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PURPOSE: To investigate whether Dicliptera chinensis polysaccharide (DCP) can alleviate radiation-induced fibrosis of masseter and head and neck skin. METHODS: SD rats were divided into the control, the irradiation (IR), the IR + low dose DCP (200 mg/kg), and the IR + high dose DCP (400 mg/kg) groups. The head and neck of rats in the last 3 groups received a single dose of 18 Gy X-ray. At 1st, 2nd, 4th week (w) after radiation, haematoxylin and eosin staining were performed on masseter and skin to observe the histopathological changes; immunohistochemistry staining was performed to observe the pathological changes of the skin; Masson staining was performed on masseter and skin to observe the collagen deposition; western blot analysis was used on masseter to calculate the relative transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF) expressions; ELISA was used to detect the contents of TGF-ß1 and CTGF in skin and the contents of type I and type III collagens in masseter and skin. RESULTS: In terms of skin, compared to the IR group, the IR + high-dose DCP group exhibited relatively smaller changes in skin structure, lower levels of TGF-ß1 and CTGF; thinner skin thickness was observed at the 4th w after radiation; and the positive rates of collagen fibre and the optical densities of type I and type III collagens were lower at the 2nd and 4th w. For the masseter, compared to the IR group, the morphological changes were improved and the expression levels of TGF-ß1 and CTGF proteins decreased in the 2 DCP dose groups at 2nd and 4th w. CONCLUSION: DCP can reduce the formation and accumulation of type I and type III collagens after IR and ameliorate radiation-induced fibrosis of masseter and skin by down-regulating the expressions of TGF-ß1 and CTGF.
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Carbon and nitrogen play a fundamental role in the architecture of fungal biofilm morphology and metabolite production. However, the regulatory mechanism of nutrients remains to be fully understood. In this study, the formation of Beauveria bassiana biofilm and the production of (R)-2-(4-Hydroxyphenoxy)propanoic acid in two media with different carbon and nitrogen sources (GY: Glucose as a carbon source and yeast extract as a nitrogen source, MT: Mannitol as a carbon source and tryptone as a nitrogen source) were compared. R-HPPA production increased 2.85-fold in media MT than in media GY. Different fungal biofilm morphology and architecture were discovered in media GY and MT. Comparative transcriptomics revealed up-regulation of mitogen-activated protein kinase (MAPK) pathway and polysaccharides degradation genes affecting mycelial morphology and polysaccharides yield of the extracellular polymeric substances (EPS) in MT medium biofilms. Upregulation of genes related to NADH synthesis (carbon metabolism, amino acid metabolism, glutamate cycle) causes NADH accumulation and triggers an increase in R-HPPA production. These data provide a valuable basis for future studies on regulating fungal biofilm morphology and improving the production of high-value compounds.
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The unspecific peroxygenase (UPO) from Cyclocybe aegerita (AaeUPO) can selectively oxidize C-H bonds using hydrogen peroxide as an oxygen donor without cofactors, which has drawn significant industrial attention. Many studies have made efforts to enhance the overall activity of AaeUPO expressed in Komagataella phaffii by employing strategies such as enzyme-directed evolution, utilizing appropriate promoters, and screening secretion peptides. Building upon these previous studies, the objective of this study was to further enhance the expression of a mutant of AaeUPO with improved activity (PaDa-I) by increasing the gene copy number, co-expressing chaperones, and optimizing culture conditions. Our results demonstrated that a strain carrying approximately three copies of expression cassettes and co-expressing the protein disulfide isomerase showed an approximately 10.7-fold increase in volumetric enzyme activity, using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) as the substrate. After optimizing the culture conditions, the volumetric enzyme activity of this strain further increased by approximately 48.7%, reaching 117.3 U/mL. Additionally, the purified catalytic domain of PaDa-I displayed regioselective hydroxylation of R-2-phenoxypropionic acid. The results of this study may facilitate the industrial application of UPOs. KEY POINTS: ⢠The secretion of the catalytic domain of PaDa-I can be significantly enhanced through increasing gene copy numbers and co-expressing of protein disulfide isomerase. ⢠After optimizing the culture conditions, the volumetric enzyme activity can reach 117.3 U/mL, using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) as the substrate. ⢠The R-2-phenoxypropionic acid can undergo the specific hydroxylation reaction catalyzed by catalytic domain of PaDa-I, resulting in the formation of R-2-(4-hydroxyphenoxy)propionic acid.
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Oxigenases de Função Mista , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/química , Saccharomycetales/genética , Saccharomycetales/enzimologia , Saccharomycetales/metabolismo , Dosagem de Genes , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Expressão Gênica , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/químicaRESUMO
Objective: Radiotherapy for head and neck can damage the salivary gland cells, which can easily result in xerostomia. No effective treatment for radiation-induced salivary gland dysfunction currently exists. Thus, we aimed to study the protective effect of Dicliptera chinensis polysaccharides (DCP) on the prevention of submandibular gland (SMG) cell damage caused by radiotherapy in Sprague-Dawley rats. Design: Mechanical enzyme digestion was used to extract primary rat SMG cells. A radiation injury model was established by treating these cells with a dose of 8 Gy, followed by intervention using different DCP concentrations. The cell counting kit 8 assay was used to determine the inhibition rate of SMG cells in each group. The rates of apoptosis and cell cycle progression were detected using flow cytometry. Expression of the Mre11/Rad50/Nbs1 complex (MRN) was detected using western blotting. Results: DCP increased the proliferation of SMG cells after irradiation, and cell growth activity positively correlated with polysaccharide concentration. Flow cytometry analysis of SMG cell apoptosis revealed that DCP markedly reduced the total apoptosis rate after irradiation, especially the early apoptosis rate. Cell cycle results suggested that DCP reduced the number of cells in the S and G2 phases after irradiation and alleviated the S and G2 blocks. Western blot results indicated that the expression of Mre11, Rad50, and Nbs1 decreased in the radiation-injured group, whereas their expression increased after DCP treatment. Conclusions: DCP can protect the rat SMG cells after radiation and be used as a protective agent against salivary gland cell damage caused by radiotherapy.
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RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants' spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid-liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.
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The salivary gland (SGS) is a kind of organ vulnerable to ionizing radiation. Radiotherapy is an important treatment for head and neck tumors, but in the process of radiotherapy, tumor cells will be injured by radiation to a certain extent. Infrared-induced DNA double-strand break (IR-DSBs) is one of the most serious DNA damage. DNA repair proteins such as Nymegan rupture syndrome protein 1 (NBS1) play a key role in the identification and repair of DNA damage. but the interaction between SSB1 and NBS1 has not been elucidated. In this study, we irradiated rat submandibular gland (SMG) cells, which were either infected with a rAdE5-SSB1-1p2-shRNA recombinant adenovirus to silence SSB or a control virus, to explore the effect of IR on the expression NBS1 in the absence of SSB. Our results showed that the SSB1 mRNA transcripts and protein expression of SSB1 and NBS1 initially increased and decreased later with increased doses. The relative expression reached the highest levels when the SMG cells were irradiated with 2Gy of IR. Silencing the SSB1 gene suppressed the expression of both SSB1 and NBS1 regardless of irradiation. The expression of NBS1 decreased when the SSB1 gene was silenced. We concluded that IR affected the expression of both SSB1 and NBS1 and there is a synergistic effect on IR-induced NBS1 suppression and DSBs repair in SMG cells. These observations shed light on further investigation and elucidation of IR-caused DNA repair mechanisms.
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Proteínas de Ciclo Celular , Proteínas Nucleares , Glândula Submandibular , Animais , Ratos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA , Reparo do DNA/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Glândula Submandibular/metabolismoRESUMO
Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was superior to the Sm mRNA-LNP vaccine at inducing antibody and cellular immune responses in mice. Evaluation of the immunogenicity and efficacy of the S mRNA vaccine in piglets confirmed that it induced robust PEDV-specific humoral and cellular immune responses in vivo. Importantly, the S mRNA-LNP vaccine not only protected actively immunized piglets against PEDV but also equipped neonatal piglets with effective passive anti-PEDV immunity in the form of colostrum-derived antibodies after the immunization of sows. Our findings suggest that the PEDV-S mRNA-LNP vaccine is a promising candidate for combating PEDV infection.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Vacinas Virais , Animais , Suínos , Feminino , Camundongos , Anticorpos Antivirais , Vacinas de mRNA , Vírus da Diarreia Epidêmica Suína/genética , Vacinas Virais/genética , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Glicoproteína da Espícula de Coronavírus/genética , Diarreia , RNA Mensageiro/genética , Doenças dos Suínos/prevenção & controleRESUMO
We propose three novel spatial data selection techniques for particle data in VR visualization environments. They are designed to be target- and context-aware and be suitable for a wide range of data features and complex scenarios. Each technique is designed to be adjusted to particular selection intents: the selection of consecutive dense regions, the selection of filament-like structures, and the selection of clusters-with all of them facilitating post-selection threshold adjustment. These techniques allow users to precisely select those regions of space for further exploration-with simple and approximate 3D pointing, brushing, or drawing input-using flexible point- or path-based input and without being limited by 3D occlusions, non-homogeneous feature density, or complex data shapes. These new techniques are evaluated in a controlled experiment and compared with the Baseline method, a region-based 3D painting selection. Our results indicate that our techniques are effective in handling a wide range of scenarios and allow users to select data based on their comprehension of crucial features. Furthermore, we analyze the attributes, requirements, and strategies of our spatial selection methods and compare them with existing state-of-the-art selection methods to handle diverse data features and situations. Based on this analysis we provide guidelines for choosing the most suitable 3D spatial selection techniques based on the interaction environment, the given data characteristics, or the need for interactive post-selection threshold adjustment.
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Luban locks with mortise and tenon structure have structural diversity and architectural stability, and it is extremely challenging to synthesize Luban lock-like structures at the molecular level. In this work, we report the cocrystallization of two structurally related atom-precise fcc silver nanoclusters Ag110 (SPhF)48 (PPh3 )12 (Ag110 ) and Ag14 (µ6 -S)(SPhF)12 (PPh3 )8 (Ag14 ). It is worth noting that the Ag110 cluster is the first compound to simulate the complex Luban lock structure at the molecular level. Meanwhile, Ag110 is the largest known fcc-based silver nanocluster, so far, there is no precedent for fcc silver nanocluster with more than 100 silver atoms. DFT calculations show that Ag110 is a 58-electron superatom with an electronically closed shell1S2 1P6 1D10 2S2 1F14 2P6 1G18 . Ag110 â Ag14 can rapidly catalyze the reduction of 4-nitrophenol within 4â minutes. In addition, Ag110 presents clear structural evidence to reveal the critical size and mechanism of the transformation of metal core from fcc stacking to quasi-spherical superatom. This research work provides an important structural model for studying the nucleation mechanism and structural assembly of silver nanoclusters.
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Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. We developed a novel adjuvant to improve the targeting of lymph nodes. CpG were modified with lipid and glycopolymers by the combination of photo-induced RAFT polymerization and click chemistry, and the novel adjuvant was termed as lipid-glycoadjuvant@AuNPs (LCpG). OVA protein was used as model antigen and melanoma model was established to test the immunotherapy effect of the adjuvant. In tumor model, the antitumor effect and mechanism of LCpG on the response of CTLs were examined by flow cytometry and cell cytotoxicity assay. The effects of LCpG on macrophage polarization and Tregs differentiation in tumor microenvironment were also studied by cell depletion assay and cytokine neutralization assay. We also tested the therapeutic effect of the combination of the adjuvant and anti-PD-1 treatment. LCpG could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen-specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, regulated Treg and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.
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Vacinas Anticâncer , Melanoma , Nanopartículas Metálicas , Animais , Camundongos , Microambiente Tumoral , Interferon gama/metabolismo , Ouro/metabolismo , Ouro/farmacologia , Linfócitos T CD8-Positivos , Adjuvantes Imunológicos , Melanoma/metabolismo , Lipídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Bacillus subtilis was applied in peat-based soilless cultivation systems containing a mixed substrate (peat:vermiculite:perlite = 2:1:1, v/v/v) and irrigated by one-strength or four-strength Hoagland's nutrient solution to explore whether it can alleviate inhibition by higher-nutrient solutions (four-strength) and bring benefits to improvements of quality. The results showed that higher-nutrient solutions improved the flavor quality of cucumber fruit; especially, the contents of (E,Z)-2,6-nonadienal and (E)-2-Nonenal were effectively increased, which are the special flavor substances of cucumber. B. subtilis K424 effectively improved growth performance, photosynthetic capacity, vitamin C content, soluble sugars, soluble protein, and total pectin in cucumber under higher nutrition solution conditions. Compared with the higher solution treatment, the bacterial diversity significantly increased, whereas the presence of fungi had no significant difference following the B. subtilis K424 application. Moreover, B. subtilis K424 reduced the relative abundance of Actinomadura and promoted that of the Rhodanobacter, Bacillus, Pseudomonas, Devosiaceae, and Blastobotrys genera. Redundancy analysis showed that Bacillus, Rhodanobacter, and Blastobotrys were positively correlated with the substrate enzyme of sucrase, catalase, and urease. This study provides insight that B. subtilis K424 mitigated the deleterious effects of high levels of nutrition solution on cucumber growth and quality by improving the substrate enzyme, regulating the microbial community structure, and enhancing the photosynthetic capacity.
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Background: Recently, the demand for minimally invasive techniques in kidney transplantation (MIKT) has increased. However, there is only a limited number of studies on MIKT, especially in pediatric kidney transplants. Hence, we evaluated whether there is a difference between the super-minimal incision technique in pediatric kidney transplantation (SMIPKT) and conventional kidney transplantation (CKT). Methods: Between December 2018 and November 2021, 34 patients who underwent pediatric kidney transplantation with a follow-up of 1 month were enrolled. A paired kidney analysis was performed to minimize donor variability and bias. The SMIPKT and CKT groups included 17 patients. Results: There was no difference in baseline clinical characteristics, including age, sex, the donor/ recipient weight ratio (DRWR), choice of dialysis modality, pretransplant dialysis time, BMI, renal artery number, cause of ESRD, DGF, length of the kidney and cold ischemic time, tacrolimus concentration at 3 and 7 days, serum creatinine at 1 month and postoperative complication rate between the SMIPKT and CKT groups (all P > 0.05). However, the length of the incision, operation time, intraoperative bleeding, postoperative drainage volume within 24 h and Vancouver scar scale at 1 month were statistically significant (all P < 0.05). Conclusion: Compared with CKT, our results indicated that SMIPKT showed more satisfactory cosmetic results, shorter SMIPKT operating time, and reduced intraoperative bleeding and postoperative drainage volume within 24 h. There were also no statistical differences in postoperative complications. Hence, we suggest that SMIPKT is an appropriate method for pediatric kidney transplantation.
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ABSTARCT: BACKGROUND: Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. METHODS: gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. RESULTS: gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. CONCLUSIONS: We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments.
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Antineoplásicos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Ouro/química , Nanopartículas Metálicas/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
To evaluate the diagnostic significance of serum miR-192-5p for atherosclerosis (AS) and explore the effect of miR-192-5p on cell proliferation and migration of vascular smooth muscle cells (VSMCs). The expression level of serum miR-192-5p was measured by qRT-PCR. Correlations of miR-192-5p with CRP and CIMT were evaluated by Pearson correlation coefficient. The diagnostic significance of miR-192-5p was assessed using an ROC curve. CCK-8 assay and Transwell assay were used to analyze the effect of miR-192-5p on cell proliferation and migration. Luciferase reporter gene assay was used to evaluate the effect of miR-192-5p with ATG7. The expression level of serum miR-192-5p in AS patients was significantly high compared with healthy controls. miR-192-5p was positively correlated with CRP and CIMT, and it has diagnostic value for AS. In vitro cell experiments confirmed that overexpression of miR-192-5p could promote cell proliferation and migration of VSMCs. miR-192-5p directly targets ATG7 in VSMCs. Down-regulation of miR-192-5p level increased ATG7 expression and inhibited cell proliferation and migration. miR-192-5p may be a new biomarker for the diagnosis of AS and may provide new idea for the treatment of AS.
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Aterosclerose/diagnóstico , Proteína 7 Relacionada à Autofagia/genética , Biomarcadores/química , MicroRNAs/genética , Músculo Liso Vascular/citologia , Idoso , Aterosclerose/genética , Aterosclerose/imunologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Células Cultivadas , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Receptores Imunológicos/sangue , Regulação para CimaRESUMO
Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.
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Fixed dose combinations (FDCs) offer an accessible way to simplify complex therapeutic regimens by the simultaneous presentation of multiple drugs in a single entity to the patient. However, encapsulation of hydrophobic drugs into FDCs possess a number of technical challenges. Electrospinning comprises a convenient way to incorporate multiple hydrophobic drugs into a single formulation in a single step, via the use of an appropriate organic solvent system during fabrication. In this study, we report a series of novel fiber formulations comprising ethyl cellulose loaded with two hydrophobic drugs, spironolactone and nifedipine, either individually or in combination. The drugs are found to be present in the fibers in the form of amorphous solid dispersions, and these are stable at room temperature for 4 months. The products showed extended release profiles over more than 30 h. This formulation strategy offers potential to manage chronic cardiovascular conditions and overcome patient related non-adherence by providing a simplified treatment model.
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Doenças Cardiovasculares , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Interações Hidrofóbicas e Hidrofílicas , SolventesRESUMO
OBJECTIVES: Atherosclerosis is a common vascular disease. MiR-637 has been demonstrated to be low-expressed in hypertensive patients, and atherosclerosis is closely related to hypertension. Therefore, this study speculated that miR-637 may play an important role in the development of atherosclerosis. In brief, this study examined the expression level of miR-637 in patients with atherosclerosis and further analyzed its clinical value in patients with atherosclerosis. METHODS: The expression level of miR-637 was detected in serum from 86 patients with atherosclerosis and 75 healthy controls by using quantitative reverse transcription-polymerase chain reaction. The receiver operating characteristic curve was used to assess the diagnostic value of miR-637 in atherosclerosis. Pearson's correlation analysis was performed to evaluate the relationship between serum miR-637 and different clinical parameters. The prognostic value of miR-637 in atherosclerosis was analyzed by the Kaplan-Meier survival curve and multivariate cox regression analysis. RESULTS: Compared with healthy individuals, miR-637 was downregulated in the serum of atherosclerosis patients. The receiver operating characteristic curve suggested the high diagnostic value of miR-637 for atherosclerosis, with the AUC of 0.853, specificity of 77.9%, and sensitivity of 80.0%. The expression level of miR-637 was negatively correlated with CIMT (r = -0.8101, P < 0.0001) and CRP (r = -0.6154, P < 0.0001), respectively. Survival analysis indicated that miR-637 was also found to be an independent prognostic factor for atherosclerosis. CONCLUSIONS: MiR-637 is a potential noninvasive diagnostic marker of atherosclerosis and has important predictive value for the occurrence of future cardiovascular events.
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Aterosclerose/genética , Doenças das Artérias Carótidas/genética , MicroRNA Circulante/genética , MicroRNAs/genética , Idoso , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Fatores de RiscoRESUMO
This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04-1.19), homozygote model (OR = 1.22, 95% CI: 1.05-1.41), heterozygote model (OR = 1.21, 95% CI: 1.07-1.36), and dominant model (OR = 1.21, 95% CI: 1.08-1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.
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Metaloproteinase 8 da Matriz/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Genéticos , Grupos Raciais/etnologiaRESUMO
INTRODUCTION: Avian pathogenicEscherichia coli (APEC) causes serious colibacillosis and significant economic losses. Data on profiles of virulence factors and antibiotic resistances among APEC strains are crucial to the control of infection. In this study, strains were isolated from eastern China, and the prevalence of virulence factors and distribution of antibiotic resistance were determined. MATERIAL AND METHODS: APEC strains were isolated and characterised by PCR for O serogroups, virulence factor genes, antibiotic resistance, and phylogenetic groups. RESULTS: O78 was the most prevalent serogroup and type A was the most frequent phylogenetic group. ThefimH,feoB, andiron genes were the most prevalent among the isolates. All isolates were multiresistant, and all strains were resistant to ampicillin and tetracycline, which are widely used in the poultry industry in China. CONCLUSION: This study provided important data on the presence of virulence genes and antibiotic resistance profiles of APEC from poultry farms in eastern China.
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Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response in vitro. Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4+ T cells and CD8+ T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8+ T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.