation, and survival while inhibiting apoptosis in vitro. Additionally, Pa2g4K210A mice with downregulated Ebp1Khib210 exhibited more severe psoriatic lesions and enhanced keratinocyte proliferation. Moreover, we found that Ebp1K210A mutation increased the interaction between Ebp1 and nuclear Akt, thereby inhibiting MDM2-mediated TIF-IA ubiquitination, and resulting to increased rRNA synthesis and keratinocyte proliferation. The downregulation of Ebp1Khib210 was attributed to inflammation-induced increases in HDAC2 expression. CONCLUSION: Our findings demonstrate that downregulation of Ebp1Khib210 promotes keratinocyte proliferation through modulation of Akt signaling and TIF-IA-mediated rRNA synthesis. These insights into Khib modification provide a better understanding of the pathogenesis of psoriasis and suggest potential therapeutic targets.
ABSTRACT
ErbB3-binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full-length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus. Due to the differences in the structures of these two isoforms, they have different binding partners and protein modifications. Ebp1 can function as both an oncogene and a tumor suppressor factor. However, the underlying mechanisms by which these two isoforms exert opposite functions are still not fully understood. In this review, we summarize the genes and the structures of protein of these two isoforms, protein modifications, binding partners and the association of different isoforms with diseases.
Subject(s)
Protein Isoforms , Humans , Protein Isoforms/metabolism , Animals , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/chemistry , CCAAT-Enhancer-Binding Proteins/metabolism , Neoplasms/metabolism , Protein BindingABSTRACT
Combining wave optics propagation and geometric ray tracing, the mutual optical intensity (MOI) model is extended to quantitatively simulate the propagation of partially coherent light through a kinoform lens at high speed. The MOI model can provide both a high accuracy and a high efficiency simulation. The intensity and coherence degree distributions at the focal plane are calculated using the MOI model. It is beneficial to improve the focusing capability of the kinoform lens by reducing the coherence or increasing the number of lens steps. In addition, increasing the number of steps is also beneficial to increase the photon flux and reduce the depth of focus.
ABSTRACT
The mutual optical intensity (MOI) model is a partially coherent radiation propagation tool that can sequentially simulate beamline optics and provide beam intensity, local degree of coherence and phase distribution at any location along a beamline. This paper extends the MOI model to non-ideal two-dimensional (2D) optical systems, such as ellipsoidal and toroidal mirrors with 2D figure errors. Simulation results show that one can tune the trade-off between calculation efficiency and accuracy by varying the number of wavefront elements. The focal spot size of an ellipsoidal mirror calculated with 100â ×â 100 elements gives less than 0.4% deviation from that with 250â ×â 250 elements, and the computation speed is nearly two orders of magnitude faster. Effects of figure errors on 2D focusing are also demonstrated for a non-ideal ellipsoidal mirror and by comparing the toroidal and ellipsoidal mirrors. Finally, the MOI model is benchmarked against the multi-electron Synchrotron Radiation Workshop (SRW) code showing the model's high accuracy.
ABSTRACT
Currently, the genus Paracoccus comprises 76 recognized species. Members of Paracoccus are mostly isolated from environmental, animal, and plant sources. This report describes and proposes a novel species of Paracoccus isolated from clinical specimens of the human ocular surface. We isolated two aerobic, Gram-stain-negative, non-spore-forming, coccoid or short rod-shaped, and non-motile strains (designated DK398T and DK608) from conjunctival sac swabs of two healthy volunteers. The results showed that the strains grew best under the conditions of 28°C, pH 7.0, and 1.0â% (w/v) NaCl. Sequence analysis based on the 16S rRNA gene showed that strains DK398T and DK608 were members of Paracoccus, most similar to Paracoccus laeviglucosivorans 43PT (98.54 and 98.62â%), Paracoccus litorisediminis GHD-05T (98.34 and 98.41â%), and Paracoccus limmosus NB88T (98.21 and 98.29â%). Phenotypic analysis showed that DK398T and DK608 were positive for catalase and oxidase, negative for producing N-acetyl-ß-glucosaminic acid, arginine dihydrolase, and ß-glucuronidase but positive for leucine arylamidase. The predominant isoprenoid quinone was Q-10, and the major polar lipids included phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and an unidentified glycolipid. The major fatty acids (>10%) were summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c) and C16â:â0. The meso-diaminopimelic acid was found in the cell wall peptidoglycan of DK398T. The major cell wall sugars were ribose and galactose. Based on the results of phylogenetic analyses, low (<83.22â%) average nucleotide identity, digital DNA-DNA hybridization (<26.0%), chemotaxonomic analysis, and physiological properties, strain DK398T represents a novel species of the genus Paracoccus, for which the name Paracoccus shanxieyensis sp. nov. is proposed. The type strain is DK398T (=CGMCC 1.17227T=JCM 33719T).
Subject(s)
Fatty Acids , Paracoccus , Animals , Humans , Fatty Acids/chemistry , Phospholipids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Ubiquinone/chemistry , Bacterial Typing Techniques , DNA, Bacterial/genetics , Base CompositionABSTRACT
Bistable cholesteric liquid crystals have promising application prospects in various fields, such as smart windows and displays. However, the long-term stability of two individual states is not easy to achieve, hindering their practical use. In this research, the bistable feature was enhanced by constructing a microsphere-type polymer with a liquid-crystalline epoxy/thiol monomer in negative dielectric anisotropic cholesteric liquid crystals. Spectroscopic and optical examinations revealed that either the transparent planar state or the opaque focal conic state can be maintained without the aid of an external field. Moreover, they can be switched to each other by applying a high- or low-frequency electric field. Further, factors such as the chemical structure of thiol compounds, curing temperature and curing time were investigated to explore their influences on the micro morphology of the polymer and thereby the electro-optical properties. In addition, the frequency-dependent driving scheme was analysed. Finally, bistable switching was demonstrated using an optimized sample. This energy-efficient bistable film shines light on future applications in smart windows, photonic paper and other electro-optical devices.
ABSTRACT
Combining geometric ray tracing and wave optics propagation, a new simulation model named LWF is established to calculate the full coherent X-ray propagation through a kinoform lens. The LWF model is used to analyze the X-ray propagation through long and short kinoform lenses and calculate the intensity distribution at the focal plane. When the aperture is large, the focal spot for the long kinoform lens is smaller than that for the short kinoform lens. Due to the use of the geometric ray-tracing method to calculate the beam propagation inside the kinoform lens, the LWF model takes a low number of transversal wavefront segments, i.e. a short time, to achieve high accuracy. The simulation times for the one-dimensional and two-dimensional LWF models are 0.025â s and 5.3â s, respectively, with a calculation error of less than 0.5%. The high efficiency and high accuracy make the LWF model a strong tool in designing kinoform lenses.
ABSTRACT
We successfully constructed a new class of nanoflares based on ultra-thin silica-coated gold nanoparticles (Au@SiO2) with the covalent binding of nucleic acids, which demonstrated more resistance to biothiols than that exhibited in the traditional Au-S binding strategy, for imaging the target miRNA-21 with high fidelity in living cells.
Subject(s)
Metal Nanoparticles , MicroRNAs , Gold , Silicon Dioxide , Metal Nanoparticles/toxicity , Diagnostic Imaging , MicroRNAs/geneticsABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Dermal mesenchymal stem cells (DMSCs) are not only involved in the regeneration of skin tissue, but also can regulate skin microenvironment by secreting cytokines. However, whether and how psoriatic DMSCs regulate proliferation and differentiation of keratinocytes remains unknown. OBJECTIVE: To study the effects of psoriatic DMSCs on the proliferation, differentiation, and migration of keratinocytes and the underlying mechanisms. METHODS: Following co-cultures of HaCaT cells with either psoriatic DMSCs (p-DMSCs) or DMSCs from normal volunteers (n-DMSCs), HaCaT cell proliferation was assessed using CCK-8 and EDU incorporation assay, while scratch assay and transwell assay were used to assess cell migration. qRT-PCR was used to determine expression levels of mRNA for cell proliferation (Ki-67) and differentiation (keratin 5, involucrin, and filaggrin). Western blot was used to measure expression levels of proteins associated with keratinocyte proliferation and differentiation in cultured HaCaT cells treated with or without PI3K inhibitor. ELISA assay was used to measure expression profile of stem cell factor (SCF), epidermal growth factor (EGF), and interleukin-11 (IL-11) within the co-culture supernatants. RESULTS: The results showed that p-DMSCs displayed a higher potency than n-DMSCs in stimulating proliferation, differentiation, and migration of HaCaT cells. Expression levels of PI3K and AKT proteins were markedly increased in HaCaT cells co-cultured with DMSCs versus HaCaT cell culture alone. Moreover, inhibition of the PI3K/AKT signaling pathway reversed the effect of p-DMSCs on proliferation, differentiation, and migration of HaCaT cells. Compared with n-DMSCs, the p-DMSCs showed increased secretion of IL-11, EGF, and SCF. CONCLUSION: p-DMSCs stimulate HaCaT cell proliferation, differentiation and migration via activating the PI3K/AKT signaling pathway, providing a new insight into the pathogenesis of psoriasis.
Subject(s)
Mesenchymal Stem Cells , Psoriasis , Cell Proliferation , Humans , Keratinocytes/pathology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/pathology , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/pharmacology , Psoriasis/pathology , Signal TransductionABSTRACT
OBJECTIVE: Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE. STUDY DESIGN: Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale. RESULTS: After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r = - 0.7945, p = 0.0000; r = - 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05). CONCLUSION: Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath. KEY POINTS: · Hypothermia can reduce serum levels of MBP and TNF-α in neonatal HIE.. · Hypothermia improves neurodevelopmental outcomes and reduces the rate of neurodevelopmental impairment.. · Hypothermia is a feasible and effective treatment for neonates with moderate or severe HIE..
Subject(s)
Hypothermia, Induced , Hypothermia , Hypoxia-Ischemia, Brain , Humans , Hypoxia-Ischemia, Brain/therapy , Infant , Infant, Newborn , Myelin Basic Protein , Tumor Necrosis Factor-alphaABSTRACT
Powder metallurgy introduces small structures of high-density grain boundaries into Bi2 Te3 -based alloys, which promises to enhance their mechanical and thermoelectric performance. However, due to the strong donor-like effect induced by the increased surface, Te vacancies form in the powder-metallurgy process. Hence, the as-sintered n-type Bi2 Te3 -based alloys show a lower figure of merit (ZT) value than their p-type counterparts and the commercial zone-melted (ZM) ingots. Here, boron is added to one-step-sintered n-type Bi2 Te3 -based alloys to inhibit grain growth and to suppress the donor-like effect, simultaneously improving the mechanical and thermoelectric (TE) performance. Due to the alleviated donor-like effect and the carrier mobility maintained in our n-type Bi2 Te2.7 Se0.3 alloys upon the addition of boron, the maximum and average ZT values within 298-473 K can be enhanced to 1.03 and 0.91, respectively, which are even slightly higher than that of n-type ZM ingots. Moreover, the addition of boron greatly improves the mechanical strength such as Vickers hardness and compressive strength due to the synergetic effects of Hall-Petch grain-boundary strengthening and boron dispersion strengthening. This facile and cost-effective grain boundary engineering by adding boron facilitates the practical application of Bi2 Te3 -based alloys and can also be popularized in other thermoelectric materials.
ABSTRACT
OBJECTIVE: To investigate the regulation of psoriatic dermal mesenchymal stem cells (p-DMSCs) in the expression of vascular growth factor (VEGF), and migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: A co-culture model of HUVECs and dermal mesenchymal stem cells (DMSCs)was used in this study. After 7-day co-culture, changes in expression levels of VEGF mRNA and protein in HUVECs were assessed using RT-PCR and Western Blotting, respectively. Migration and tubular formation of HUVECs were also assessed following co-culture of DMSCs and HUVECs. RESULTS: In comparison to either HUVECs alone or co-culture of n-DMSCs and HUVECs, co-culture of HUVECs and p-DMSCs significantly increased expression levels of both VEGF mRNA (p < 0.01 vs. HUVECs alone) and protein in HUVECs (p < 0.001 vs. both HUVECs alone and HUVECs co-cultured with n-DMSCs). Moreover, p-DMSCs stimulated HUVEC migration and vascular formation (p < 0.05 vs. both HUVECs alone and co-culture of n-DMSCs and HUVECs). CONCLUSION: Psoriatic DMSCs can upregulate VEGF expression, and stimulate migration and angiogenesis of HUVECs, suggesting a pathogenic role of p-DMSCs in psoriasis.
Subject(s)
Cell Communication , Human Umbilical Vein Endothelial Cells/metabolism , Mesenchymal Stem Cells/metabolism , Neovascularization, Physiologic , Psoriasis/metabolism , Skin/metabolism , Vascular Endothelial Growth Factor A/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Coculture Techniques , Humans , Mesenchymal Stem Cells/pathology , Psoriasis/pathology , Signal Transduction , Skin/pathology , Up-Regulation , Vascular Endothelial Growth Factor A/geneticsABSTRACT
Psoriasis displays both increased angiogenesis and microvascular dilation in the skin, while human dermal microvascular endothelial cells (HDMECs) are involved in angiogenesis and microvascular dilation. Whether the functions of HDMECs are altered in psoriatic skin versus healthy skin remain unknown. Here, we isolated HDMECs from the skin of 10 patients with psoriasis and 10 healthy subjects and compared angiogenesis, proliferation, migration and cell metabolism between psoriatic HDMECs and normal HDMECs. We found that the morphology of primary HDMECs was comparable between psoriatic HDMECs and normal HDMECs. After passage, psoriatic HDMECs displayed larger cell size and wider intercellular space. In addition to DiI-Ac-LDL (DiI-labelled acetylated low-density lipoprotein) uptake, expression levels of CD31, vWF (von Willebrand factor) and LYVE-1 were comparable in psoriatic HDMECs versus normal HDMECs. However, psoriatic HDMECs exhibited increased tube formation (numbers of nodes and meshes, p < 0.05) and migration (numbers of migrated cells, p < 0.001) and reductions in proliferation (growth rates, p < 0.05) and energy metabolism (oxygen consumption rate and extracellular acidification rate, p < 0.05) compared with normal HDMECs. Therefore, psoriatic HDMECs display an increased angiogenesis and migration and decreased proliferation and metabolic activity, suggesting a pathogenic role of HDMECs in psoriasis.
Subject(s)
Cell Movement , Endothelial Cells/metabolism , Microvessels , Neovascularization, Pathologic , Psoriasis , Adult , Cell Proliferation , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperproliferation. Mesenchymal stem cells (MSCs) regulate inflammation and vascular proliferation in the psoriasis lesions. Whether dermal-derived mesenchymal stem cells (DMSCs), the main MSCs in the dermis, regulate keratinocyte proliferation and apoptosis remains unknown. In the present study, we assessed the proliferation and apoptosis of keratinocytes cocultured with DMSCs isolated from either normal or psoriatic involved skin. Cell growth and apoptotic rates were determined using Cell Count Kit-8 and annexin V-FITC staining, respectively. In addition, EDU kit was also used to measure the rate of keratinocyte proliferation. Our results showed that psoriatic DMSCs (pDMSCs) were more potent than normal DMSCs (nDMSCs) in stimulating keratinocyte proliferation. In contrast, the apoptotic rate and expression levels of caspase-3 protein were lower in pDMSC-treated than nDMSC-treated keratinocytes (p < 0.001). Moreover, significantly higher contents of IL-6, IL-8, TNF-α and IFN-γ were found in the culture medium of pDMSCs than in that of nDMSCs. In conclusion, pDMSCs were more potent than nDMSCs in stimulation of keratinocyte proliferation and secretion of proinflammatory cytokines, but weaker in promoting apoptosis.
Subject(s)
Apoptosis , Cell Proliferation , Keratinocytes/metabolism , Mesenchymal Stem Cells/metabolism , Psoriasis/therapy , Adult , Female , Humans , Male , TaiwanABSTRACT
Four novel bacterial strains (ST-M6T, L-033, L-031T and Z-333) were isolated from the intestinal contents of plateau pikas (Ochotona curzoniae) collected on the Qinghai-Tibet Plateau, PR China. Cells were aerobic, non-motile, Gram-stain-positive, catalase-positive, oxidase-negative, capsuled and short-rod-shaped. Phylogenetic analyses based on the 16S rRNA gene sequences and 387 core genes indicated that the four isolates belong in the genus Microbacterium and clearly separate from recognized species. The two type strains (ST-M6T and L-031T) shared low 16S rRNA similarity, average nucleotide identity values and digital DNA-DNA hybridization relatedness with their phylogenetic neighbours (Microbacterium ginsengisoli DSM 18659T, Microbacterium hatanonis DSM 19179T, Microbacterium rhizomatis JCM 30598T, Microbacterium radiodurans CCTCC M208212T, Microbacterium oleivorans DSM 16091T and Microbacterium arborescens DSM 20754T). The genomic DNA G+C contents of strains ST-M6T and L-031T were 70.4 and 70.7 mol%, respectively. The major cellular fatty acids of strain ST-M6T were anteiso-C15â:â0, anteiso-C17â:â0 and iso-C16â:â0, in contrast to anteiso-C17â:â0, anteiso-C15â:â0 and anteiso-C17â:â1 ω9c of strain L-031T. Both type strains (ST-M6T and L-031T) were glycolate test positive and shared the following common features: MK-11 and MK-12 as major menaquinones; rhamnose, ribose, mannose and galactose as major cell-wall sugars; diphosphatidylglycerol, phosphatidylglycerol and two glycolipids as polar lipids; and ornithine, alanine, glycine and glutamic acid as cell-wall amino acids. Comparing the phenotypic, phylogenetic and chemotaxonomic features of the four strains and their related taxa, strains ST-M6T and L-031T represent two novel species of the genus Microbacterium, for which the names Microbacterium caowuchunii sp. nov. (type strain ST-M6T=CGMCC 1.16364T=DSM 104058T) and Microbacterium lushaniae sp. nov. (type strain L-031T =CGMCC 1.16363T=DSM 106170T) are proposed.
Subject(s)
Lagomorpha/microbiology , Microbacterium/classification , Phylogeny , Animals , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Gastrointestinal Contents/microbiology , Microbacterium/isolation & purification , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Tibet , Vitamin K 2/chemistryABSTRACT
The unusual dilatation of dermal capillaries and angiogenesis played important roles in psoriasis. Some genes and proteins of dermal mesenchymal stem cells (DMSCs) from psoriasis are abnormal and related to the function of endothelial cells (ECs). The present study was aimed to evaluate whether psoriatic DMSCs could affect adhesion and migration of ECs through neovascularization-related integrins in psoriasis. Human DMSCs, collected from psoriasis lesions and healthy skin, respectively, were cocultured with human umbilical vein endothelial cells (HUVECs). The expression levels of three integrins, that is, αvß3, αvß5, and α5ß1 in HUVECs were tested by quantitative real-time polymerase chain reaction and Western blot analysis. The adhesion and migration of HUVECs were detected by adhesion assay and migration assay. The results showed that in psoriasis group, the expression of αVß3 and α5ß1 of HUVECs markedly increased 2.50- and 3.71-fold in messenger RNA levels, and significantly increased 1.63- and 1.92-fold in protein levels, comparing to healthy control group (all p < .05). But ß5 was not significantly different between the two groups (p > .05). In addition, compared with control, psoriatic DMSCs promoted HUVECs adhesion by 1.62-fold and migration by 2.91-fold (all p < .05). In conclusion, psoriatic DMSCs impact HUVECs adhesion and migration by upregulating the expression of integrins αVß3 and α5ß1.
Subject(s)
Integrins/physiology , Psoriasis , Skin , Adolescent , Adult , Cell Adhesion , Child , Female , Human Umbilical Vein Endothelial Cells , Humans , Infant , Male , Mesenchymal Stem Cells , Neovascularization, Pathologic , Psoriasis/metabolism , Psoriasis/pathology , Skin/metabolism , Skin/pathology , Young AdultABSTRACT
Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.
Subject(s)
Apoptosis , Keratinocytes , Mesenchymal Stem Cells , Cell Differentiation , Cell Proliferation , HumansABSTRACT
To investigate the effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). One hundred and twelve patients with GDM in the second trimester of pregnancy were recruited from Women's Hospital, Zhejiang University School of Medicine. Patients were randomized into two groups with 56 in each group: the control group received basic nutrition support; while the dietary fiber group were given additional dietary fiber ( total dietary fiber per day) before meals in addition to basic nutrition support. Intervention for all cases lasted for 8 weeks. Fasting blood glucose and postprandial blood glucose (2 h BG) were measured every week, and oral glucose tolerance test (OGTT) was performed at 42 d postpartum to evaluate the glycemic outcomes. Perinatal outcomes were recorded. The dietary fiber intervention markedly improved 2 h BG in patients with GDM and significantly elevated the glucose compliance rate from the 3rd to 8th week compared to the control group ( <0.05 or <0.01). OGTT 2 h glucose and the incidence of impaired glucose tolerance in the dietary fiber group were significantly lower than those in the control group, while the glucose compliance rate was significantly higher than that in the control group (all <0.01). Moreover, the rates of adverse perinatal outcomes, such as premature rupture of membranes and neonatal hyperbilirubinemia were declined in the dietary fiber group (<0.05 or <0.01). Dietary fiber intervention can ameliorate hyperglycemia in GDM patients, improve perinatal outcomes and reduce the incidence of postpartum impaired glucose tolerance.