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Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.
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OBJECTIVE: The addition of reinforcement bars is a commonly used method to improve the fabrication trueness of selective laser melting removable partial denture alloy frameworks. However, the effects of different reinforcement bar designs on the trueness of the entire framework remain unclear. This study investigated the trueness of removable partial denture frameworks of pure titanium fabricated by selective laser melting under different reinforcement bar settings. METHOD: A virtual framework was designed based on the Kennedy Class I partially edentulous model using computer-aided design software. Frameworks with different reinforcement bar settings (Ti-A without reinforcement bar, Ti-B with a single horizontal bar joining the lingual bar, Ti-C with two more bars at the anterior region, Ti-D with another horizontal bar at the anterior region, and Ti-E with one more bar at the posterior region, n = 5) were printed using pure titanium powder using a direct metal laser melting machine. The fabricated frameworks were scanned, and their fabrication trueness was compared with the designed virtual framework using one-way ANOVA. RESULTS: The overall mean discrepancies for Ti-A, Ti-B, Ti-C, Ti-D, and Ti-E were 0.111, 0.047, 0.073, 0.068, and 0.047 mm, respectively. For the group of Ti-A set with no reinforcement bars, larger discrepancies were observed compared with the other four groups (P < .05). Groups Ti-B and Ti-E showed better trueness of the RPI clasps, rests, and distal ends (P < .05). CONCLUSIONS: Adding reinforcement bars improved the printing trueness of the pure titanium frameworks, and different settings resulted in various degrees of improvement. Setting a single reinforcement bar to join the lingual bar or an additional reinforcement bar at the distal end significantly enhanced the printing trueness of the RPI clasps, rests, and distal ends.
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OBJECTIVES: To investigate the influence of the 3D printed micro-structured surfaces on the bond strength of zirconia to resin cement. METHODS: Zirconia specimens were divided into five groups based on manufacturing technique and surface preparation: (1) milled zirconia (M group); (2) milled zirconia airborne abraded (MA group); (3) printed zirconia (M group); (4) printed zirconia airborne abraded (PA group); and (5) printed zirconia with micro-structured surface (PM group). The surface morphology, cross-sectional morphology, and elemental composition were observed using a scanning electron microscope (SEM). Surface roughness was measured using a laser scanning confocal microscope (SLCM). Shear bond strength (SBS) was measured using a universal testing machine after bonding resin cement (n = 10). The failure modes of the bonded fracture interfaces were observed and counted using a stereomicroscope and a SEM. In addition, boundary dimensional accuracy (n = 10) and micro-structural dimensional accuracy (n = 20) of printed zirconia specimens with micro-structured surfaces were measured using digital calipers and Fiji software. The crystalline phase changes before and after surface treatment were investigated using X-ray diffractometry. Data was analysed using one-way ANOVA and Tukey HSD post-hoc tests (α = 0.05). RESULT: The surface micro-structures of the PM group had regular morphology and no obvious defects. The surface roughness results showed that the PM group had higher Sa (42.21±1.38 um) and Ra (21.25±1.80 um) values than the other four groups (p < 0.001). The SBS test showed that the bond strength of the PM group reached 11.23 ± 0.66 MPa, which was 55.97% (p < 0.001) higher than that of the P group (7.20 ± 1.14 MPa). The boundary dimensional accuracy of the PM group was proficient (diameter: 99.63 ± 0.31%, thickness: 98.05 ± 1.12%), and the actual fabrication dimensions of the hexagonal micro-structures reached 77.45%-80.01% of the original design. The micro-structured surface did not affect the crystalline phase of zirconia. CONCLUSIONS: The current study illustrates that 3D-printed microstructured surfaces effectively improve the bond strength of zirconia to resin cements. CLINICAL SIGNIFICANCE: With the advantage of 3D printing, this study provides a new idea for improving the bonding properties of zirconia.
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Colagem Dentária , Materiais Dentários , Teste de Materiais , Microscopia Eletrônica de Varredura , Impressão Tridimensional , Cimentos de Resina , Resistência ao Cisalhamento , Propriedades de Superfície , Zircônio , Zircônio/química , Cimentos de Resina/química , Materiais Dentários/química , Humanos , Análise do Estresse Dentário , Microscopia Confocal , Desenho Assistido por Computador , Estresse MecânicoRESUMO
The drug resistance of poultry red mites to chemical acaricides is a global issue in the control of the mites, which presents an ongoing threat to the poultry industry. Though the increased production of detoxification enzymes has been frequently implicated in resistance development, the overexpression mechanism of acaricide-resistant related genes in mites remains unclear. In the present study, it was observed that the transcription factor Cap 'n' Collar isoform-C (CncC) and its partner small muscle aponeurosis fibromatosis (Maf) were highly expressed in resistant strains compared to sensitive strains under the stress of beta-cypermethrin. When the CncC/Maf pathway genes were down-regulated by RNA interference (RNAi), the expression of the ABC transporter genes was down-regulated, leading to a significant increase in the sensitivity of resistant strains to beta-cypermethrin, suggesting that CncC/Maf played a crucial role in mediating the resistance of D.gallinae to beta-cypermethrin by regulating ABC transporters. Furthermore, it was observed that the content of H2O2 and the activities of peroxidase (POD) and catalase (CAT) enzymes were significantly higher in resistant strains after beta-cypermethrin stress, indicating that beta-cypermethrin activates reactive oxygen species (ROS). In ROS scavenger assays, it was found that the expression of CncC/Maf significantly decreased, along with a decrease in the ABC transporter genes. The present study showed that beta-cypermethrin seemed to trigger the outbreak of ROS, subsequently activated the CncC/Maf pathway, as a result induced the ABC transporter-mediated resistance to the drug, shedding more light on the resistance mechanisms of D.gallinae to pyrethroids.
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Acaricidas , Ácaros , Piretrinas , Animais , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Piretrinas/farmacologia , Acaricidas/farmacologia , Ácaros/genética , Transportadores de Cassetes de Ligação de ATP/genéticaRESUMO
The effects of HNK, I5, and I6 on the expression of protein in hippocampus of depressed mice were studied by isobaric tags for relative and absolute quantitation (iTRAQ) to explore the mechanism of their antidepressant action. HNK, I5, and I6 were administered intragastric administration once a day in the morning for 7 days. The drug was subsequently discontinued for 7 days (without any treatment). On the 15th day, mice in each group were given the drug (1.0, 10.0, 30.0 mg/kg) intragastric stimulation and mouse hippocampal tissues were taken to perform iTRAQ to identify differentially expressed proteins, and bioinformatics was used to analyze the functional enrichment of the differentially expressed proteins. Compared with Ctr group, the number of differentially expressed proteins in HNK, I5, and I6 treatment groups was 158, 88, and 105, respectively. The three groups shared 29 differentially expressed proteins. In addition, compared with HNK group, the number of differentially expressed proteins in I5 and I6 groups was 201 and 203, respectively. A total of 47 and 56 differentially expressed proteins were co-expressed in I5 and I6 groups. Bioinformatics analysis showed that these differentially expressed proteins mainly had the functions of binding, biocatalysis, and transport, and mainly participated in cellular process, biological regulation process, biological metabolism process, and stress reaction process. GO and KEGG pathway analysis found that these differentially expressed proteins were involved long-term potentiation, G13 pathway, platelet activation pathway, and MAPK signaling pathway. HNK, I5, and I6 antidepressants are closely related to sudden stress sensitivity, stress resistance, neurotransmitter, and metabolic pathways. This study provides a scientific basis to further elucidate the mechanism and clinical application of HNK, I5, and I6 antidepressants.
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Ketamina , Proteômica , Camundongos , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Ketamina/farmacologia , Transdução de SinaisRESUMO
STATEMENT OF PROBLEM: The use of intraoral scanners (IOSs) correlates with clinical outcome and patient satisfaction. While the accuracy of IOSs has been well evaluated, studies on the effect of scanning duration on data accuracy are limited. PURPOSE: The purpose of this in vitro study was to investigate the relationship between different scanning durations and the accuracy of the scanned data. MATERIAL AND METHODS: Two experienced operators used the same intraoral scanner (TRIOS 3; 3Shape A/S) to scan a gypsum cast, but with 5 different scanning durations (30 seconds, 60 seconds, 90 seconds, 120 seconds, and 180 seconds), and the trueness of the scanned data was assessed. Ten scans for each duration group were performed, and all the acquired data were evaluated for precision analysis. In addition, each scanned complete arch cast was divided into anterior and posterior regions at the canine teeth, and the 3-way ANOVA test was used to assess the scanning trueness and precision of the scanned anterior and posterior dental arch. RESULTS: The intraoral scanning results between the 2 operators were highly consistent. The data of the 30-second group showed the lowest trueness and precision (P<.001), whereas no significant difference was found among the other groups (P>.05). The trueness and precision of the scanning data in the posterior region was inferior to that in the anterior region (P<.001). CONCLUSIONS: The duration time of the intraoral scanning (ranging from 60 seconds to 180 seconds) did not influence the accuracy of the acquired data, while excessively rapid scanning adversely affected accuracy.
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INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1ß was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1ß release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients.
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Ácido Palmítico , Insuficiência Renal Crônica , Animais , Masculino , Camundongos , Adenina , Caspases/metabolismo , Fibronectinas , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Palmítico/farmacologia , Piroptose , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismoRESUMO
Objectives: Acute kidney injury (AKI) is associated with increased mortality among coronavirus disease 2019 (COVID-19) patients. This meta-analysis aimed to identify risk factors for the development of AKI in patients with COVID-19.Methods: A systematic literature search was conducted in PubMed and EMBASE from 1 December 2019 to 1 January 2023. Due to significant study heterogeneity, meta-analyses were conducted using random-effects models. Meta-regression and sensitivity analysis were also performed.Results: A total of 153,600 COVID-19 patients from 39 studies were included, and 28,003 patients developed AKI. By meta-analysis, we discovered that age, male sex, obesity, black race, invasive ventilation, and the use of diuretics, steroids and vasopressors, in addition to comorbidities such as hypertension, congestive heart failure, chronic kidney disease, acute respiratory distress syndrome, and diabetes, were significant risk factors for COVID-19-associated AKI.Conclusions: Early detection of these risk factors is essential to reduce the incidence of AKI and improve the prognosis of COVID-19 patients.
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Injúria Renal Aguda , COVID-19 , Insuficiência Renal Crônica , Humanos , Masculino , COVID-19/complicações , Fatores de Risco , Prognóstico , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/etiologiaRESUMO
In the life cycle of Dermanyssus gallinae, the embryo is a developmental stage that does not require blood meals, but needs glucose to produce adenosine triphosphate (ATP) through glycolysis or oxidative phosphorylation, providing energy for embryonic development. Glycogen synthase kinase 3 (GSK3), belonging to the serine/threonine kinase family, is a key enzyme involved in glycogen metabolism in many eukaryotes, but not be described in D. gallinae. The present study was conducted to explore the role of Dg-GSK3 in the embryogenesis of D. gallinae. The results of qPCR showed that Dg-GSK3 mRNA was expressed in different development stages of D. gallinae embryos. RNA interference (RNAi) was performed on the female mites and eggs by immersion, and it was found that lowering GSK3 expression level could significantly decrease the female egg laying rate and egg hatching rate (P < 0.05). Some eggs became shrunken and shriveled in appearance. The fecundity of female D. gallinae obtained from the rDg-GSK3-immunized group of chickens (2.56 ± 0.35 eggs per mite, P < 0.0001) decreased significantly from that of the control group (3.49 ± 0.35). The oviposition rate of rDg-GSK3-immunized group (75.94 ± 7.28 %, P = 0.0003ï¼was significantly lower that of the control group (89.69 ± 2.63 %). In conclusion, Dg-GSK3 is a crucial gene during the embryogenesis of D. gallinae, which can affect both the female fecundity and the egg hatching, which help us understand the function of GSK3 gene in the embryogenesis of mites.
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Infestações por Ácaros , Ácaros , Doenças das Aves Domésticas , Animais , Feminino , Infestações por Ácaros/veterinária , Glicogênio Sintase , Quinase 3 da Glicogênio Sintase/genética , Galinhas , Óvulo , Ácaros/genética , Desenvolvimento EmbrionárioRESUMO
l-arabitol is an intermediate of the pentose catabolic pathway in fungi but can also be used as a carbon source by many fungi, suggesting the presence of transporters for this polyol. In this study, an l-arabitol transporter, LatA, was identified in Aspergillus niger. Growth and expression profiles as well as sugar consumption analysis indicated that LatA only imports l-arabitol and is regulated by the arabinanolytic transcriptional activator AraR. Moreover, l-arabitol production from wheat bran was increased in a metabolically engineered A. niger mutant by the deletion of latA, indicating its potential for improving l-arabitol-producing cell factories. Phylogenetic analysis showed that homologs of LatA are widely conserved in fungi.
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Aspergillus niger , Álcoois Açúcares , Aspergillus niger/metabolismo , Filogenia , Álcoois Açúcares/metabolismoRESUMO
Dermanyssus gallinae, also known as the poultry red mite (PRM), is one of widespread ectoparasite in the poultry industry worldwide, causing direct and indirect detriments to poultry as well as substantial financial losses. Novel control methods are urgently needed to improve the current acaricide-based control of D. gallinae. The control approach based on arrestment pheromone is environment-friendly but the related research is limited in PRMs. In the present study we found two compounds from the mite feces acting as arrestment pheromones of D. gallinae, which could lead to mite arrestment upon contact. One is guanine, which was also found in unfed female mites' acid-saline extract. The other is hematin. Moreover, it was found that the ferric ion of hematin played a pivotal role in stimulating the arrestment of mites. Finally, it was found the combination of guanine or/and hematin plus cypermethrin led to significantly improved mite-killing performance compared with cypermethrin, showing a promising potential of novel control method based on the arrestment pheromone.
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Infestações por Ácaros , Ácaros , Doenças das Aves Domésticas , Trombiculidae , Feminino , Animais , Hemina , Aves Domésticas , Controle de Ácaros e Carrapatos , Feromônios/farmacologia , Guanina , Galinhas/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/parasitologia , Infestações por Ácaros/prevenção & controle , Infestações por Ácaros/veterináriaRESUMO
The rarity of circulating tumor cells (CTCs) poses a great challenge to their clinical application as reliable "liquid biopsy" markers for cancer diagnosis. Meanwhile, the epithelial-mesenchymal transition (EMT) led to a reduced efficiency in capturing cells with lost or downregulated epithelial cell adhesion molecule (EpCAM) expressions. In this study, we proposed an integrated, highly efficient strategy for heterogeneous CTC capture and portable detection from the blood of non-small-cell lung cancer (NSCLC) patients. First, the cellulose wrinkled hydrogel with excellent biocompatibility and high specific area was employed as the biointerface to capture heterogeneous CTCs with an improved capture efficiency in virtue of dual targeting against epithelial and mesenchymal ones. Meanwhile, the strategy of glucometer readout was introduced for the quantification of captured CTCs on the same hydrogel interface by a detection probe, Au-G-MSN-Apt, which was fabricated via entrapping glucose into the amino group functionalized mesoporous silica nanoparticle (MSN) framework sealed by l-cysteine modified gold nanoparticles (AuNPs) and then linked with dual aptamers of EpCAM and Vimentin. The number of captured CTCs on the hydrogel could be reflected according to the portable glucose meter (PGM) readings. Moreover, it was found that the captured cells maintained a higher viability on the hydrogel and could be in situ recultured without releasing from the substrate. Finally, this integrated strategy was successfully applied to inspect the correlations between the number of heterogeneous CTCs in the blood of NSCLC patients with disease stage and whether there was distant metastasis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas Metálicas , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Molécula de Adesão da Célula Epitelial/metabolismo , Ouro , Hidrogéis , Oligonucleotídeos , GlucoseRESUMO
This study introduces a customized mask retainer to improve the fit performance of surgical masks using various advanced digital techniques. The participant's 3D face scans with and without a surgical mask were taken by using a smartphone. The mask retainer was designed using the 3D face scan data based on the facial anthropometric landmarks. The fitting was inspected and adjusted using the masked face scan data. The retainer was fabricated using a 3D printer. The effectiveness of the retainer on the augmentation of the fit of the surgical mask was tested according to the Chinese Standard (GB 19083-2010). A questionnaire was used to assess the effect of wearing surgical masks with and without retainers and N95 respirators on subjective perception of discomfort. The effectiveness test of the retainer on the augmentation of the fit performance showed a better than 25-fold increase in the overall fit factor, meeting the fit requirement for KN95 respirators in China. The subjective perception of discomfort of wearing N95 was significantly greater than surgical mask with and without retainers. The fit factor results indicated that by using the retainer, the overall fit factors and that of each exercise significantly increased compared to that of the group with the surgical mask alone. And compared with N95, the surgical mask with the retainer significant improved comfort. The surgical mask with the retainer can provide an alternative of personal protective equipment for healthcare workers.
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Dispositivos de Proteção Respiratória , Humanos , Máscaras , Respiradores N95 , Pessoal de Saúde , Teste de MateriaisRESUMO
Fungi play a critical role in the global carbon cycle by degrading plant polysaccharides to small sugars and metabolizing them as carbon and energy sources. We mapped the well-established sugar metabolic network of Aspergillus niger to five taxonomically distant species (Aspergillus nidulans, Penicillium subrubescens, Trichoderma reesei, Phanerochaete chrysosporium and Dichomitus squalens) using an orthology-based approach. The diversity of sugar metabolism correlates well with the taxonomic distance of the fungi. The pathways are highly conserved between the three studied Eurotiomycetes (A. niger, A. nidulans, P. subrubescens). A higher level of diversity was observed between the T. reesei and A. niger, and even more so for the two Basidiomycetes. These results were confirmed by integrative analysis of transcriptome, proteome and metabolome, as well as growth profiles of the fungi growing on the corresponding sugars. In conclusion, the establishment of sugar pathway models in different fungi revealed the diversity of fungal sugar conversion and provided a valuable resource for the community, which would facilitate rational metabolic engineering of these fungi as microbial cell factories.
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Filamentous fungi produce a wide variety of enzymes in order to efficiently degrade plant cell wall polysaccharides. The production of these enzymes is controlled by transcriptional regulators, which also control the catabolic pathways that convert the released monosaccharides. Two transcriptional regulators, GalX and GalR, control d-galactose utilization in the model filamentous fungus Aspergillus nidulans, while the arabinanolytic regulator AraR regulates l-arabinose catabolism. d-Galactose and l-arabinose are commonly found together in polysaccharides, such as arabinogalactan, xylan and rhamnogalacturonan I. Therefore, the catabolic pathways that convert d-galactose and l-arabinose are often also likely to be active simultaneously. In this study, we investigated the interaction between GalX, GalR and AraR in d-galactose and l-arabinose catabolism. For this, we generated single, double and triple mutants of the three regulators, and analysed their growth and enzyme and gene expression profiles. Our results clearly demonstrated that GalX, GalR and AraR co-regulate d-galactose catabolism in A. nidulans. GalX has a prominent role on the regulation of genes of d-galactose oxido-reductive pathway, while AraR can compensate for the absence of GalR and/or GalX.
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Aspergillus nidulans , Arabinose/metabolismo , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Galactose/metabolismo , Regulação Fúngica da Expressão Gênica , Polissacarídeos/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied. OBJECTIVE: To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis. METHODS: The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein-protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan-Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients. RESULTS: TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.
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The aim of this study was to determine whether carbohydrate antigen 72-4 (CA72-4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72-4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72-4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72-4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72-4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72-4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72-4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72-4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72-4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Albuminas , Albuminúria/urina , Antígenos Glicosídicos Associados a Tumores , Diabetes Mellitus Tipo 2/diagnóstico , HumanosRESUMO
OBJECTIVE: Elucidate the core clinical and genetic characteristics and identify the phenotypic variation between different regions and genotypes of fatal familial insomnia (FFI). METHODS: A worldwide large sample of FFI patients from our case series and literature review diagnosed by genetic testing were collected. The prevalence of clinical symptoms and genetic profile were obtained, and then the phenotypic comparison between Asians versus non-Asians and 129Met/Met versus 129Met/Val were conducted. RESULTS: In total, 131 cases were identified. The age of onset was 47.51±12.53 (range 17-76) years, 106 patients died and disease duration was 13.20±9.04 (range 2-48) months. Insomnia (87.0%) and rapidly progressive dementia (RPD; 83.2%) occurred with the highest frequency. Hypertension (33.6%) was considered to be an objective indicator of autonomic dysfunction. Genotype frequency at codon 129 was Met/Met (84.7%) and Met/Val (15.3%), and allele frequency was Met (92.4%) and Val (7.6%).129 Met was a risk factor (OR: 3.728, 95% CI: 2.194 to 6.333, p=0.000) for FFI in the non-Asian population. Comparison of Asians and non-Asians revealed clinical symptoms and genetic background to show some differences (p<0.05). In the comparison of 129 polymorphisms, a longer disease duration was found in the 129 MV group, with alleviation of some clinical symptoms (p<0.05). After considering survival probability, significant differences in survival time between genotypes remained (p<0.0001). CONCLUSIONS: Insomnia, RPD and hypertension are representative key clinical presentations of FFI. Phenotypic variations in genotypes and geographic regions were documented. Prion protein gene 129 Met was considered to be a risk factor for FFI in the non-Asian population, and 129 polymorphisms could modify survival duration.
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Genótipo , Insônia Familiar Fatal/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Priônicas/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto JovemRESUMO
Xylitol is widely used in the food and pharmaceutical industries as a valuable commodity product. Biotechnological production of xylitol from lignocellulosic biomass by microorganisms is a promising alternative option to chemical synthesis or bioconversion from D-xylose. In this study, four metabolic mutants of Aspergillus niger were constructed and evaluated for xylitol accumulation from D-xylose and lignocellulosic biomass. All mutants had strongly increased xylitol production from pure D-xylose, beechwood xylan, wheat bran and cotton seed hulls compared to the reference strain, but not from several other feed stocks. The triple mutant ΔladAΔxdhAΔsdhA showed the best performance in xylitol production from wheat bran and cotton seed hulls. This study demonstrated the large potential of A. niger for xylitol production directly from lignocellulosic biomass by metabolic engineering.
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Aspergillus niger , Xilitol , Aspergillus niger/genética , Biomassa , Fermentação , Engenharia Metabólica , XiloseRESUMO
As an opportunistic phytopathogen, Sarocladium strictum has only been shown to cause neurological disease in immunocompromised patients, where antifungal therapy was not effective. We report a case of Sarocladium strictum meningoencephalitis in an apparently immunocompetent young woman who presented with severe headache and slight fever after undergoing transnasal endoscopic repair of cerebrospinal fluid rhinorrhea. Chronic sinusitis and suspicious intracranial fungal lesions were observed on enhanced magnetic resonance imaging (MRI). Both culture and metagenomic next-generation sequencing of her cerebrospinal fluid were positive for Sarocladium strictum. After local debridement, treatment with amphotericin B plus voriconazole and Ommaya reservoir implantation, the patient improved significantly. Unfortunately, her symptoms worsened again despite plenty of antifungal therapy for a month.