ABSTRACT
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1É expression to enhance the activities of VEGF and SDF-1É, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1É-VEGF/SDF-1É pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.
Subject(s)
Diabetes Mellitus, Experimental , Endothelial Progenitor Cells , Growth Differentiation Factors , Wound Healing , Animals , Humans , Mice , Bone Morphogenetic Proteins/metabolism , Chemokine CXCL12/drug effects , Chemokine CXCL12/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/pathology , Growth Differentiation Factors/therapeutic use , Growth Differentiation Factors/metabolism , Neovascularization, Physiologic , Vascular Endothelial Growth Factor A/drug effects , Vascular Endothelial Growth Factor A/metabolism , Wound Healing/drug effects , Recombinant Proteins/metabolism , Recombinant Proteins/therapeutic use , Hypoxia-Inducible Factor 1, alpha Subunit/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolismABSTRACT
Escherichia coli is the most widely used bacterium in prokaryotic expression system for the production of recombinant proteins. In BL21 (DE3), the gene encoding the T7 RNA polymerase (T7 RNAP) is under control of the strong lacUV5 promoter (PlacUV5), which is leakier and more active than wild-type lac promoter (PlacWT) under certain growth conditions. These characteristics are not advantageous for the production of those recombinant proteins with toxic or growth-burdened. On the one hand, leakage expression of T7 RNAP leads to rapid production of target proteins under non-inducing period, which sucks resources away from cellular growth. Moreover, in non-inducing or inducing period, high expression of T7 RNAP production leads to the high-production of hard-to-express proteins, which may all lead to loss of the expression plasmid or the occurrence of mutations in the expressed gene. Therefore, more BL21 (DE3)-derived variant strains with rigorous expression and different expression level of T7 RNAP should be developed. Hence, we replaced PlacUV5 with other inducible promoters respectively, including arabinose promoter (ParaBAD), rhamnose promoter (PrhaBAD), tetracycline promoter (Ptet), in order to optimize the production of recombinant protein by regulating the transcription level and the leakage level of T7 RNAP. Compared with BL21 (DE3), the constructed engineered strains had higher sensitivity to inducers, among which rhamnose and tetracycline promoters had the lowest leakage ability. In the production of glucose dehydrogenase (GDH), a protein that causes host autolysis, the engineered strain BL21 (DE3::ara) exhibited higher biomass, cell survival rate and foreign protein expression level than that of BL21 (DE3). In addition, these engineered strains had been successfully applied to improve the production of membrane proteins, including E. coli cytosine transporter protein (CodB), the E. coli membrane protein insertase/foldase (YidC), and the E. coli F-ATPase subunit b (Ecb). The engineered strains constructed in this paper provided more host choices for the production of recombinant proteins.
Subject(s)
Cloning, Molecular/methods , DNA-Directed RNA Polymerases/genetics , Escherichia coli/genetics , Gene Expression Regulation, Bacterial , Recombinant Proteins/biosynthesis , Viral Proteins/genetics , Genetic Vectors , Membrane Transport Proteins/genetics , Protein Transport , Recombinant Proteins/geneticsABSTRACT
The intensity ratio of the 2D band to the G band, I2D /IG , is a good criterion in selecting high quality monolayer graphene samples; however, the evaluation of the ultimate value of I2D /IG for intrinsic monolayer graphene is a challenging yet interesting issue. Here, an interesting tension-induced Raman enhancement phenomenon is reported in supported graphene membranes, which show a transition from the corrugated state to the stretched state in the vicinity of wells. The I2D /IG of substrate-supported graphene membranes near wells are significantly enhanced up to 16.74, which is the highest experimental value to the best of knowledge, increasing by more than 600% when the testing points approach the well edges.The macroscopic origin of this phenomenon is that corrugated graphene membranes are stretched by built-in tensions. A lattice dynamic model is proposed to successfully reveal the microscopic mechanism of this phenomenon. The theoretical results agree well with the experimental data, demonstrating that tensile stresses can depress the amplitude of in-plane vibration of sp2 -bonded carbon atoms and result in the decrease in the G band intensity. This work can be helpful in furthering the development of the method of suppressing small ripples in graphene and acquiring ultraflat 2D materials.
ABSTRACT
The effects of ß adrenergic receptors (ß-ARs) and p38 mitogen-activated protein kinases (MAPK) pathways on cardiosphere-derived cells (CDCs) are largely unknown. This study aimed to investigate the roles of ß-ARs and p38MAPK pathways on the proliferation, apoptosis, and differentiation capacity of CDCs. The CDCs were treated with ß1-AR blocker (Met group), ß2-AR antagonist (ICI group), and p38MAPK inhibitor (SB group), non-selective ß-AR blocker (PRO group), and ß-AR agonist (ISO group). The viability, apoptotic rate and differentiation status of CDCs were determined by MST-1 assay, flow cytometery, and Western blot, respectively. The CDCs viability significantly reduced in ICI group (all P < 0.05), and SB group had a significant high viability after 48 h treatment (P < 0.05). Compared with control group, all treated groups had a low apoptotic rate. After treatment for 72 h, ISO treatment elevated the expression of Nkx2.5, and could partially or fully attenuate the inhibitory effects of ß-AR antagonists and/or p38MAPK inhibitor. A similar overall trend of protein expression levels among all groups could be observed between protein pairs of cTnT and ß1-AR as well as c-Kit and ß2-AR, respectively. These results suggested that ß-ARs and p38MAPK signaling pathways play crucial roles in the proliferation and differentiation of CDCs. Our findings should be helpful for better understanding the molecular mechanism underlying the physiological processes of CDCs.
Subject(s)
Myocytes, Cardiac/cytology , Receptors, Adrenergic, beta-1/metabolism , Receptors, Adrenergic, beta-2/metabolism , Spheroids, Cellular/cytology , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Apoptosis , Cell Culture Techniques , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Imidazoles/pharmacology , Isoproterenol/pharmacology , MAP Kinase Signaling System/drug effects , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Propanolamines/pharmacology , Propranolol/pharmacology , Pyridines/pharmacology , Rats , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolismABSTRACT
BACKGROUND: Hyperbaric oxygen (HBO) improves skin flap function and inhibits partial necrosis induced by ischemia-reperfusion (I/R) injury. Our study aimed to evaluate the mechanism underlying HBO regulation of the antiapoptosis factors associated with I/R injury of skin flaps. METHODS: The rats were divided into sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was measured with laser Doppler flowmeters. Tissue morphology and apoptosis were subsequently assessed based on hematoxylin-eosinhe and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Protein expression of phosphorylated apoptosis signal-regulating kinase 1 (pASK-1), phosphorylated c-Jun N-terminal kinase (pJNK), B-cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) was examined by immunodetection, and Bcl-2 messenger RNA expression was detected by quantitative polymerase chain reaction. In addition, caspase-3 activity was also measured. RESULTS: The result of microcirculation analysis showed that the survival and blood perfusion rates significantly increased in the skin flap after HBO exposure. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining revealed that cell apoptosis was significantly attenuated in the HBO group. Furthermore, HBO preconditioning increased the expression of Bcl-2 and inhibited pASK-1, pJNK, and Bax expression as determined by both immunohistochemistry and Western blot. Caspase-3 activity and the Bax/Bcl-2 ratio declined in the HBO group. CONCLUSIONS: HBO preconditioning effectively ameliorates I/R injury by regulating the apoptosis signal-regulating kinase 1 and/or c-Jun N-terminal kinase pathway and anti- and proapoptosis factors.
Subject(s)
Apoptosis , Hyperbaric Oxygenation , Ischemic Preconditioning/methods , Reperfusion Injury/prevention & control , Skin/blood supply , Animals , Caspase 3/metabolism , Disease Models, Animal , MAP Kinase Kinase Kinase 5/metabolism , Male , Proto-Oncogene Proteins c-bcl-2/metabolism , Random Allocation , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Skin/metabolism , Skin/pathology , bcl-2-Associated X Protein/metabolismABSTRACT
Common wheat (Triticum aestivum L.) is a global staple food, while nitrogen (N) limitation severely hinders plant growth, seed yield, and grain quality of wheat. Genetic variations in the responses to low N stresses among allohexaploid wheat (AABBDD, 2n = 6x = 42) genotypes emphasize the complicated regulatory mechanisms underlying low N tolerance and N use efficiency (NUE). In this study, hydroponic culture, inductively coupled plasma mass spectrometry, noninvasive microtest, high-performance liquid chromatography, RNA-seq, and bioinformatics were used to determine the differential growth performance, ionome and phytohormone profiles, and genome-wide expression profiling of wheat plants grown under high N and low N conditions. Transcriptional profiling of NPFs, NRT2s, CLCs, SLACs/SLAHs, AAPs, UPSs, NIAs, and GSs characterized the core members, such as TaNPF6.3-6D, TaNRT2.3-3D, TaNIA1-6B, TaGLN1;2-4B, TaAAP14-5A/5D, and TaUPS2-5A, involved in the efficient transport and assimilation of nitrate and organic N nutrients. The low-N-sensitivity wheat cultivar XM26 showed obvious leaf chlorosis and accumulated higher levels of ABA, JA, and SA than the low-N-tolerant ZM578 under N limitation. The TaMYB59-3D-TaNPF7.3/NRT1.5-6D module-mediated shoot-to-root translocation and leaf remobilization of nitrate was proposed as an important pathway regulating the differential responses between ZM578 and XM26 to low N. This study provides some elite candidate genes for the selection and breeding of wheat germplasms with low N tolerance and high NUE.
Subject(s)
Plant Growth Regulators , Triticum , Triticum/genetics , Triticum/metabolism , Plant Growth Regulators/metabolism , Nitrogen/metabolism , Nitrates/metabolism , Plant BreedingABSTRACT
Primula amethystina subsp. argutidens (Franchet) W. W. Smith & H. R. Fletcher (1942) is a blooming plant of the family Primulaceae. Here, we sequenced, assembled, and annotated the complete chloroplast (cp) genome of P. amethystina subsp. argutidens. The cp genome of P. amethystina subsp. argutidens is 151,560 bp in length with a GC content of 37%. The assembled genome has a typical quadripartite structure, containing a large single-copy (LSC) region of 83,516 bp, a small single-copy (SSC) region of 17,692 bp, and a pair of inverted repeat (IR) regions of 25,176 bp. The cp genome contains 115 unique genes, including 81 protein-coding genes, four rRNA genes, and 30 tRNA genes. Phylogenetic analysis showed that P. amethystina subsp. argutidens was closely related to P. amethystina.
ABSTRACT
Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.
Subject(s)
Electroacupuncture , Guanine Nucleotide Exchange Factors , Ion Channels , Irritable Bowel Syndrome , Animals , Guanine Nucleotide Exchange Factors/genetics , Hyperalgesia/etiology , Hyperalgesia/metabolism , Hyperalgesia/therapy , Ion Channels/genetics , Irritable Bowel Syndrome/therapy , Mice , Serotonin/metabolismABSTRACT
Machine learning methods are a novel way to predict and rank donors' willingness to donate blood and to achieve precision recruitment, which can improve the recruitment efficiency and meet the challenge of blood shortage. We collected information about experienced blood donors via short message service (SMS) recruitment and developed 7 machine learning-based recruitment models using PyCharm-Python Environment and 13 features which were described as a method for ranking and predicting donors' intentions to donate blood with a floating number between 0 and 1. Performance of the prediction models was assessed by the Area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score in the full dataset, and by the accuracy in the four sub-datasets. The developed models were applied to prospective validations of recruiting experienced blood donors during two COVID-19 pandemics, while the routine method was used as a control. Overall, a total of 95,476 recruitments via SMS and their donation results were enrolled in our modelling study. The strongest predictor features for the donation of experienced donors were blood donation interval, age, and donation frequency. Among the seven baseline models, the eXtreme Gradient Boosting (XGBoost) and Support vector machine models (SVM) achieved the best performance: mean (95%CI) with the highest AUC: 0.809 (0.806-0.811), accuracy: 0.815 (0.812-0.818), precision: 0.840 (0.835-0.845), and F1 score of XGBoost: 0.843 (0.840-0.845) and recall of SVM: 0.991 (0.988-0.994). The hit rate of the XGBoost model alone and the combined XGBoost and SVM models were 1.25 and 1.80 times higher than that of the conventional method as a control in 2 recruitments respectively, and the hit rate of the high willingness to donate group was 1.96 times higher than that of the low willingness to donate group. Our results suggested that the machine learning models could predict and determine the experienced donors with a strong willingness to donate blood by a ranking score based on personalized donation data and demographical details, significantly improve the recruitment rate of blood donors and help blood agencies to maintain the blood supply in emergencies.
Subject(s)
Blood Donors , COVID-19 , Humans , COVID-19/epidemiology , Machine Learning , Intention , Disease OutbreaksABSTRACT
In the title compound, {[Zn(C(4)H(4)O(5))(C(10)H(8)N(2))]·2H(2)O}(n), the Zn(II) ion displays a distorted tetra-gonal-pyramidal coordination environment with one hy-droxy O and three carboxyl-ate O atoms from three malate anions, and the one remaining position occupied by an N atom from a 4,4'-bipyridine ligand. The pyridine rings of the 4,4'-bipyridine ligand are twisted with respect to each other by a dihedral angle of 35.8â (2)°. The uncoordinated water mol-ecules are linked to the complex mol-ecules by O-Hâ¯O hydrogen bonds. Each malate anion forms four coordination bonds with three Zn atoms, establishing a layer structure parallel to the ac plane. Adjacent layers are further linked via O-Hâ¯N hydrogen bonding. π-π stacking between the pyridine rings [face-to-face distance = 3.651â (3)â Å] occurs in the crystal structure.
ABSTRACT
The title compound, [Co(C(2)H(8)N(2))(3)](2)[SiMo(8)V(4)O(40)(VO)(2)]·6H(2)O, was prepared under hydro-thermal conditions. The asymmetric unit consists of a transition metal complex [Co(en)(3)](3+) cation (en is ethyl-enediamine), one half of an [SiMo(8)V(4)O(40)(VO)(2)](6-) heteropolyanion, two solvent water mol-ecules in general positions and two half-mol-ecules of water located on a mirror plane. In the complex cation, the Co(3+) ion is in a distorted octa-hedral coordination environment formed by six N atoms of the three chelating en ligands. One of the en ligands exhibits disorder of its aliphatic chain over two sets of sites of equal occupancy. The [SiMo(8)V(4)O(40)(VO)(2)](6-) heteropolyanion is a four-electron reduced bivanadyl-capped α-Keggin-type molybdenum-vanadium-oxide cluster. In the crystal, it is located on a mirror plane, which results in disorder of the central tetra-hedral SiO(4) group: the O atoms of this group occupy two sets of sites related by a mirror plane. Furthermore, all of the eight µ(2)-oxide groups are also disordered over two sets of sites with equal occupancy. There are extensive inter-molecular N-Hâ¯O hydrogen bonds between the complex cations and inorganic polyoxidoanions, leading to a three-dimensional supra-molecular network.
ABSTRACT
The title compound, [AlCu(3)W(12)O(40)(C(2)H(8)N(2))(6)(H(2)O)(3)], was prepared under hydro-thermal conditions. The Cu(2+) ion displays an elongated octa-hedral geometry defined by one bridging O atom from the polyoxidoanion and a coordinated water mol-ecule in axial positions and four N atoms of the two chelating ethyl-enediamine (en) ligands in equatorial positions. The one-electron reduced [AlW(12)O(40)](6-) anion coordinates three [Cu(en)(H(2)O)](2+) fragments, generating a neutral tri-supported Keggin-type polyoxidometalate (POM). This tri-supported POM is located in a special position of [Formula: see text] symmetry and therefore O atoms from the central AlO(4) tetra-hedron are disordered over two sets of sites. Disorder is also observed for three other bridging O atoms of the POM. In the crystal, mol-ecules are connected via N-Hâ¯O and O-Hâ¯O hydrogen bonds, forming a three-dimensional framework.
ABSTRACT
In the title compound, C(25)H(18)N(2)O(2), the pyrazolo-[5,1-a]iso-quin-oline ring system is approximately planar [maximum deviation = 0.027â (2)â Å] and is oriented at dihedral angles of 57.22â (6) and 71.36â (7)° with respect to the two phenyl rings. The phenyl rings are twisted to each other by a dihedral angle of 66.33â (8)°. A weak intra-molecular C-Hâ¯O hydrogen bond occurs. In the crystal, weak C-Hâ¯π inter-actions are present.
ABSTRACT
We report here a Ru-catalyzed enantioselective synthesis of biaryl-bridged NH lactams through asymmetric reductive amination and a spontaneous ring-closing cascade from keto esters and NH4OAc with H2 as reductant. The reaction features broad substrate generality and high enantioselectivities (up to >99% ee). To showcase the practical utility, a highly enantioselective synthesis of 5-ethylindolobenzazepinone C, a promising antimitotic agent, has been rapidly completed. Furthermore, the amide group in the products enables versatile elaborations through directed C-H functionalization.
Subject(s)
Amides/chemistry , Lactams/chemical synthesis , Amination , Catalysis , Lactams/chemistry , Molecular StructureABSTRACT
A novel modified polyoxometalate, {PMo12O40[Cu(2,2'-bpy)]}[Cu(2,2'-bpy)(en)(H2O)]2 [2,2'-bpy is 2,2'-bipyridyl (C10H8N2) and en is ethylenediamine (C2H8N2)], has been synthesized hydrothermally and structurally characterized by elemental analysis, TG, IR, XPS and single-crystal X-ray diffraction. The structural analysis reveals that the compound contains the reduced Keggin polyanion [PMo12O40]6- as the parent unit, which is monocapped by [Cu(2,2'-bpy)]2+ fragments via four bridging O atoms on an {Mo4O4} pit and bi-supported by two [Cu(2,2'-bpy)(en)(H2O)]2+ coordination cations simultaneously. There exist strong intramolecular π-π stacking between the capping and supporting units, which play a stabilizing role during the crystallization of the compound. Adjacent POM clusters are further aggregated to form a three-dimensional supramolecular network through noncovalent forces, hydrogen bonding and π-π stacking interactions. In addition, the photocatalytic properties were investigated in detail, and the results indicated that the compound can be used as a photocatalyst towards the decomposition of the organic pollutant methylene blue (MB).
ABSTRACT
Nav1.1 and Nav1.2 are the voltage-gated sodium channel alpha subunit1 and 2, encoded by the genes of SCN1A and SCN2A. Previous studies have shown that chronic cerebral hypoperfusion (CCH) could induce neuropathological and cognitive impairment and increased total Nav1.1 and Nav1.2protein levels, yet the detailed mechanisms are not fully understood. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of dementia. miR-132 is known to play a key role in neurodegenerative disease. Here, we determined that miR-132 regulates Nav1.1 and Nav1.2 under CCH state. In this study, the expression of miR-132 was decreased in both the hippocampus and cortex of ratsfollowing CCH generated by bilateral common carotid artery occlusion (2VO). Lentiviral-mediated overexpression of miR-132 ameliorated dementia vulnerability induced by 2VO. At the molecular level, miR-132 repressed the increased protein expression of Nav1.1 and Nav1.2 in both the hippocampus and cortex induced by 2VO. MiR-132 suppressed, while AMO-miR-132 enhanced, the level of Nav1.1 and Nav1.2 in primary cultured neonatal rat neurons (NRNs) detected by both western blot analysis and immunofluorescence analysis. Results obtained by dual luciferase assay showed that overexpression of miR-132 inhibited the expression of Nav1.1 and Nav1.2 in human embryonic kidney 293 (HEK293T) cells. Additionally, binding-site mutation failed to influence Nav1.1 and Nav1.2, indicating that Nav1.1 and Nav1.2 are potential targets for miR-132. Taken together, our findings demonstrated that miR-132 protects against CCH-induced learning and memory impairments by down-regulating the expression of Nav1.1 and Nav1.2, and SCN1A and SCN2A are the target genes of miR-132.
Subject(s)
Cerebral Cortex/metabolism , Hippocampus/metabolism , MicroRNAs/metabolism , NAV1.1 Voltage-Gated Sodium Channel/genetics , NAV1.1 Voltage-Gated Sodium Channel/metabolism , NAV1.2 Voltage-Gated Sodium Channel/metabolism , Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Cerebral Cortex/blood supply , Cerebral Cortex/pathology , Cerebrovascular Circulation/physiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Dementia/metabolism , Dementia/pathology , Disease Models, Animal , HEK293 Cells , Hippocampus/blood supply , Hippocampus/pathology , Humans , Male , MicroRNAs/genetics , NAV1.2 Voltage-Gated Sodium Channel/genetics , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurons/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley , Temporal Lobe/pathologyABSTRACT
BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD. METHODS: Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination. RESULTS: The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively). CONCLUSION: The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.
Subject(s)
Amino Acids/urine , Collagen Type II/urine , Kashin-Beck Disease/diagnosis , Kashin-Beck Disease/urine , Peptide Fragments/urine , Adult , Aged , Biomarkers/urine , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
When screening for Kashin-Beck disease (KBD) in children, hand X-ray examination is the most important measure. However, there is high rate of misdiagnosis because of confusing X-ray signs. We studied the characteristics of positive and confusing hand X-ray signs. Clinical and radiological examinations were conducted in all 7- to 12-year-olds in selected villages from some KBD and non-KBD areas. We analysed the radiological and epidemiological characteristics of the X-ray signs of KBD and the confusing signs. Images from 3,193 children were valid. No cases of KBD were found. Seventeen children (0.53%) had X-ray signs positive for KBD. The confusing X-ray signs included closure reaction of metaphysis-epiphysis (CRME, 14.28%), thumb variation (0.22%), little finger variation (8.89%), the second metacarpal-phalangeal variation (0.13%) and cystic change (3.85%). The onset of CRME in children occurred earlier in girls (9) than in boys (10). The onset occurred earlier in KBD areas (9) than in non-KBD areas (10). The onset occurred earlier in Han children (9) than in Tibetan children (11). In summary, KBD was effectively controlled in all investigated KBD endemic villages, and the age range should be adjusted to 7- to 11-year-olds in Han children to reduce the misdiagnosis rates in KBD surveillance.
Subject(s)
Fingers/diagnostic imaging , Kashin-Beck Disease/diagnostic imaging , Radiography/methods , Thumb/diagnostic imaging , Child , China/epidemiology , Female , Fingers/physiopathology , Humans , Kashin-Beck Disease/diagnosis , Kashin-Beck Disease/physiopathology , Male , Thumb/physiopathology , X-RaysABSTRACT
Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents' hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.
Subject(s)
Hand/pathology , Hand/physiopathology , Kashin-Beck Disease/epidemiology , Knee Joint/pathology , Osteoarthritis/epidemiology , Endemic Diseases , Humans , Surveys and QuestionnairesABSTRACT
BACKGROUND: Kashin-Beck disease (KBD) is an endemic, chronic, degenerative osteoarthropathy. KBD is usually diagnosed by using X-ray image and clinical symptoms, lacking of serological biomarkers. The serum level of PIICP, PIIANP, and PIIBNP can specifically reflect the damage of the cartilage. So, in this study, the serum levels of PIICP, PIIANP, and PIIBNP were detected in order to determine whether they can be used as potential biomarkers for the diagnosis of KBD. METHOD: Using a status survey, the survey sites were selected in the KBD historical endemic areas and non-endemic areas in Jilin and Heilongjiang provinces. All local residents have undergone clinical examination, X-ray examination of the hands and knees, and questionnaire survey. A total of 554 people were surveyed, and 184 residents who are eligible for inclusion criteria were selected as our subjects. Fifty-six cases were diagnosed as KBD and 63 individuals were included as internal control and 65 subjects were included as external control. And blood samples of surveyed subjects were collected, and the serum was separated to detect the levels of PIICP, PIIANP, and PIIBNP by ELISA. Statistical analysis was performed using the SPSS software. RESULTS: There were no statistically significant differences in age and sex among the three groups. The Kruskal-Wallis H test showed that the serum levels of PIICP, PIIANP, and PIIBNP were significantly different among the three groups. Multiple comparisons using Dunnett's T3 test revealed that serum levels of PIICP, PIIANP, and PIIBNP were significantly lower in KBD patients than in internal and external control. However, there was no significant difference between the internal and external control. CONCLUSIONS: The results preliminarily indicated that the levels of PIICP, PIIANP, and PIIBNP in serum could reflect the abnormal synthesis of type II collagen in KBD patients and suggested that these indicators might be used as potential biomarkers for the diagnosis of KBD.