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1.
Article in English | MEDLINE | ID: mdl-38430165

ABSTRACT

Objective: To observe the clinical effect of mometasone furoate cream sodium Alginate Skin Repair Mask in the treatment of atopic dermatitis (AD). By assessing the combined use of these two treatments, the study aims to address a gap in knowledge regarding the effectiveness and safety of adjuvant therapies for AD, particularly in the context of Alginate Skin Repair Mask. Methods: Eighty patients were enrolled, including 42 males and 38 females aged 20-47 years, with an average age of (32.52±5.57) years, from July 2021 to July 2022, and the patients were divided into a single group (n=40) and a combined group (n=40) by random number table method. The patients in the single group were treated with mometasone furoate cream alone, and the patients in the combination group were treated with Alginate Skin Repair Mask on the basis of the treatment of the patients in the single group. The outcome measurements included clinical treatment effect, condition change (SCORAD score), quality of life (DLQI score), adverse reactions and disease recurrence were compared between the two groups. Both groups received treatment for 1 month. After the treatment of the patients, they were followed up for a period of 3 months. Results: The total effective rate of the single group was 80.0% (32/40), and that of the combined group was 97.5% (39/40) (P < .05). After treatment, the skin lesion area score, skin lesion degree score, pruritus insomnia score, and SCORAD total score in the combined group were significantly lower than those in the single group (35.03±9.41 vs 44.03±12.04) (all P < .05). The DLQI score of the combined group after treatment was significantly lower than that of the single group (3.72±1.53 vs 6.98±2.16) (P < .05). The incidence of adverse reactions in the single group was 22.5% (9/40), and the disease recurrence rate was 32.5% (13/40), while the incidence of adverse reactions in the combination group was 2.5% (1/40). The disease recurrence rate was 7.5% (3/40), and the incidence of adverse reactions and disease recurrence rate in the combination group were significantly lower than those in the single group (7.314, 7.812). Conclusion: Mometasone furoate cream sodium Alginate Skin Repair Mask has an ideal clinical effect in the treatment of atopic dermatitis. Compared with single mometasone furoate cream, the combination of sodium Alginate Skin Repair Mask can further improve the patient's condition, improve the quality of life of the patient, and reduce the risk of adverse reactions and disease recurrence. The higher total effective rate in the combined group indicates that the addition of Alginate Skin Repair Mask to the treatment regimen resulted in improved outcomes for patients with atopic dermatitis (AD). This translates to better control of the disease, reduction in symptoms, and overall improvement in the patient's condition.  However, it is important for clinicians to be aware that the use of topical glucocorticoids like mometasone furoate cream can potentially lead to adverse reactions. Some documented adverse reactions associated with long-term use of topical glucocorticoids include acne-like eruption, telangiectasia (dilation of small blood vessels), and local skin atrophy. By addressing multiple aspects of AD management, including skin barrier repair, moisturization, and inflammation control, the combination of mometasone furoate cream and Alginate Skin Repair Mask provides a more comprehensive treatment approach. This comprehensive approach may contribute to the observed reduction in recurrence rate in the combination group compared to the single group, where only mometasone furoate cream was used.

2.
Mol Cell ; 83(23): 4239-4254.e10, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38065062

ABSTRACT

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.


Subject(s)
Leukemia , Myelodysplastic Syndromes , Neoplasms , RNA Methylation , Serine-Arginine Splicing Factors , Humans , Leukemia/genetics , Myelodysplastic Syndromes/genetics , Neoplasms/genetics , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , Serine-Arginine Splicing Factors/genetics , RNA Methylation/genetics
3.
Proteins ; 91(8): 1065-1076, 2023 08.
Article in English | MEDLINE | ID: mdl-36964928

ABSTRACT

In recent years, the development of bispecific antibodies (bsAbs) has become a major trend in the biopharmaceutical industry. By simultaneously engaging two molecular targets, bsAbs have exhibited unique mechanisms of action that could lead to clinical benefits unattainable by conventional monoclonal antibodies. The type of structure used to construct a bsAb directly influences the distance, angle, degree of freedom, and affinity between the two antibody binding sites and the interaction between the two antigens or the cells where the antigens are located, which have been bound by the antibody. Consequently, the structure of the bsAb is one of the most vital factors affecting its function. Herein, we reported for the first time a novel basic module bsAb format, VFV (Variable domain-Fab-Variable domain). And then, the feasibility of the VFV format was demonstrated by constructing a series of engager-like basic module bsAbs. Next, a series of VFV bsAbs containing Fc (VFV-Ig), Fab (VFV-Fab), or Hinge (VFV-Hinge) were developed based on Hxb module, and all of them had adequate purity and activity. Finally, a T cell engager bsAb with the potential to overcome on-target off-tumor activity was constructed according to the structural characteristics of VFV, which validated that the VFV module can be used as a new brick for the construction of various bsAbs. In a word, the successful construction of this bsAb format for the first time not only enriches the arsenal of the bsAb format, but also provides inspiration for the construction of new bsAbs. Nevertheless, we are fully aware that as a proof-of-concept study, this paper has many shortcomings, and there is still a lot of work to be done to determine whether VFV can serve as a platform for drug development.


Subject(s)
Antibodies, Bispecific , Neoplasms , Humans , Antibodies, Monoclonal , Binding Sites, Antibody , T-Lymphocytes
4.
Front Vet Sci ; 9: 961354, 2022.
Article in English | MEDLINE | ID: mdl-36524231

ABSTRACT

Bacteriophages are viruses that infect bacteria. Bacteria and bacteriophages have been fighting for survival. Over time, the evolution of both populations has been affected. Pathogenic Flavobacteriaceae species including Riemerella anatipestifer mainly infects ducklings, geese, and turkeys. However, it does not infect humans, rats, or other mammals, and is a suitable and safe research object in the laboratory. Our previous study showed that there is a 10K genomic island in R. anatipestiferIn this study, we found another integrated 50K genomic islands and focused on the relationship between R. anatipestifer genomic islands and the RAP44 phage genome. The phage RAP44 genome was integrated into R. anatipestifer chromosome, and an evolutionary relationship was evident between them in our comparative analysis. Furthermore, the integrated defective RAP44 phage sequence had the function of integration, excision, and cyclization automatically. Integrases are important integration elements. The integrative function of integrase was verified in R. anatipestifer. The integrase with the attP site can be integrated stably at the attB locus of the R. anatipestifer genome. A recombinant strain can stably inherit and express the exogenous gene. By studying the integration between host bacterium and phage, we have provided evidence for the evolution of the genomes in R. anatipestifer.

5.
COPD ; 19(1): 353-364, 2022.
Article in English | MEDLINE | ID: mdl-36469629

ABSTRACT

We aimed to explore the role of antithrombin III (AT-III) activity in diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and chronic bronchitis, and its relationship with all-cause mortality of AECOPD patients. We performed univariate and multivariate Cox regression analyses of the factors determining all-cause mortality. We recruited 279 patients with AECOPD and 91 with chronic bronchitis. On admission, patients with AECOPD had lower AT-III activity (80.7 vs. 86.35%, p = 0.002) and higher neutrophil percentages (70.12 vs. 66.40%, p = 0.02) than those with chronic bronchitis. The patients who died were older (78 vs. 73 years, p < 0.001); had higher CRP (39.05 vs. 5.65 mg/L, p < 0.001), D-dimer (1.72 vs. 0.46 mg/L, p < 0.001), FIB (3.56 vs. 3.05 g/L, p = 0.01) levels; and exhibited lower AT-III activity (71.29 vs. 82.94%, p < 0.001) than the survivors. The AT-III area under the receiver operating characteristic curve for predicting COPD all-cause mortality was 0.75 (p < 0.001), optimal cutoff point 79.75%, sensitivity 86.8%, and specificity 57.1%. Multivariate Cox regression analyses showed that increased levels of CRP (HR = 1.005, p = 0.02), D-dimer (HR = 1.17, p = 0.01), WBC count (HR = 1.11, p = 0.002), and reduced AT-III activity (HR = 0.97, p = 0.02) were independent prognostic factors for all-cause mortality. Patients with AT-III ≤ 79.75% were 4.52 times (p = 0.001) more likely to die than those with AT-III > 79.75%. AT-III activity was lower in patients with AECOPD than in those with chronic bronchitis and is potentially useful as an independent predictor of all-cause mortality in patients with AECOPD: reduced AT-III activity and increased CRP and D-dimer levels indicate a higher risk of all-cause mortality.


Subject(s)
Antithrombin III , Bronchitis, Chronic , Pulmonary Disease, Chronic Obstructive , Humans , Biomarkers , Bronchitis, Chronic/mortality , Disease Progression , Hospital Mortality , Prognosis , Pulmonary Disease, Chronic Obstructive/mortality
6.
Front Vet Sci ; 9: 820914, 2022.
Article in English | MEDLINE | ID: mdl-35677933

ABSTRACT

Background: Porcine circovirus disease is currently the greatest threat to pig farming. Four main porcine circovirus genotypes are circulating worldwide. Objective: The study aimed to assess the prevalence of porcine circovirus genotypes in the central part of Shanxi province. Methods: We investigated the prevalence of porcine circovirus type 2 (PCV2), porcine circovirus type 3 (PCV3), and porcine circovirus type 4 (PCV4). Porcine circoviruses were analyzed by polymerase chain reaction (PCR) in the lung tissues of 180 pigs from 7 slaughterhouses in central Shanxi, China. Results: The prevalence of PCV2, PCV3, and PCV4 were 56.8, 80, and 9.4%, respectively, and the negative rate was 10% for all three pathogens. The co-infection with PCV2 + PCV3, PCV2 + PCV4, PCV3 + PCV4, and PCV2 + PCV3 + PCV4 were 47.2, 7.4, 7.4, and 5.6%, respectively. Among PCV4-positive samples, the positive rate of PCV4 + PCV2 was 52.9% (9/17), whereas that of PCV4 + PCV3 was 100% (17/17). On the other hand, PCV2 and PCV3 were detected in 57.1% (93/163) and in 78.5% (128/163) of PCV4-negative samples, respectively. Phylogenetic analysis demonstrated that PCV2, PCV3, and PCV4 were not in the same clade and were distant from each other. Conclusion: The high positive rates of PCV3, PCV2 + PCV3, and PCV3 + PCV4 suggest that PCV3 may play a decisive role in PCV2 and PCV4 infections. Therefore, further control of PCV3 is needed to reduce the spread of the virus.

7.
ACS Appl Mater Interfaces ; 14(3): 3685-3700, 2022 Jan 26.
Article in English | MEDLINE | ID: mdl-35023338

ABSTRACT

Depression is a mental health problem with typically high levels of distress and dysfunction, and 150 mg/L fluoride (F) can induce depression-like behavior. The development of depression is correlated with neuronal atrophy, insufficient secretion of monoamine neurotransmitters, extreme deviations from the normal microglial activation status, and immune-inflammatory response. Studies found that Se supplementation was related to the improvement of depression. In this study, we applied selenium nanoparticles (SeNPs) for F-induced depression disease mitigation by regulating the histopathology, metabolic index, genes, and protein expression related to the JAK2-STAT3 signaling pathway in vivo. Results showed that F and 2 mg Se/kg BW/day SeNPs lowered the dopamine (DA) content (P < 0.05), altered the microglial morphology, ramification index as well as solidity, and triggered the microglial neuroinflammatory response by increasing the p-STAT3 nuclear translocation (P < 0.01). Furthermore, F reduced the cortical Se content and the number of surviving neurons (P < 0.05), increasing the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 of the cortex (P < 0.01), accompanied by the depression-like behavior. Importantly, 1 mg Se/kg BW/day SeNPs alleviated the microglial ramification index as well as solidity changes and decreased the interleukin-1ß secretion induced by F by suppressing the p-STAT3 nuclear translocation (P < 0.01). Likewise, 1 mg Se/kg BW/day SeNPs restored the F-disturbed dopamine and noradrenaline secretion, increased the number of cortical surviving neurons, and reduced the vacuolation area, ultimately suppressing the occurrence of depression-like behavior through inhibiting the JAK2-STAT3 pathway activation. In conclusion, 1 mg Se/kg BW/day SeNPs have mitigation effects on the F-induced depression-like behavior. The mechanism of how SeNPs repair neural functions will benefit depression mitigation. This study also indicates that inhibiting the JAK/STAT pathway can be a promising novel treatment for depressive disorders.


Subject(s)
Biocompatible Materials/pharmacology , Depression/drug therapy , Microglia/drug effects , Nanoparticles/chemistry , Selenium/pharmacology , Animals , Behavior, Animal/drug effects , Biocompatible Materials/chemistry , Depression/chemically induced , Fluorides , Male , Materials Testing , Mice , Mice, Inbred Strains , Selenium/chemistry
8.
Vet Med Sci ; 7(4): 1339-1346, 2021 07.
Article in English | MEDLINE | ID: mdl-34021725

ABSTRACT

BACKGROUND: Porcine respiratory diseases remain the biggest challenge in pig-based food production and are a public health concern. Despite control measures, persistent outbreaks have been reported worldwide. OBJECTIVE: To establish an early detection mechanism for pig farm disease outbreaks based on slaughterhouse risk and environmental assessment. METHODS: We investigated the prevalence and risk factors of porcine respiratory disease-causing pathogens including Mycoplasma hyopneumoniae (MHP), porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS). Polymerase chain reaction (PCR) was used to analyse the lungs of 491 pigs from 19 slaughterhouses across 11 cities in Shanxi Province, China. RESULTS: PCR detected MHP, PCV2, PPRSV and HPS in 76.99%, 67.00%, 11.82% and 19.55% of the samples, respectively; 10.12% were negative for all four pathogens. Co-positivity rates for two and three pathogens were identified. The results confirmed significant correlations between PCV2 and MHP (p = .001, p < .05), HPS and PCV2 (p = .01, p < .05) and MHP and PRRSV (p = .01, p < .05). No significant correlation was observed between HPS and MHP (p = .067, p > .05). Positive MHP and PCV2 rates were low in areas with high vegetation coverage. The overall pathogen positivity rate was higher in both lower and higher temperature environments. CONCLUSIONS: Interactions among pathogens may increase disease severity. Furthermore, environmental assessment and pathogen surveillance within pig slaughterhouses can be an effective approach for early detection and mitigation of new disease threats before broad dissemination occurs among a herd.


Subject(s)
Circoviridae Infections/veterinary , Haemophilus Infections/veterinary , Pneumonia of Swine, Mycoplasmal/epidemiology , Porcine Reproductive and Respiratory Syndrome/epidemiology , Abattoirs , Animals , China/epidemiology , Circoviridae Infections/epidemiology , Circoviridae Infections/virology , Circovirus/isolation & purification , Haemophilus Infections/epidemiology , Haemophilus Infections/microbiology , Haemophilus parasuis/isolation & purification , Mycoplasma hyopneumoniae/isolation & purification , Pneumonia of Swine, Mycoplasmal/microbiology , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/isolation & purification , Prevalence , Risk Factors , Sus scrofa , Swine
9.
Trop Anim Health Prod ; 53(2): 299, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33939008

ABSTRACT

Bovine viral diarrhea virus (BVDV) and peste des petits ruminants virus (PPRV) are two important pathogens associated with a variety of disease syndromes that result in substantial financial losses in animal husbandry. This study was performed to assess the seroprevalence of antibodies to BVDV and PPRV among alpacas raised in Shanxi Province of northern China. Serum samples were obtained from 246 alpacas in Taiyuan (n=182), Xinzhou (n=31), and Jinzhong cities (n=33) of Shanxi Province, and serological testing was carried out using the competitive enzyme-linked immunosorbent assay. Overall seroprevalence to BVDV was 3.25% (95% CI 1.03-5.47), and seropositive alpacas were found only in Taiyuan City. The overall PPRV seroprevalence in alpacas was 28.86% (95% CI 23.20-34.52). While no PPRV-seropositive alpacas were found in Xinzhou City, the seroprevalence of PPRV was 90.91% (95% CI 81.10-100.72) in Jinzhong City and 22.53% (95% CI 16.46-28.60) in Taiyuan City, respectively, which showed a statistically significant difference. To our knowledge, the present work is the first report on seroprevalence of BVDV and PPRV in alpacas in China, which provides baseline information for the control of infection.


Subject(s)
Camelids, New World , Goat Diseases , Peste-des-Petits-Ruminants , Peste-des-petits-ruminants virus , Animals , Antibodies, Viral , China/epidemiology , Diarrhea/veterinary , Goats , Peste-des-Petits-Ruminants/epidemiology , Seroepidemiologic Studies
10.
Nat Commun ; 11(1): 1391, 2020 Mar 13.
Article in English | MEDLINE | ID: mdl-32170177

ABSTRACT

Memory devices with high speed and high density are highly desired to address the 'memory wall' issue. Here we demonstrated a highly scalable, three-dimensional stackable ferroelectric diode, with its rectifying polarity modulated by the polarization reversal of Hf0.5Zr0.5O2 films. By visualizing the hafnium/zirconium lattice order and oxygen lattice order with atomic-resolution spherical aberration-corrected STEM, we revealed the correlation between the spontaneous polarization of Hf0.5Zr0.5O2 film and the displacement of oxygen atom, thus unambiguously identified the non-centrosymmetric Pca21 orthorhombic phase in Hf0.5Zr0.5O2 film. We further implemented this ferroelectric diode in an 8 layers 3D array. Operation speed as high as 20 ns and robust endurance of more than 109 were demonstrated. The built-in nonlinearity of more than 100 guarantees its self-selective property that eliminates the need for external selectors to suppress the leakage current in large array. This work opens up new opportunities for future memory hierarchy evolution.

11.
3 Biotech ; 10(3): 86, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32089981

ABSTRACT

The development of rapid, simple, and sensitive diagnostic methods for identification of avian infectious bronchitis virus (IBV) is crucial for the effective control of avian infectious bronchitis. In the present study, a tandemly arranged multiepitope peptide (named SEMN) was designed with four antigenic regions derived from four major structural proteins of IBV. Then, we performed codon optimization of SEMN gene by changing the codon-adaptation index from 0.45 to 0.94 and expressed the optimized gene in codon bias-adjusted Escherichia coli Rosetta (DE3), followed by determination of the immunoreactivity of the purified protein. Bioinformatics analysis of SEMN showed a high antigenicity, surface probability and hydrophilicity. The recombinant protein rSEMN was expressed both in soluble forms and as inclusion bodies, and the molecular weight of rSEMN was about 39 kDa. The preliminary diagnostic performance of rSEMN was confirmed by Western blotting analysis using chicken anti-IBV polyclonal antibodies. Further studies are needed to evaluate the immunogenicity in animal models and to give a final assessment of the diagnostic utility of this recombinant multi-epitope antigen.

12.
Food Funct ; 11(1): 1155-1164, 2020 Jan 29.
Article in English | MEDLINE | ID: mdl-31872845

ABSTRACT

Bone is the main target of fluorosis, and it has been perfectly elaborated that a moderate dosage of calcium (Ca) can alleviate bone fluorosis. However, whether Ca can alleviate fluorosis through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway has not yet been reported. Hence, we evaluated the histopathological structure, the imbalance of the biochemical index of bone metabolism, and the expression levels of PI3K/AKT apoptosis signaling pathway-related genes in rats treated with sodium fluoride (NaF, F) and/or calcium carbonate (CaCO3) for 120 days. Our results suggest that 100 mg L-1 NaF induced histopathological injury as alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (StrACP) activity increased, with a decrease in the serum Ca levels (p < 0.05). Moreover, the results of qRT-PCR and western blotting showed that F increased the expression levels of transglutaminase 2 (TGM2), focal adhesion kinase (FAK), PI3K, AKT, forkhead box O1 (Foxo1), Bcl-2 interacting mediator of cell death (BIM), Bcl2-associated x protein (Bax) and Caspase 3 (p < 0.05, p < 0.01). It also decreased the expression of AnnexinA5 (Anxa5), 3'-phosphoinositide-dependent kinase 1 (PDK1) and B-cell lymphoma-2 (Bcl-2) (p < 0.05, p < 0.01), which finally activated the PI3K/AKT pathway. On the other hand, CaCO3 supplementation reversed the histopathological injury along with the levels of ALP, StrACP and serum Ca, alleviating the gene expression levels of PI3K/AKT pathway-related markers. Altogether, we can conclude that CaCO3 supplementation mitigated F-induced bone damage via the PI3K/AKT signaling pathway.


Subject(s)
Bone and Bones/drug effects , Calcium/metabolism , Fluorides/adverse effects , Signal Transduction , Animals , Apoptosis , Bone and Bones/pathology , Fluoride Poisoning/therapy , Male , Phosphatidylinositol 3-Kinases/metabolism , Protein Glutamine gamma Glutamyltransferase 2 , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley
13.
Mol Cell ; 75(6): 1188-1202.e11, 2019 09 19.
Article in English | MEDLINE | ID: mdl-31399345

ABSTRACT

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.


Subject(s)
5-Methylcytosine/metabolism , Embryo, Nonmammalian/embryology , Embryonic Development/physiology , RNA Stability/physiology , RNA, Messenger, Stored/metabolism , Zebrafish/embryology , Animals , HeLa Cells , Humans , Mice , RNA, Messenger, Stored/genetics , Zebrafish/genetics
14.
HLA ; 94(2): 181-182, 2019 08.
Article in English | MEDLINE | ID: mdl-31041847

ABSTRACT

The novel KIR2DL4*00603 allele differs from the closest allele KIR2DL4*00602 by a silent mutation.


Subject(s)
Alleles , Asian People/genetics , Ethnicity/genetics , Receptors, KIR2DL4/genetics , Base Sequence , Exons/genetics , Genetic Variation , Humans
15.
HLA ; 94(2): 184-185, 2019 08.
Article in English | MEDLINE | ID: mdl-31044496

ABSTRACT

The novel KIR2DL4*037 allele differs from the closest allele KIR2DL4*00501 by a single missense mutation.


Subject(s)
Alleles , Asian People/genetics , Ethnicity/genetics , Receptors, KIR2DL4/genetics , Base Sequence , Exons/genetics , Humans , Mutation, Missense/genetics
16.
J Agric Food Chem ; 67(16): 4611-4622, 2019 Apr 24.
Article in English | MEDLINE | ID: mdl-30942077

ABSTRACT

Cadmium (Cd) is a toxic metal leading to multiple forms of organ damage. Zinc (Zn) was reported as a potential antagonist against Cd toxicity. The present study investigates the antagonistic effect of Zn (20 µM) on Cd (20 or 50 µM) cytotoxicity in macrophages in vitro. The results shows that Cd exposure caused dose-dependent morphologic and ultrastructural alterations in RAW 264.7 macrophages. Zn supplement significantly inhibited Cd cytotoxicity in RAW 264.7 or HD-11 macrophages by mitigating cell apoptosis, excessive ROS output, and mitochondrial membrane depolarization. Notably, Zn supplement for 12 h remarkably prevented intracellular Cd2+ accumulation in 20 µM (95.99 ± 9.93 vs 29.64 ± 5.08 ng/106 cells; P = 0.0008) or 50 µM Cd (179.78 ± 28.66 vs 141.62 ± 22.15 ng/106 cells; P = 0.003) exposed RAW 264.7 cells. Further investigation found that Cd promoted metallothioneins (MTs) and metal regulatory transcription factor 1 (MTF-1) expression in RAW 264.7 macrophages. Twenty µM Zn supplement dramatically enhanced MTs and MTF-1 levels in Cd-exposed RAW 264.7 macrophages. Intracellular Zn2+ chelation or MTF-1 gene silencing inhibited MTs synthesis in Cd-exposed RAW 264.7 macrophages, which was accompanied by the declined expression of MTF-1, indicating that regulation of Zn on MTs was partially achieved by MTF-1 mobilization. In conclusion, this study demonstrates the antagonism of Zn against Cd cytotoxicity in macrophages and reveals its antagonistic mechanism by preventing Cd2+ bioaccumulation and promoting MTs expression.


Subject(s)
Cadmium Poisoning/metabolism , Cadmium/metabolism , Metallothionein/metabolism , Zinc/pharmacology , Animals , Apoptosis/drug effects , Cadmium/toxicity , Cadmium Poisoning/drug therapy , Cadmium Poisoning/etiology , Cadmium Poisoning/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Dietary Supplements/analysis , Humans , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Metallothionein/genetics , Mice , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription Factor MTF-1
17.
Methods Mol Biol ; 1870: 237-248, 2019.
Article in English | MEDLINE | ID: mdl-30539560

ABSTRACT

5-Methylcytosine (m5C) is a posttranscriptional RNA modification identified in both stable and highly abundant tRNAs and rRNAs, and in mRNAs. Many known or novel m5C sites have been validated by using advanced high-throughput techniques combined with next-generation sequencing (NGS), especially RNA bisulfite sequencing (RNA-BisSeq). Here we introduce an optimized RNA-BisSeq method by using ACT random hexamers to prime the reverse transcription of bisulfite-treated RNA samples to detect the m5C sites.


Subject(s)
5-Methylcytosine , Computational Biology/methods , High-Throughput Nucleotide Sequencing , RNA Processing, Post-Transcriptional , RNA/genetics , 5-Methylcytosine/metabolism , Chromatography, High Pressure Liquid , Databases, Nucleic Acid , High-Throughput Nucleotide Sequencing/methods , Mass Spectrometry , Methylation , RNA/chemistry , RNA/metabolism , RNA, Messenger/genetics , Software
18.
BMC Vet Res ; 14(1): 363, 2018 Nov 21.
Article in English | MEDLINE | ID: mdl-30463541

ABSTRACT

BACKGROUND: Chicken erythrocytes are involved in immunity through binding of toll-like receptors (TLRs) with their ligands to activate downstream signaling and lead to cytokine production in erythrocytes. Some avian ß-defensins (AvBDs) are constitutively expressed in tissues and some others can be induced by various bacteria and viruses. However, the expression of AvBDs in erythrocytes has not yet been studied extensively. RESULTS: The transcripts of eight AvBDs (AvBD1 to AvBD7, and AvBD9) and liver-expressed antimicrobial peptide-2 (LEAP-2) were found in normal chicken erythrocytes. The expression levels of AvBD2, 4 and 7 were significantly increased (P < 0.01), whereas the levels of AvBD1, 6 and 9 were significantly decreased (P < 0.01) after Marek's disease virus (MDV) infection. The mRNA expression level of LEAP-2 was not significantly changed after MDV infection. Highest viral nucleic acid (VNA) of MDV in the feather tips among the tested time points was found at 14 days post-infection (d.p.i.). In addition, 35 MD5-related gene segments were detected in the erythrocytes at 14 d.p.i. by transcriptome sequencing. CONCLUSIONS: These results suggest that the AvBDs in chicken erythrocytes may participate in MDV-induced host immune responses.


Subject(s)
Chickens/blood , Erythrocytes/metabolism , Marek Disease/blood , Poultry Diseases/blood , beta-Defensins/blood , Animals , Antimicrobial Cationic Peptides/blood , Antimicrobial Cationic Peptides/genetics , Chickens/genetics , Feathers/virology , Male , Marek Disease/genetics , Poultry Diseases/genetics , Poultry Diseases/virology , RNA, Messenger/blood , Viral Load/veterinary , beta-Defensins/genetics
19.
Ecotoxicol Environ Saf ; 163: 331-339, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30059877

ABSTRACT

Cadmium (Cd) is one of the most toxic metals released into the environment. Here, we investigated the protective role of Zn2+ and/or N-acetyl-L-cysteine (NAC) against Cd cytotoxicity in the erythrocytes of Arbor Acres (AA) broiler chickens. Four hundred one-day-old AA chickens were divided into 12 groups for in vitro and in vivo studies. Zn2+ and/or NAC was given to the Cd exposed AA chickens to assess their protective roles. This was accomplished by investigating nuclear morphological abnormalities, oxidative stress (SOD, CAT, GPx, GSH and T-AOC), cell apoptosis, ROS accumulation and mitochondrial membrane potential (MMP). Results showed that Cd led to dose- and time-dependent cytotoxicity in the erythrocytes of AA chickens characterized by morphological abnormalities, nucleus damage, increased apoptosis rate and antioxidants depletion. Zn2+ or NAC significantly decreased the erythrocyte apoptosis, ROS production and mitochondrial membrane depolarization caused by Cd. SOD, CAT, GPx, GSH and T-AOC activities significantly decreased both in serum and erythrocytes of Cd exposed AA chickens. The supplementation with Zn2+ or NAC alleviated Cd induced oxidative stress through promoting SOD or GPx/GSH activities respectively. NAC presented a better role in reducing apoptosis, improving antioxidant activities more than Zn2+ in vitro. The combined use of Zn2+ and NAC enhanced cytoprotection in Cd exposed erythrocytes of AA chickens compared to Zn2+ or NAC alone. In conclusion, Zn2+ and NAC exerted remarkable protective roles in Cd exposed erythrocytes of AA chickens by inhibiting cell apoptosis and oxidative stress, and this provides a promising approach to antagonize Cd poisoning in poultry.


Subject(s)
Acetylcysteine/pharmacology , Antioxidants/pharmacology , Cadmium/toxicity , Erythrocytes/drug effects , Zinc/pharmacology , Animals , Apoptosis/drug effects , Chickens , Oxidative Stress/drug effects
20.
Int J Nurs Stud ; 82: 129-138, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29631145

ABSTRACT

BACKGROUND: Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. OBJECTIVES: This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. DESIGN: Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. METHODS: Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals (The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. RESULTS: Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. CONCLUSIONS: Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification.


Subject(s)
Moxibustion/methods , Muscle Spasticity/therapy , Stroke/complications , Activities of Daily Living , Humans , Muscle Spasticity/etiology , Muscle Spasticity/physiopathology , Randomized Controlled Trials as Topic , Stroke/physiopathology
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