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1.
Clin Res Hepatol Gastroenterol ; 48(3): 102290, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38311060

ABSTRACT

The primary treatment for early esophageal cancer and precancerous lesions is endoscopic submucosal dissection (ESD). However, this approach leads to a high incidence of postoperative esophageal stenosis, which can significantly impact a patient's quality of life. While various methods are available to prevent post-ESD esophageal stenosis, their effectiveness varies. Therefore, this study aims to provide an overview of the currently employed methods for preventing post-ESD esophageal stenosis in clinical practice in view of assisting clinical practitioners.


Subject(s)
Endoscopic Mucosal Resection , Esophageal Neoplasms , Esophageal Stenosis , Humans , Esophageal Stenosis/etiology , Esophageal Stenosis/prevention & control , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Quality of Life , Esophageal Neoplasms/pathology , Postoperative Complications/prevention & control , Postoperative Complications/etiology
2.
Acta Pharm Sin B ; 13(1): 271-283, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36815054

ABSTRACT

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.

3.
Nat Biomed Eng ; 6(2): 168-180, 2022 02.
Article in English | MEDLINE | ID: mdl-34312508

ABSTRACT

The pathology of familial Alzheimer's disease, which is caused by dominant mutations in the gene that encodes amyloid-beta precursor protein (APP) and in those that encode presenilin 1 and presenilin 2, is characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles in multiple brain regions. Here we show that the brain-wide selective disruption of a mutated APP allele in transgenic mouse models carrying the human APP Swedish mutation alleviates amyloid-beta-associated pathologies for at least six months after a single intrahippocampal administration of an adeno-associated virus that encodes both Cas9 and a single-guide RNA that targets the mutation. We also show that the deposition of amyloid-beta, as well as microgliosis, neurite dystrophy and the impairment of cognitive performance, can all be ameliorated when the CRISPR-Cas9 construct is delivered intravenously via a modified adeno-associated virus that can cross the blood-brain barrier. Brain-wide disease-modifying genome editing could represent a viable strategy for the treatment of familial Alzheimer's disease and other monogenic diseases that affect multiple brain regions.


Subject(s)
Alzheimer Disease , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Brain/metabolism , CRISPR-Cas Systems , Mice , Mice, Transgenic
4.
Nat Neurosci ; 25(1): 106-115, 2022 01.
Article in English | MEDLINE | ID: mdl-34887588

ABSTRACT

Genetic intervention is increasingly being explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies rely upon expressing a transgene in affected cells while minimizing off-target expression. Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and sequential engineering of AAV-PHP.eB between the surface-exposed AA452 and AA460 of VP3. From this selection, we identified capsid variants that were enriched in the brain and targeted away from the liver in C57BL/6J mice. This tropism extends to marmoset (Callithrix jacchus), enabling robust, non-invasive gene delivery to the marmoset brain after intravenous administration. Notably, the capsids identified result in distinct transgene expression profiles within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates enables new avenues for basic research and therapeutic possibilities unattainable with naturally occurring serotypes.


Subject(s)
Capsid , Dependovirus , Administration, Intravenous , Animals , Brain/metabolism , Callithrix/genetics , Dependovirus/genetics , Genetic Vectors , Liver , Mice , Mice, Inbred C57BL , Transduction, Genetic , Transgenes
5.
J Anim Physiol Anim Nutr (Berl) ; 106(6): 1258-1267, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34927293

ABSTRACT

Experiment was conducted to study the effects of Mulberry Leaf (ML) powder on reproductive performance, serum and milk amino acid composition in sows. Fifty sows (D 85 at gestation) with parity 3 or 4 were randomly divided into 5 groups: C, M100, M200, M300 and M400, receiving 0, 100, 200, 300 and 400 g ML powder per sow per day. Blood and milk of sows at Days 1 and 21 of lactation were collected. Results showed that average daily feed intake (ADFI) during lactation was higher in groups supplemented ML compared with control group (p < 0.01). Litter weight gain during lactation was higher in M400 than in groups M200 and C (p < 0.05), with no significant difference compared with M100 and M300. Serum glucose concentration in groups M400 and M300 was higher than those in the other groups (p < 0.01). Serum HDL-C concentration in group M400 was significantly greater than those in groups M100 and M200 (p < 0.05), with no significant difference between group M400 and groups M300, control. Milk amino acid concentrations such as isoleucine, leucine, lysine and valine were all lower in group M400 than in control (p < 0.01). Serum methionine (Met) concentration was higher in M300 than in other groups (p < 0.01). Milk Met concentration in group C was higher than those of the sows in the group M400, with no significant difference compared with groups M100, M200 and M300 (p < 0.05). Serum Lys and Met concentrations were lower in M400 than in control group (p < 0.05). In summary, our results have revealed the ML supplementation at a high dose such as 300 g/day during later gestation and lactation showed benefit in regulating lipid and amino acid metabolism in sows and then improved growth performance of their offspring.


Subject(s)
Milk , Morus , Swine , Animals , Female , Pregnancy , Milk/chemistry , Lactation/physiology , Amino Acids/metabolism , Powders/pharmacology , Litter Size , Diet/veterinary , Lysine/pharmacology , Plant Leaves/metabolism , Animal Feed/analysis
6.
Medicine (Baltimore) ; 101(51): e31850, 2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36595876

ABSTRACT

BACKGROUND: Assess the efficiency and cost-effectiveness of infliximab, cyclosporine and tacrolimus for the treatment of ulcerative colitis (UC). METHODS: A literature search identified studies that investigated infliximab, cyclosporine or tacrolimus compared with placebo in UC patients. Short-term, long-term remission rates and response rates were employed to assess efficacy. Odds ratios with 95% confidence intervals were analyzed. A Markov model was constructed to simulate the progression in a cohort of patients with UC, with an over 10 years of time horizon, with a discount rate of 3%, and established threshold of €30,000/quality-adjusted life-year (QALY) or ¥82442/QALY. RESULTS: Results of network meta-analysis showed that the order was cyclosporine, tacrolimus, infliximab and placebo from high rate to low with regard to short-term clinical response. The comparison between infliximab versus cyclosporine achieved an incremental cost effectiveness ratio (ICER) of €184435/QALY and ¥531607/QALY, with a 0.34893 QALYs difference of efficacy, and an incremental cost of €64355 and ¥185494. Tacrolimus versus cyclosporine reached an ICER of €44236/QALY and ¥57494/QALY, with a difference of 0.40963 QALYs in efficacy, and a raising cost to €18120 and ¥23551. The probabilistic sensitivity analysis shows that cyclosporine would be cost-effective in the 75.8% of the simulations, tacrolimus in the 24.2%, and infliximab for the 0%. CONCLUSION: Infliximab, cyclosporine and tacrolimus as salvage therapies are efficacious. For long-term of clinical remission, the order of pharmacological agents was tacrolimus, infliximab and cyclosporine from high efficacy to low while no significant difference is seen. In cost-effectiveness analysis, the cyclosporine versus infliximab or tacrolimus is expected to be at best.


Subject(s)
Colitis, Ulcerative , Humans , Infliximab/therapeutic use , Colitis, Ulcerative/drug therapy , Cyclosporine/therapeutic use , Tacrolimus/therapeutic use , Cost-Effectiveness Analysis , Network Meta-Analysis , Cost-Benefit Analysis , Quality-Adjusted Life Years , Treatment Outcome
7.
Brain Behav ; 11(11): e2359, 2021 11.
Article in English | MEDLINE | ID: mdl-34551452

ABSTRACT

BACKGROUND: Freezing of gait (FOG) is a disabling paroxysmal gait disorder that prevents starting or resuming walking, which seriously negatively affects patients' quality of life (QOL). The diagnosis and treatment of FOG remain a huge medical challenge. The purpose of this study was to explore the clinical characteristics and related factors of FOG in patients with Parkinson's disease (PD). METHODS: The motor and nonmotor symptoms of a total number of 77 PD patients were evaluated. Patients with or without FOG were defined as a score ≥1 in the new freezing of gait questionnaire (NFOG-Q). A comparative study between patients with and without FOG was conducted. RESULTS: In this investigation, the prevalence of FOG was 48%. The patients with FOG had longer disease duration, higher Hoehn-Yahr stage (H-Y stage), higher dose of dopaminergic agents, and higher nonmotor and motor symptom scores. A significant positive correlation was found between the NFOG-Q score and the H-Y stage, PIGD subscore, PDQ-39, and the attention/memory in the nonmotor symptoms assessment scale (NMSS) subitem (r > 0.5, p < .05). The binary logistic regression analysis showed that the higher H-Y stage, higher rigidity subscore and Unified Parkinson's Disease Rating Scale II (UPDRS II) score, and UPDRS III score were significantly correlated with the occurrence of FOG (p < .05). In the analysis of the frequency of FOG, the prevalence of FOG in H-Y stage was higher in the middle and late stages, and the prevalence of FOG increased with the increase in PDQ-39 scores. CONCLUSION: The severity of FOG was significantly positively correlated with the H-Y stage, PIGD subscore, PDQ-39 score, and attention/memory score. Based on our findings, we conclude that the clinical characteristics of rigidity can be used as a potential predictor of FOG.


Subject(s)
Gait Disorders, Neurologic , Parkinson Disease , Gait , Gait Disorders, Neurologic/epidemiology , Gait Disorders, Neurologic/etiology , Humans , Parkinson Disease/complications , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Quality of Life , Severity of Illness Index
8.
Int J Biol Macromol ; 184: 109-117, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34119541

ABSTRACT

A self-strengthening coating with silver nanoparticles (Ag NPs) doped chitosan (CHI) and sodium alginate (SA) polyelectrolytes was constructed on the surface of polydopamine (PDA) coated Ti substrate by a layer-by-layer assembly method. The PDA coating exhibited an excellent bond with Ti substrate, and also can uniformly deposit Ag NPs via a mild method without introducing any exogenous reductant. The CHI coating was assembled through a spin-coating method for controlling Ag+ release. The SA was introduced to enhance the anticorrosion performance by forming calcium alginate (CA) in a corrosive medium. The corrosion protection was investigated with electrochemical impedance spectroscopy and polarization curves tests in fluorine-containing artificial saliva. During immersion, the charge-transfer resistance and the protection efficiency (ŋ) presented a continuous increase with the immersion time, demonstrating that this coating possessed a remarkable self-strengthening capability, and the compositions of the outermost film changed from SA to CA with the Ca2+ cations of the corrosive medium as a crosslinker by SEM and EDS analysis. Furthermore, the ŋ remained up to 96.8% after immersion of 30 days, and then the coating also displayed a distinct inhibition zone on S. mutans. These results prove this coating possesses an excellent anticorrosion performance and antibacterial property.


Subject(s)
Alginates/chemistry , Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Coated Materials, Biocompatible/chemistry , Titanium/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Cell Line , Corrosion , Indoles/chemistry , Materials Testing , Metal Nanoparticles , Mice , Polyelectrolytes/chemistry , Polymers/chemistry , Saliva, Artificial , Streptococcus mutans/drug effects , Surface Properties , Titanium/chemistry
9.
Mol Neurobiol ; 58(8): 3729-3744, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33821423

ABSTRACT

Specification of the progenitors' regional identity is a pivotal step during development of the cerebral cortex and basal ganglia. The molecular mechanisms underlying progenitor regionalization, however, are poorly understood. Here we showed that the transcription factor Vax1 was highly expressed in the developing subpallium. In its absence, the RNA-Seq analysis, in situ RNA hybridization, and immunofluorescence staining results showed that the cell proliferation was increased in the subpallium, but the neuronal differentiation was blocked. Moreover, the dLGE expands ventrally, and the vLGE, MGE, and septum get smaller. Finally, overexpressed VAX1 in the LGE progenitors strongly inhibits Gsx2 expression. Taken together, our findings show that Vax1 is crucial for subpallium regionalization by repressing Gsx2.


Subject(s)
Corpus Striatum/embryology , Corpus Striatum/metabolism , Globus Pallidus/embryology , Globus Pallidus/metabolism , Homeodomain Proteins/biosynthesis , Neuropeptides/biosynthesis , Animals , Corpus Striatum/cytology , Globus Pallidus/cytology , Homeodomain Proteins/antagonists & inhibitors , Homeodomain Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neural Stem Cells/metabolism , Neurogenesis/physiology , Neuropeptides/genetics
10.
Neurosci Bull ; 37(4): 440-460, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33606177

ABSTRACT

Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1+EGFR+ apical multipotent intermediate progenitors (MIPCs), which then differentiate into basal MIPCs that express ASCL1, EGFR, OLIG2, and MKI67. These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons. Finally, single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons. Taken together, this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.


Subject(s)
Neural Stem Cells , Neurogenesis , Animals , Cell Differentiation , Mice , Neuroglia , Oligodendroglia
11.
Commun Biol ; 4(1): 195, 2021 02 12.
Article in English | MEDLINE | ID: mdl-33580208

ABSTRACT

The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer's disease. However, there is currently no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. We first generate a Cas9 nickase variant with broader protospacer-adjacent motif specificity to expand the targetability of double-nicking-mediated genome editing. As a proof-of-concept study, we examine the gene dosage effects on an Alzheimer's disease patient-derived iPSC line that carries three copies of APP (amyloid precursor protein). This method enables the rapid and simultaneous generation of iPSC lines with monoallelic, biallelic, or triallelic knockout of APP. The cortical neurons generated from isogenically corrected iPSCs exhibit gene dosage-dependent correction of disease-associated phenotypes of amyloid-beta secretion and Tau hyperphosphorylation. Thus, the rapid generation of iPSCs with different gene dosages using our method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.


Subject(s)
CRISPR-Associated Protein 9/genetics , CRISPR-Cas Systems , Clustered Regularly Interspaced Short Palindromic Repeats , DNA Copy Number Variations , Gene Dosage , Gene Editing , Induced Pluripotent Stem Cells/metabolism , Neurons/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Apoptosis , CRISPR-Associated Protein 9/metabolism , Cell Line , Gene Expression Regulation , Humans , Induced Pluripotent Stem Cells/pathology , Neurogenesis , Neurons/pathology , Phosphorylation , Proof of Concept Study , tau Proteins/metabolism
12.
J Mol Neurosci ; 71(3): 583-595, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32901373

ABSTRACT

Spinal cord microcirculation plays an important role in maintaining the function of spinal cord neurons and other cells. Previous studies have largely focused on the ability of microtubule stabilization to inhibit the fibroblast migration and promote axon regeneration after spinal cord injury (SCI). However, the effect of microtubule stabilization treatment on microcirculation reconstruction after SCI remains unclear. By using immunofluorescence, we found that microtubule stabilization treatment improved microcirculation reconstruction via increasing the number of microvessels, pericytes, and the perfused microvessels after SCI. To clarify the underlying mechanisms, rat brain microvascular endothelial cells and pericytes were subjected to glucose oxygen deprivation. By using flow cytometry and western blotting, we found that microtubule stabilization treatment inhibited apoptosis and migration of endothelial cells and pericytes but promoted proliferation and survival of endothelial cells and pericytes through upregulated expression of vascular endothelial growth factor A (VEGFA), VEGF receptor 2, platelet-derived growth factor-B (PDGFB), PDGF receptor ß, and angiopoietin-1 after SCI. Taken together, this study provides evidence for the mechanisms underlying the promotion of microcirculation reconstruction after SCI by microtubule stabilization treatment. Importantly, this study suggests the potential of microtubule stabilization as a therapeutic target to reduce microcirculation dysfunction after SCI in the clinic.


Subject(s)
Epothilones/pharmacology , Microcirculation , Microtubules/metabolism , Spinal Cord Injuries/drug therapy , Tubulin Modulators/pharmacology , Animals , Apoptosis , Cell Hypoxia , Cell Movement , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Epothilones/therapeutic use , Female , Glucose/deficiency , Microtubules/drug effects , Pericytes/drug effects , Pericytes/metabolism , Platelet-Derived Growth Factor/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Platelet-Derived Growth Factor/metabolism , Receptors, Vascular Endothelial Growth Factor/metabolism , Spinal Cord/blood supply , Spinal Cord/metabolism , Tubulin Modulators/therapeutic use , Vascular Endothelial Growth Factor A/metabolism
13.
Neuromolecular Med ; 23(2): 327-334, 2021 06.
Article in English | MEDLINE | ID: mdl-33085068

ABSTRACT

Parkinson's disease (PD) is a common neurodegenerative disease in the middle-aged and elderly populations. The purpose of this study was to investigate the clinical value of lncRNA TUG1 in PD and its effect on the microglial inflammatory response. A total of 181 subjects were recruited for the study, including 97 patients with PD (male/female 50/47) and 84 healthy individuals (male/female 41/43). There was no significant difference for gender and age distribution between the groups. The expression of serum TUG1 was determined by qRT-PCR. The receiver operating curve (ROC) was applied for diagnostic value analysis. CCK-8 was used to detect the effect of TUG1 on the proliferation of BV2 cells. The motor coordination ability of mice was tested by the rotarod and pole tests. ELISA was used to detect serum pro-inflammatory factors. TUG1 was highly expressed in the serum of PD patients. Serum TUG1 can distinguish PD patients to form healthy controls with the AUC of 0.902. Serum TUG1 was positively correlated with the levels of UPDRS, IL-6, IL-1ß, and TNF-α in PD patients. Cell experiment results showed that the downregulation of TUG1 significantly inhibited cell proliferation and the release of TNF-α, IL-6, and IL-1ß. Besides, animal experiments suggested that the downregulation of TUG1 significantly improved the motor coordination ability of the PD mice and inhibited the expression of inflammatory factors. lncRNA TUG1 is a latent biomarker of PD patients. TUG1 downregulation may inhibit the inflammatory response in the progression of PD. These findings provide a possible target for the early diagnosis and therapeutic intervention of PD.


Subject(s)
Inflammation/genetics , Microglia/pathology , Parkinson Disease/genetics , RNA, Long Noncoding/genetics , Aged , Animals , Area Under Curve , Biomarkers , Cell Division , Cell Line , Cytokines/blood , Female , Humans , Inflammation/metabolism , Male , Mice , Mice, Inbred C57BL , Microglia/metabolism , Middle Aged , Parkinson Disease/blood , Parkinson Disease/pathology , Parkinsonian Disorders/genetics , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/pathology , RNA/genetics , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/blood , ROC Curve , Rotarod Performance Test , Sensitivity and Specificity , Severity of Illness Index , Transfection
14.
Fitoterapia ; 146: 104682, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32628985

ABSTRACT

Six new Diels-Alder type adducts, morusalisins A-F (1-6), were isolated from Morus alba cell cultures. The structures of 1-6 were determined by extensive spectroscopic data analysis, including HRESIMS, NMR, and ECD experiments. Furthermore, compounds 1-6 exhibited potent protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values ranging from 1.14 to 2.24 µM, making them promising as bioactive compounds for anti-diabetic drug discovery.


Subject(s)
Enzyme Inhibitors/pharmacology , Morus/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Cell Culture Techniques , Enzyme Inhibitors/isolation & purification , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology
15.
Mater Sci Eng C Mater Biol Appl ; 108: 110501, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31923942

ABSTRACT

An electrochemical aptasensor for the lipopolysaccharide (LPS) detection was constructed by using copper-based metal-organic framework (Cu-MOF) as a label and the LPS aptamer of specific single-stranded DNA as a probe. The carboxyl-functionalized polypyrrole nanowires (PPy NWs) were synthesized by electrochemical polymerization method, and the amino-terminated aptamer covalently coupling with the carboxyl group of the PPy NWs was immobilized onto the modified electrode. The aptamer can specifically combine with the target LPS molecules, and Cu-MOF was labeled by adsorption based on specific interactions of LPS carbohydrate portions with anionic groups. The fabrication processes of the aptasensor were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Differential pulse voltammetry (DPV) was used to measure electrochemical performance of the aptasensor, and the electrochemical signal can be directly measured by the electrochemical redox reaction of Cu(II)/Cu(I) existed in the Cu-MOF. The electrochemical aptasensor exhibited a high sensitivity toward LPS ranging from 1.0 pg/mL to 1.0 ng/mL with a detection limit of 0.29 pg/mL. Moreover, the developed sensor was found to have good selectivity, stability and regeneration properties, and the sensor also successfully detected LPS in real tap water samples.


Subject(s)
Copper/chemistry , Electrochemical Techniques/instrumentation , Lipopolysaccharides/analysis , Metal-Organic Frameworks/chemistry , Adsorption , Aptamers, Nucleotide/chemistry , Biosensing Techniques , Dielectric Spectroscopy , Electrodes , Limit of Detection , Microscopy, Electron, Scanning , Nanowires/chemistry , Oxidation-Reduction
16.
PeerJ ; 7: e7515, 2019.
Article in English | MEDLINE | ID: mdl-31534839

ABSTRACT

OBJECTIVE: This study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy. MATERIALS AND METHODS: Transcriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes. RESULTS: We found a significant correlation of an expression module with distant relapse-free survival (HR = 0.213, 95% CI [0.131-0.347], P = 4.80E-9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients. CONCLUSION: We used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

17.
Life Sci ; 231: 116536, 2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31176785

ABSTRACT

AIMS: TL1A was reported to contribute to the susceptibility to ulcerative colitis (UC). However, the molecular mechanisms of TL1A in UC development are poorly understood. We aimed to investigate the role of TL1A in colitis, and reveal the regulatory mechanism of TL1A in chronic colitis development. MAIN METHODS: Wild-type mice and transgenic mice with overexpressing TL1A in lymphocytes were used to construct chronic DSS colitis models. To investigate the molecular mechanism in vitro, CD4+ T cells were sorted from spleens and mesenteric lymph node cells to induce Th9 cells. Biopsy specimens from ulcerative colitis patients were collected for in vivo validation. KEY FINDINGS: The elevated TL1A expression in chronic DSS colitis models exacerbated intestinal inflammation. The differentiation of Th9 cells, IL-9 secretion and production of TGF-ß, IL-4 and PU.1 was significantly enhanced in transgenic mice with TL1A overexpression. In vitro results showed that TL1A enhanced the Th9 cells, IL-9 and PU.1 production, while TL1A antibodies inhibited their production. In human translational studies, patients with ulcerative colitis with elevated TL1A expression also exhibited more serious inflammation with higher levels of Th9 cells, IL-9 and PU.1 expression. SIGNIFICANCE: We presented a possible mechanism of TL1A in UC development that TL1A may promote the differentiation of Th9 cells and enhanced IL-9 secretion by up-regulating the expression of TGF-ß, IL-4 and PU.1, which provided a novel perspective to study the UC pathogenesis, and indicated that targeting of TL1A signal pathway may by a likely strategy for the treatment of chronic colitis.


Subject(s)
Colitis/immunology , Interleukin-9/immunology , T-Lymphocytes/immunology , Tumor Necrosis Factor Ligand Superfamily Member 15/immunology , Animals , Cell Differentiation/immunology , Colitis/chemically induced , Colitis/pathology , Cytokines/immunology , Cytokines/metabolism , Glutathione/metabolism , Interleukin-17/immunology , Interleukin-1beta/metabolism , Interleukin-9/metabolism , Intestinal Mucosa/immunology , Intestines/immunology , Intestines/pathology , Lymphocyte Activation , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Signal Transduction , T-Lymphocyte Subsets/immunology , Transforming Growth Factor beta/immunology , Tumor Necrosis Factor Ligand Superfamily Member 15/biosynthesis , Tumor Necrosis Factor-alpha/metabolism
18.
Neurodegener Dis ; 19(5-6): 204-210, 2019.
Article in English | MEDLINE | ID: mdl-32485710

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease characterized by intracellular α-synuclein (α-Syn) deposition. Alternation of the α-Syn expression level in plasma or erythrocytes may be used as a potential PD biomarker. However, no studies have compared their prognostic value directly with the same cohort. METHODS: The levels of α-Syn in plasma and erythrocytes, obtained from 45 PD patients and 45 control subjects, were measured with enzyme-linked immunosorbent assay. Then, correlation and receiver operating characteristic curve (ROC) analysis were performed to characterize the predictive power of erythrocytic and plasma α-Syn. RESULTS: Our results showed that α-Syn expression levels in both plasma and erythrocytes were significantly higher in PD patients than in control subjects (823.14 ± 257.79 vs. 297.10 ± 192.82 pg/mL, p < 0.0001 in plasma; 3,104.14 ± 143.03 vs. 2,944.82 ± 200.41 pg/mL, p < 0.001 in erythrocytes, respectively). The results of the ROC analysis suggested that plasma α-Syn exhibited better predictive power than erythrocytic α-Syn with a sensitivity of 80.0%, specificity of 97.7%, and a positive predictive value of 77.8%. The expression level of plasma α-Syn correlated well with the age of patients, H-Y stage, MoCA scale, and UPDRS motor scale. On the contrary, there was no correlation between erythrocytic α-Syn level and clinical parameters in this study. CONCLUSION: Our results suggest that plasma α-Syn could be a specific and sensitive potential diagnostic biomarker for PD.


Subject(s)
Erythrocytes/metabolism , Parkinson Disease/blood , alpha-Synuclein/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Severity of Illness Index
20.
Oncotarget ; 6(37): 39725-39, 2015 Nov 24.
Article in English | MEDLINE | ID: mdl-26498685

ABSTRACT

BACKGROUND: Cancer patients suffer from diverse symptoms, including depression, anxiety, pain, and fatigue and lower quality of life (QoL) during disease progression. This study aimed to evaluate the benefits of Traditional Chinese Medicine psycho-behavioral interventions (TCM PBIs) on improving QoL by meta-analysis. RESULTS: The six TCM PBIs analyzed were acupuncture, Chinese massage, Traditional Chinese Medicine five elements musical intervention (TCM FEMI), Traditional Chinese Medicine dietary supplement (TCM DS), Qigong and Tai Chi. Although both TCM PBIs and non-TCM PBIs reduced functional impairments in cancer patients and led to pain relief, depression remission, reduced time to flatulence following surgery and sleep improvement, TCM PBIs showed more beneficial effects as assessed by reducing both fatigue and gastrointestinal distress. In particular, acupuncture relieved fatigue, reduced diarrhea and decreased time to flatulence after surgery in cancer patients, while therapeutic Chinese massage reduced time to flatulence and time to peristaltic sound. METHODS: Electronic literature databases (PubMed, CNKI, VIP, and Wanfang) were searched for randomized, controlled trials conducted in China. The primary intervention was TCM PBIs. The main outcome was health-related QoL (HR QoL) post-treatment. We applied standard meta analytic techniques to analyze data from papers that reached acceptable criteria. CONCLUSION: These findings demonstrate the efficacy of TCM PBIs in improving QoL in cancer patients and establish that TCM PBIs represent beneficial adjunctive therapies for cancer patients.


Subject(s)
Behavior Therapy/methods , Medicine, Chinese Traditional/methods , Neoplasms/therapy , Psychotherapy/methods , Quality of Life , Acupuncture Therapy/methods , Clinical Trials as Topic , Diet Therapy/methods , Fatigue/therapy , Female , Gastrointestinal Diseases/therapy , Humans , Male , Massage/methods , Middle Aged , Neoplasms/physiopathology , Neoplasms/psychology , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pain/physiopathology , Pain/prevention & control , Qigong , Tai Ji
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