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1.
Front Hum Neurosci ; 16: 964550, 2022.
Article En | MEDLINE | ID: mdl-36405086

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases. Materials and methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018. Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time. Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.

2.
Front Plant Sci ; 13: 872422, 2022.
Article En | MEDLINE | ID: mdl-35677246

Field and pot experiments were conducted to explore the response mechanism of endogenous hormones of potential storage root to phosphorus and its relationship with yield and appearance quality of sweetpotato using five different rates of phosphorus addition. Application of adequate amounts of phosphorus (P2 treatment, 112 kg of P2O5 ha-1 in field experiment or 0.04 g of P2O5 kg-1 in pot experiment) improved the yield and the appearance quality of sweetpotato when compared to the control treatment. This observation can be attributed to the fact that P2 treatment significantly increased the expression of Ibkn1 and APRT genes and the concentration of ZR from 20 to 40 days after planting, but the results were the opposite at 10 days after planting. In addition, an increase in the expression of SRD1, NIT4, IbMADS1, and OPR3 and the concentrations of IAA and JA from day 10 to day 40 after planting were observed. Furthermore, the expression of GA3oX4 and the concentration of GA3 decreased significantly from 20 to 30 days of planting and significantly increased after 40 days of planting. Moreover, a significant decrease in the expression of AAO and concentration of ABA was observed from 10 to 30 days after planting, and a significant increase was observed after 40 days of planting. The results show that P2 treatment promoted root development, particularly significantly increased the number of roots and potential storage roots. P2 treatment significantly increased the diameter, weight, and number of storage roots at 40 days after planting. Finally, proper phosphorus application (112 kg of P2O5 ha-1) increased the yield (enhanced from 18.99 to 25.93%) by increasing the number of storage roots per plant and improving the appearance quality by increasing the length/diameter ratio and uniformity of storage root weight.

3.
Chin J Nat Med ; 20(4): 282-289, 2022 Apr.
Article En | MEDLINE | ID: mdl-35487598

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 µmol·L-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.


Mitochondrial Membrane Transport Proteins , Mitochondrial Permeability Transition Pore , Animals , Male , Mice , Rats , Atractyloside/pharmacology , Peptidyl-Prolyl Isomerase F , Mitochondrial Membrane Transport Proteins/genetics , Mitochondrial Membrane Transport Proteins/metabolism , RNA, Messenger
4.
Hepatology ; 76(3): 660-675, 2022 09.
Article En | MEDLINE | ID: mdl-34940991

BACKGROUND AND AIMS: No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof-of-concept strategy by combining the regulation of leukocyte cell-derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. APPROACH AND RESULTS: The CCl4 -induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno-associated viral vector serotype 9 (AAV9)-LECT2-short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9-LECT2-shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. CONCLUSIONS: Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9-LECT2-shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.


Liver Cirrhosis , Vascular Endothelial Growth Factor A , Animals , Bevacizumab/adverse effects , Disease Models, Animal , Liver/pathology , Liver Cirrhosis/metabolism , Mice , RNA, Small Interfering/therapeutic use , Vascular Endothelial Growth Factor A/metabolism
5.
Iran J Pharm Res ; 20(2): 144-155, 2021.
Article En | MEDLINE | ID: mdl-34567152

In order to find new drugs with potent antiproliferative effect, a series of novel barbituric acid derivatives containing azoles at the C-5 position were designed, synthesized, and evaluated for antiproliferative activity against three human cancer cell lines (BEL-7402, MCF-7, and HCT-116) using MTT assay. Several of the synthesized compounds exhibited potent antiproliferative effects. The most promising compound was 5-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl) methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (3s), which showed considerably high antiproliferative activity in the BEL-7402 cell line, with a half-maximal inhibitory concentration of 4.02 µM and 20.45-fold higher selectivity for BEL-7402 cells than for normal L02 cells. The apoptosis experiment showed that compound 3s induced apoptosis and cell necrosis in a concentration-dependent manner and exert its anti-proliferative activity. Therefore, compound 3s exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil.

6.
Front Oncol ; 11: 662444, 2021.
Article En | MEDLINE | ID: mdl-34195074

Species-specific lncRNAs significantly determine species-specific functions through various ways, such as epigenetic regulation. However, there has been no study focusing on the role of species-specific lncRNAs in other species yet. Here, we found that siRNAs targeting mouse-specific lncRNA AA388235 could significantly induce death of human tumor cells, although it has no effect on mouse tumor cells and normal human cells. The mechanism studies showed that these siRNAs could activate the response of human tumor cells to exogenous nucleic acids, induce pyroptosis and apoptosis in the presence of GSDME, but induce apoptosis in the absence of GSDME. They also significantly inhibited the growth of human tumor cells in vivo. 17 siRNAs were designed for seven more mouse-specific lncRNAs selected randomly, among which 12 siRNAs targeting five lncRNAs induced death in human tumor cell. Our study not only demonstrates that the siRNAs designed for knocking down mouse-specific lncRNA AA388235 can be potential tumor therapeutic drugs, but also suggests that non-human species-specific lncRNAs are a huge potential library that can be used to design siRNAs for tumor treatment. Large-scale screening based on this is promising.

7.
Transl Pediatr ; 10(12): 3248-3260, 2021 Dec.
Article En | MEDLINE | ID: mdl-35070839

BACKGROUND: If acute diarrhea in children is not treated promptly and effectively, it can lead to severe dehydration and serious sequelae. Due to the imbalance of intestinal bacteria in children with acute diarrhea, the supplementation with probiotics is important, which can improve the intestinal microenvironment, promote immunity, and enhance resistance. This meta-analysis provides further evidence and discussion of the therapeutic effect of probiotics on acute diarrhea in children. METHODS: MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched by rapid matching. The input keywords were as follows: (probiotics/synbiotics) and (child/children) and (acute diarrhea/acute gastroenteritis). Articles reporting on randomized controlled trials (RCTs) of probiotics in treating acute diarrhea in children were retrieved. The studies were published from 2010 to 2020. After screening and quality evaluation, Stata 16.0 software was used for the analysis. RESULTS: Twelve articles with 744 patients were included in the study, and the overall quality of the articles was excellent. Meta-analysis showed that the duration of diarrhea in the probiotics group was shorter than that in the control group [standard mean difference (SMD) =-0.74, 95% CI: -1.11 to -0.37, Z=-3.935, P=0.000], the 2-day treatment efficacy for diarrhea in the probiotics group was greater than that in the control group [odds ratio (OR) =2.12, 95% CI: 1.47-3.05, Z=3.998, P=0.000], and the length of hospital stay in the probiotics group was shorter than that of the control group (SMD =-0.60, 95% CI: -0.74 to -0.47, Z=-8.781, P=0.000). In the subgroup analysis, combined probiotics shortened the duration of diarrhea compared with single probiotic use, and Lactobacillus reuteri and Saccharomyces boulardii had a better therapeutic effect than Lactobacillus rhamnosus or Lactobacillus acidophilus. DISCUSSION: In the treatment of acute diarrhea in children, the addition of probiotics can shorten the duration of diarrhea, increase treatment efficacy after 2 days of treatment, and shorten the length of hospital stay. However, because of possible publication bias in the current study, further high-quality RCT studies in clinical settings are needed to verify the current results and continue the exploration of this topic.

8.
Animal Model Exp Med ; 4(4): 351-358, 2021 12.
Article En | MEDLINE | ID: mdl-34977486

Background: Oligoasthenospermia is one of the main causes of male infertility. Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models, which disregards the adhesion and migration between spermatogenic cells and Sertoli cells. TAp73 is a critical regulator of the adhesin of germ cell; thus, we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression. Methods: Mice in the Pifithrin-α group were injected intraperitoneally with 2.5 mg/kg Pifithrin-α (TAp73 inhibitor) daily for 30 consecutive days. Reproductive hormone levels and epididymal sperm quality, as well as the network morphology of Sertoli cells were tested. Results: Sperm density, motility, and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-α group compared with the normal control group. No significant distinction was observed in the relative mRNA and protein expression of ZO-1. Furthermore, the tight junctions (TJs) and apical ectoplasmic specialization (ES) were destroyed in the Pifithrin-α group. Conclusion: The above results indicate that we successfully established a new oligoasthenospermia mouse model. This study provides a foundation for further exploration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.


Oligospermia , Spermatogenesis , Animals , Epididymis , Male , Mice , Oligospermia/genetics , Sertoli Cells , Spermatogenesis/genetics , Spermatozoa
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1326-1331, 2020 Aug.
Article Zh | MEDLINE | ID: mdl-32798421

OBJECTIVE: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes. METHODS: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation. RESULTS: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03). CONCLUSION: Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.


Thrombocythemia, Essential , Bone Marrow , Calreticulin/genetics , China , Humans , Janus Kinase 2/genetics , Male , Mutation , Receptors, Thrombopoietin/genetics
10.
Molecules ; 26(1)2020 Dec 29.
Article En | MEDLINE | ID: mdl-33383694

Four complexes, [Cu4L2(OCH3)2(CH3OH)2]·2H2O (1), [Zn2L2Cl4]·2H2O·2CH3OH (2), [Hg2L2Br4]·4CH3OH (3), and {[CdL2Cl2]·4H2O·4CH3OH}n (4), have been synthesized and characterized from a bis(pyridylhydrazone) ligand (L) with copper(II), zinc(II), mercury(II) or cadmium(II), respectively. Complex 1 exists as a centrosymmetric tetranuclear dimer with L as deprotonated tridentate ligand. Complexes 2 and 3 exist as centrosymmetric metallamacrocycles with L as bidentate ligand. Complex 4 exists as a 1D looped-chain coordination polymer. The thermal stabilities and vapor adsorption properties of the four complexes were investigated as well.


Cadmium/chemistry , Coordination Complexes/chemistry , Copper/chemistry , Hydrazones/chemistry , Mercury/chemistry , Zinc/chemistry , 2,2'-Dipyridyl/chemical synthesis , 2,2'-Dipyridyl/chemistry , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , Hydrazones/chemical synthesis , Ligands , Models, Molecular
11.
AMB Express ; 9(1): 153, 2019 Sep 24.
Article En | MEDLINE | ID: mdl-31552501

Fermentation of chemicals from lignocellulose hydrolysate is an effective way to alleviate environmental and energy problems. However, fermentation inhibitors in hydrolysate and weak inhibitor tolerance of microorganisms limit its development. In this study, atmospheric and room temperature plasma mutation technology was utilized to generate mutant strains of Enterobacter cloacae and screen for mutants with high inhibitor tolerance to acid hydrolysate of corncobs. A highly inhibitor-tolerant strain, Enterobacter cloacae M22, was obtained after fermentation with non-detoxified hydrolysate, and this strain produced 24.32 g/L 2,3-butanediol and 14.93 g/L organic acids. Compared with that of the wild-type strain, inhibitor tolerance was enhanced twofold with M22, resulting in improvement of 2,3-butanediol and organic acid production by 114% and 90%, respectively. This work presents an efficient method to screen for highly inhibitor-tolerant strains and evidence of a novel strain that can produce 2,3-butanediol and organic acids using non-detoxified acid hydrolysate of corncobs.

12.
Cell ; 178(6): 1478-1492.e20, 2019 09 05.
Article En | MEDLINE | ID: mdl-31474362

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.


Endothelial Cells/metabolism , Hepatocytes/metabolism , Intercellular Signaling Peptides and Proteins/physiology , Liver Cirrhosis/metabolism , Liver/metabolism , Receptors, TIE/metabolism , Animals , Biomarkers/metabolism , Capillaries/metabolism , Endothelial Cells/cytology , Endothelial Cells/pathology , HEK293 Cells , Hepatocytes/cytology , Hepatocytes/pathology , Humans , Intercellular Signaling Peptides and Proteins/blood , Liver/blood supply , Liver/pathology , Liver Cirrhosis/diagnosis , Mice, Inbred C57BL
13.
Chin Med Sci J ; 34(1): 18-23, 2019 Mar 30.
Article En | MEDLINE | ID: mdl-30961776

Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging (T2WI) with fat saturation and enhanced T1 weighted imaging (T1WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2WI images. The normal optic nerve (NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic (ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement (ONwEN), affected optic nerve without enhancement (ONwoEN), contralateral normal appearing optic nerve (NAON) and NON.Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN (both P=0.000), ONwEN vs. NON (both P=0.000) and NAON vs. NON (both P<0.05). ROC analysis demonstrated that the area under the curve (AUC) of histogram texture Energy were 0.758, 0.795 and 0.701 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON, AUC of Entropy were 0.758, 0.795 and 0.707 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON.Conclusions The altered MRI histogram texture Energy and Entropy could be considered as a surrogate for MRI enhancement to evaluate the involved optic nerve and normal-appearing optic nerve in optic neuritis.


Magnetic Resonance Imaging , Optic Nerve/diagnostic imaging , Optic Neuritis/diagnostic imaging , Adolescent , Adult , Humans , Middle Aged
14.
Brain Imaging Behav ; 12(5): 1346-1354, 2018 Oct.
Article En | MEDLINE | ID: mdl-29234958

The basal ganglia (BG) are composed of several nuclei involved in neural processing associated with integration of sensory and motor information. Recent neuroimaging studies implicated its key role in control of voluntary motor function. As the sensorimotor abnormality is common among the end-stage renal disease (ESRD) population, in the current study, we aimed to investigate the abnormal structure and functional connectivity patterns of BG in ESRD patients. Twenty-nine ESRD and twenty-nine age and gender-matched healthy controls (HC) were enrolled to compare the volume of the subsets in the BG (e.g., caudate nucleus, putamen and globus pallidus) by using the VBM analysis; resting-state functional connectivity was analyzed by a seed-based method. Compared with the HC group, ESRD patients had a smaller volume in the right putamen. Taking the right putamen as a seed region, we further found reduced functional connectivity in patients mainly between the putamen and supplementary motor area (SMA), insula, posterior mid-cingulate gyrus, and primary motor cortex. In ESRD group, the severity score of restless legs syndrome was negatively correlated with putamen-SMA functional connectivity, while the hemoglobin level was positively correlated with functional connectivity degree between the putamen and SMA. Our results revealed an abnormal volume of the putamen and its decreased functional connectivity patterns during resting state in ESRD with sensorimotor abnormalities. These preliminary results indicated that the decreased functional connectivity in putamen-SMA was associated with sensorimotor abnormalities, and anemia was correlated with this abnormal functional pattern in ESRD patients.


Kidney Failure, Chronic/diagnostic imaging , Kidney Failure, Chronic/physiopathology , Motor Cortex/diagnostic imaging , Motor Cortex/physiopathology , Putamen/diagnostic imaging , Putamen/physiopathology , Adult , Brain Mapping , Female , Gray Matter/diagnostic imaging , Gray Matter/physiopathology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Prospective Studies , Rest
15.
Nat Commun ; 8(1): 1175, 2017 10 27.
Article En | MEDLINE | ID: mdl-29079780

Induction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here, we show that HGF/Rspo1 induce liver stem cells and rescue liver dysfunction. Carbon tetrachloride treatment promotes both fibrosis and Lgr5+ liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis. Injection of HGF in combination with Rspo1 increases the number of Lgr5+ liver stem cells and improves liver function by attenuating fibrosis. We observe Lgr5+ liver stem cells in human liver fibrosis tissues, and once they are isolated, these cells are able to form organoids, and treatment with HGF/Rspo1 promotes their expansion. We suggest that Lgr5+ liver stem cells represent a valuable target for liver damage treatment, and that HGF/Rspo1 can be used to promote liver stem cell expansion.


Liver Cirrhosis/metabolism , Receptors, G-Protein-Coupled/metabolism , Thrombospondins/metabolism , Adult , Animals , Biopsy , Carbon Tetrachloride , Cell Proliferation , Female , Fibrosis/metabolism , Gene Deletion , Glycogen/chemistry , Green Fluorescent Proteins/metabolism , Hepatocytes/cytology , Humans , Liver/metabolism , Liver/physiopathology , Male , Mice , Mice, Inbred C57BL , Stem Cells/cytology , Young Adult
16.
J Am Coll Cardiol ; 70(16): 2006-2019, 2017 Oct 17.
Article En | MEDLINE | ID: mdl-29025558

BACKGROUND: Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes. OBJECTIVES: This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV. METHODS: The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study. ApoA-IV was precipitated from ultracentrifugally isolated high-density lipoprotein, and its glycation level was determined based on Western blotting densitometry (relative intensity of apoA-IV glycation). ApoA-IV NƐ-(carboxylmethyl) lysine (CML) modification sites were identified by mass spectrometry in 37 control subjects, 63 patients in Group I, and 138 patients in Group II. Saline or glycated apoA-IV (g-apoA-IV) generated by glyoxal culture was injected into apoE-/- mice to evaluate atherogenesis, and was also used for the cell experiments. RESULTS: The relative intensity and the abundance of apoA-IV glycation were associated with the presence and severity of CAD in patients with T2DM (all p < 0.05). The experiments showed that g-apoA-IV induced proinflammatory reactions in vitro and promoted atherogenesis in apoE-/- mice through the nuclear receptor NR4A3. G-apoA-IV with mutations (K-A) at high-frequency glycation sites exhibited more weakened proinflammatory and atherogenic effects than did g-apoA-IV both in vitro and in vivo. CONCLUSIONS: ApoA-IV glycation is associated with CAD severity in patients with T2DM, and g-apoA-IV induces atherogenesis through NR4A3 in apoE-/- mice.


Apolipoproteins A/metabolism , Atherosclerosis/metabolism , Coronary Artery Disease/metabolism , Diabetes Mellitus, Type 2/metabolism , Aged , Animals , Apolipoproteins A/isolation & purification , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Biomarkers/metabolism , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Diabetes Mellitus, Type 2/diagnostic imaging , Diabetes Mellitus, Type 2/epidemiology , Female , Glycosylation , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged
17.
Am J Cardiol ; 118(11): 1674-1679, 2016 Dec 01.
Article En | MEDLINE | ID: mdl-27666175

Although high-density lipoprotein (HDL) can exhibit anti-inflammatory properties, these potent activities can become deficient and even transform into proinflammatory effects under various pathophysiological states. We investigated the effect of diabetic HDL on the inflammatory response in human monocytes and its relation to the existence of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM). HDL was isolated from DM patients with (n = 61) or without (n = 31) CAD (diameter stenosis ≥50%) and healthy controls (n = 40). Human peripheral blood mononuclear cells were incubated with HDL and the proinflammatory ability of HDL was determined by tumor necrosis factor-α (TNF-α) secretion in peripheral blood mononuclear cells. Secretion of TNF-α in human monocytes in response to diabetic HDL was significantly increased compared with that of the control HDL. Of note, HDL from DM patients with CAD stimulated the release of TNF-α in monocytes to a greater extent than that of HDL from those without CAD. Multiple linear regression analysis showed that the proinflammatory ability of HDL was independently associated with diabetes duration, hemoglobin A1c, serum levels of high-sensitivity C-reactive protein (hs-CRP) and reduced glomerular filtration rate (GFR). Furthermore, the proinflammatory ability of HDL was a significant predictor for the presence of CAD in patients with DM.


Coronary Artery Disease/complications , Diabetes Mellitus, Type 2/blood , Lipoproteins, HDL/blood , Aged , Biomarkers/blood , Coronary Angiography , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Diabetes Mellitus, Type 2/complications , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Monocytes/metabolism , Retrospective Studies , Severity of Illness Index , Time Factors
18.
Ying Yong Sheng Tai Xue Bao ; 26(4): 1016-22, 2015 Apr.
Article Zh | MEDLINE | ID: mdl-26259441

This paper developed a new interpretation symbol system for grading and classifying saline-alkali land, using Huanghua, a cosatal city in Hebei Province as a case. The system was developed by inverting remote sensing images from 1992 to 2011 based on site investigation, plant cover characteristics and features of remote sensing images. Combining this interpretation symbol system with supervising classification method, the information on arable land was obtained for the coastal saline-alkali ecosystem of Huanghua City, and the saline-alkali land area, changes in intensity of salinity-alkalinity and spatial distribution from 1992 to 2011 were analyzed. The results showed that salinization of arable land in Huanghua City alleviated from 1992 to 2011. The severely and moderately saline-alkali land area decreased in 2011 compared with 1992, while the non/slightly saline land area increased. The moderately saline-alkali land in southeast transformed to non/slightly saline-alkaline, while the severely saline-alkali land in west of the city far from the coastal zone became moderately saline-alkaline. The center of gravity (CG) of severely and non/slightly saline-alkali land moved closer the coastline, while that of the moderately saline-alkali land moved from southwest coastal line to northwest. Factors influencing changes in arable land within the saline-alkali ecosystem of Huanghua City were climate, hydrology and human activities.


Ecosystem , Remote Sensing Technology , Salinity , Agriculture , Alkalies , China , Cities , Climate , Hydrology , Plants
19.
J Crit Care ; 30(3): 654.e9-14, 2015 Jun.
Article En | MEDLINE | ID: mdl-25575850

BACKGROUNDS: Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. AIMS: The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. PATIENTS AND METHODS: A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. RESULTS: The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05) were significantly higher in the deceased group than those in the survived group. The predicting mortality of APACHE-II score alone was low but largely improved, when it was combined with both NT-proBNP and cTnI (P < .05). CONCLUSION: The alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in elderly patients with severe sepsis or septic shock. N-terminal pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI.


Intensive Care Units , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Shock, Septic/blood , Troponin I/blood , APACHE , Aged , Aged, 80 and over , Biomarkers , C-Reactive Protein/metabolism , Cohort Studies , Female , Humans , Male , Prognosis , Retrospective Studies , Sepsis/blood , Sepsis/mortality , Shock, Septic/mortality
20.
Colloids Surf B Biointerfaces ; 107: 11-8, 2013 Jul 01.
Article En | MEDLINE | ID: mdl-23466537

The present study investigated the biosorption capacity of live and dead cells of Bacillus cereus RC-1 for Cd(II). The biosorption characteristics were investigated as a function of initial pH, contact time, and initial cadmium concentration. Equilibrium biosorption was modeled using Langmuir, Freundlich and Redlich-Peterson isotherm equations. It was found that the maximum biosorption capacities calculated from Langmuir isotherm were 31.95 mg/g and 24.01 mg/g for dead cells and live cells, respectively. The kinetics of the biosorption was better described by pseudo-second order kinetic model. Desorption efficiency of biosorbents was investigated at various pH values. These results indicated that dead cells have higher Cd(II) biosorption capacity than live cells. Furthermore, zeta potential, transmission electron microscopy (TEM), scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX), and Fourier transform infrared spectroscopy (FTIR) studies were carried out to understand the differences in the Cd(II) biosorption behavior for the both biosorbents. The bioaccumulation of Cd(II) by B. cereus RC-1 was found to depend largely on extracellular biosorption rather than intracellular accumulation. Based on the above studies, dead biomass appears to be a more efficient biosorbent for the removal of Cd(II) from aqueous solution.


Bacillus cereus/cytology , Bacillus cereus/isolation & purification , Cadmium/isolation & purification , Microbial Viability , Soil Microbiology , Soil Pollutants/isolation & purification , Adsorption , Bacillus cereus/metabolism , Bacillus cereus/ultrastructure , Batch Cell Culture Techniques , Biodegradation, Environmental , Hydrogen-Ion Concentration , Ions , Kinetics , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Static Electricity , Temperature , Time Factors
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