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1.
J Virol Methods ; 299: 114331, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34648821

RESUMO

Vicia cryptic virus M (VCV-M), a member of the genus Amalgavirus of the family Amalgaviridae, was first identified in 2009 in a Vicia faba Linn. planting in Hangzhou, Zhejiang Province, China. However, there has been no further research on the biological features of VCV-M to date and the viral particles and coat protein (CP) have not been identified. The putative CP of VCV-M was predicted from the viral genomic RNA. In this study, a recombinant version of the putative CP of VCV-M (His-CPVCV-M) was produced and used to prepare a polyclonal antiserum against the His-CPVCV-M. Using this antiserum, a Western blot, an immuno-dot-blot and an enzyme-linked immunosorbent assay were developed for testing field samples of V. faba for the presence of VCV-M. Additionally, a digoxigenin (DIG)-labelled DNA probe-based Northern blot assay was established for VCV-M genome detection in field samples. The results showed that both the serological and nucleic acid assays could accurately and sensitively detect VCV-M in V. faba. This research represented the first confirmed expression of the putative CP of VCV-M in infected V. faba tissues. The serological and nucleic acid assays provided two complementary methods for VCV-M detection which could contribute to seed quality control and production increases of V. faba crops.

2.
Bioact Mater ; 9: 397-410, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820579

RESUMO

Extracellular vesicles (EVs) are increasingly used as delivery vehicles for drugs and bioactive molecules, which usually require intravascular administration. The endothelial cells covering the inner surface of blood vessels are susceptible to the shear stress of blood flow. Few studies demonstrate the interplay of red blood cell-derived EVs (RBCEVs) and endothelial cells. Thus, the phagocytosis of EVs by vascular endothelial cells during blood flow needs to be elucidated. In this study, red blood cell-derived extracellular vesicles (RBCEVs) were constructed to investigate endothelial cell phagocytosis in vitro and animal models. Results showed that low magnitude shear stress including low shear stress (LSS) and oscillatory shear stress (OSS) could promote the uptake of RBCEVs by endothelial cells in vitro. In addition, in zebrafish and mouse models, RBCEVs tend to be internalized by endothelial cells under LSS or OSS. Moreover, RBCEVs are easily engulfed by endothelial cells in atherosclerotic plaques exposed to LSS or OSS. In terms of mechanism, oxidative stress induced by LSS is part of the reason for the increased uptake of endothelial cells. Overall, this study shows that vascular endothelial cells can easily engulf EVs in areas of low magnitude shear stress, which will provide a theoretical basis for the development and utilization of EVs-based nano-drug delivery systems in vivo.

3.
Anim Sci J ; 92(1): e13656, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34734664

RESUMO

Two experiments were conducted to investigate the bacterial community of fresh and ensiled paper mulberry prepared with or without lactic acid bacteria (LAB) inoculants in South China. In Experiment 1, the bacterial community, chemical composition, and fermentation products of paper mulberry were analyzed. The results showed that fresh paper mulberry had high crude protein content, buffering capacity value, and amounts of uncultured bacteria. Ensiled paper mulberry showed poor fermentation with high pH value, ammonia-N content, and butyric acid content. In addition, Enterobacter was the dominant genus in silage, followed by Lactobacillus and Enterococcus. Water-soluble carbohydrates, ammonia-N, propionic acid, pH, and lactic acid (LA) were the main factors affecting bacterial community of silage. In Experiment 2, the BP17 (Lactobacillus plantarum) from natural fermented paper mulberry silage and two commercial inoculants (Silage-help [SH] and Chikuso-1 [CH]) were used as additives. Compared with other treatments, BP17 inoculant decreased (p < 0.05) pH and ammonia-N content and increased (p < 0.05) LA content of silage. Inoculation of BP17 also increased the dominance of desirable Lactobacillus and inhibited the growth of harmful bacteria in silage. These results confirmed that paper mulberry could be ensiled and epiphytic LAB inoculant can improve its fermentation quality.

4.
Chest ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34740593

RESUMO

BACKGROUND: Respiratory and cardiovascular disease (CVD) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. RESEARCH QUESTION: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? STUDY DESIGN AND METHODS: A total of 4,621 participants from CARDIA (Coronary Artery Risk Development in Young Adults) cohort study aged 18-30 were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive exams. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore association of chronic respiratory symptoms with incident CVD and all-cause mortality. RESULTS: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. After multivariable adjustment for demographics, cardiovascular risk factors, smoking and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing 0 versus 3-4 respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. INTERPRETATION: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health.

5.
Mitochondrial DNA B Resour ; 6(11): 3125-3126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746383

RESUMO

Tabernaemontana divaricate is a vulnerable species of Apocynaceae with significant medicinal values. In this study, the complete chloroplast (cp) genome of T. divaricate was determined through the Illumina NovaSeq platform. The circular molecular genome was157,954 bp in length with two inverted repeats (IRa and IRb) regions of 25,769 bp, a large single-copy (LSC) region of 88,246 bp, and a small single-copy (SSC) region of 18,170 bp. It contained 131 genes, including 86 protein-coding, 37 tRNA, and eight rRNA genes. Phylogenetic analysis showed that T. divaricata exhibited the closest relationship with Catharanthus roseus and Rauvolfia serpentina.

6.
Rep Prog Phys ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753115

RESUMO

Biomolecular recognition usually leads to the formation of binding complexes, often accompanied by large-scale conformational changes. This process is fundamental to biological functions at the molecular and cellular levels. Uncovering the physical mechanisms of biomolecular recognition and quantifying the key biomolecular interactions are vital to understand these functions. The recently developed energy landscape theory has been successful in quantifying recognition processes and revealing the underlying mechanisms. Recent studies have shown that in addition to affinity, specificity is also crucial for biomolecular recognition. The proposed physical concept of intrinsic specificity based on the underlying energy landscape theory provides a practical way to quantify the specificity. Optimization of affinity and specificity can be adopted as a principle to guide the evolution and design of molecular recognition. This approach can also be used in practice for drug discovery using multidimensional screening to identify lead compounds. The energy landscape topography of molecular recognition is important for revealing the underlying flexible binding or binding-folding mechanisms. In this review, we first introduce the energy landscape theory for molecular recognition and then address four critical issues related to biomolecular recognition and conformational dynamics: (1) specificity quantification of molecular recognition; (2) evolution and design in molecular recognition; (3) flexible molecular recognition; (4) chromosome structural dynamics. The results described here and the discussions of the insights gained from the energy landscape topography can provide valuable guidance for further computational and experimental investigations of biomolecular recognition and conformational dynamics.

7.
Biochem Biophys Rep ; 28: 101162, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34761128

RESUMO

Background: Calpains are calcium activated cysteine proteases that play a pivotal role in the pathophysiology of cardiac remodeling. Methods: Here, we performed left anterior descending coronary artery ligation in rats as a model for ischemic systolic heart failure and examined the time- and region-specific regulation of calpain-1 and calpain-2 in the left ventricular myocardium. Results: Following anterior wall myocardial infarction, calpain activity was significantly increased restricted to the ischemic anterior area at days 1, 5 and 14. No changes in calpain activity at neither time point were detected in the borderzone and remote posterior area of the left ventricle. Of note, calpain activity in the infarcted anterior myocardium was regulated differentially in the acute vs. subacute and chronic phase. In the acute phase, calpain translocation to the plasma membrane and attenuation of the expression of its endogenous inhibitor, calpastatin, were identified as the driving forces. In the subacute and chronic phase, calpain activity was regulated at the level of protein expression that was shown to be essentially independent of transcriptional activity. Conclusions: We conclude that myocardial infarction leads to a distinct calpain regulation pattern in the left ventricular myocardium that is region specific and time dependent. Considering the results from our previous studies, a spatio-temporal interaction between calpains and calcium dependent natriuretic peptide production in the infarcted myocardium is possible. General significance: Our results shed more light in the differential regulation of calpain activity in the myocardium and might aid in the development of targeted post-infarct and/or heart failure therapeutics.

8.
Front Neurol ; 12: 761006, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764934

RESUMO

The cervical anterior spinal artery (ASA) is a very important artery arising from the intracranial vertebral artery (VA). It can play different roles in endovascular treatment (EVT) of spinal vascular diseases. The current understanding of these roles is incomplete; therefore, we performed this review. We found that cervical ASA can be involved in many spinal vascular diseases, such as arteriovenous fistula (AVF), arteriovenous malformation (AVM), and aneurysm, and can serve as a collateral channel in proximal VA occlusion. In AVF and AVM, when the cervical ASA is involved, it often plays the role of an accomplice or victim because it acts as the feeder or as a bystander that does not provide blood flow to the AVF and AVM. In cervical ASA aneurysm, the ASA is a victim. During EVT of VA aneurysms or stenoses, the cervical ASA ostia can be covered or occluded, resulting in ASA ischemia. In this situation, the ASA is a victim. In VA occlusion or the subclavian steal phenomenon, the cervical ASA can serve as a collateral channel to provide blood flow to the posterior circulation. In this case, the ASA plays the role of a friend. According to the role of the cervical ASA in spinal vascular diseases, EVT should be determined "case by case." Most importantly, when EVT is performed to treat these diseases, the cervical ASA axis must be preserved. Therefore, understanding the role of the cervical ASA in spinal vascular diseases is crucial.

9.
Cell Rep ; 37(6): 109974, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758313

RESUMO

The mechanisms of Myc-driven liver tumorigenesis are inadequately understood. Herein we show that Myc-driven hepatocellular carcinoma (HCC) is dramatically aggravated in mice with hepatocyte-specific Ptpn11/Shp2 deletion. However, Myc-induced tumors develop selectively from the rare Shp2-positive hepatocytes in Shp2-deficent liver, and Myc-driven oncogenesis depends on an intact Ras-Erk signaling promoted by Shp2 to sustain Myc stability. Despite a stringent requirement of Shp2 cell autonomously, Shp2 deletion induces an immunosuppressive environment, resulting in defective clearance of tumor-initiating cells and aggressive tumor progression. The basal Wnt/ß-catenin signaling is upregulated in Shp2-deficient liver, which is further augmented by Myc transfection. Ablating Ctnnb1 suppresses Myc-induced HCC in Shp2-deficient livers, revealing an essential role of ß-catenin. Consistently, Myc overexpression and CTNNB1 mutations are frequently co-detected in HCC patients with poor prognosis. These data elucidate complex mechanisms of liver tumorigenesis driven by cell-intrinsic oncogenic signaling in cooperation with a tumor-promoting microenvironment generated by disrupting the specific oncogenic pathway.

10.
J Clin Lab Anal ; : e24135, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799879

RESUMO

OBJECTIVE: The aim of the study was to construct and validate a robust prognostic model based on liquid-liquid phase separation (LLPS)-related genes in lung squamous cell carcinoma (LUSC). METHODS: The Cancer Genome Atlas dataset was used as the discovery set to identify the LLPS-related differentially expressed genes (DEGs) between LUSC and normal tissue. These DEGs were screened by the LASSO Cox regression analysis to identify the genes with nonzero coefficient, which were next included in the multivariate Cox regression analysis to construct the prediction model. The dataset GSE41271 was adopted as the validation set to verify the efficacy of the model. Enrichment analysis and the CIBERSORT were performed to illustrate potential immune mechanisms underlying the prediction model. RESULTS: A total of 48 LLPS-related genes were aberrantly expressed in LUSC. Among them, 7 genes were selected by the LASSO Cox regression analysis to construct the prediction model. Risk index (RI) was calculated according to the model for each patient. The prognosis was significantly different between the patients with high and low RI in the discovery set and the validation set (p < 0.001 and p = 0.028, respectively). The multivariate survival analysis confirmed RI as an independent prognostic factor in LUSC (in the discovery set: p < 0.001, HR = 2.643, 95% CI = 1.986-3.518; in the validation set: p = 0.042, HR = 2.144, 95% CI = 1.026-4.480). A series of pathways involving immune cells were found to be related to RI. The distribution pattern of immune cells and chemokines varied according to the value of RI. CONCLUSION: The prediction model based on LLPS-related genes was constructed and validated as a robust prognostic tool for LUSC using multiple datasets. LLPS might have an impact on LUSC through immune pathways.

11.
Ann Transl Med ; 9(20): 1523, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790729

RESUMO

Background: Lung squamous cell carcinoma (LUSC) approximately accounts for a third of lung cancers. However, the role of N6-methyladenosine (m6A) in LUSC remains largely unknown according to previous studies. Methods: In this study, we investigated the mutations, copy number variants (CNVs), expression of 20 m6A RNA methylation regulators, and clinical data from The Cancer Genome Atlas-LUSC (TCGA-LUSC). These data were used for the training cohort of screening potential biomarkers. The prognostic model of m6A RNA methylation regulators was constructed. A receiver operating characteristic (ROC) analysis was undertaken to determine the area under the curves (AUCs) (for 3- and 5-year survival) for the model. Additionally, the accuracy of the two-gene model was confirmed with external data verifications. Combined two-gene model and clinincal information were performed to construct a nomogram to predict patient's prognostic risk assessment. Results: Fat mass- and obesity-associated protein (FTO) and methyltransferase-like 3 (METTL3) were identified as potential prognostic biomarkers to evaluate benign and malignant tumors and prognosticate. The following prognostic model of m6A RNA methylation regulators was constructed: risk score = 0.162 × FTO - 0.069 × METTL3. Patients in low-risk group [median overall survival (mOS), 43.4 months] had longer survival than those with high-risk (mOS, 67.3 months) with P=0.0023. The smoking grade and risk score could be independent prognostic factors (P=0.00098 and P=0.0014, respectively). Ultimately, a nomogram was developed to assist clinicians to predict clinical outcomes. Conclusions: FTO and METTL3 are potential prognostic biomarkers of LUSC. The two-gene model's use of prognostic risk scores may provide guidance in the selection of therapeutic strategies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34797581

RESUMO

Li-CO2 batteries are explored as promising power systems to alleviate environmental issues and to implement space applications. However, sluggish cathode kinetics of CO2 reduction/evolution result in low round-trip efficiency and poor cycling stability of the fabricated energy-storage devices. Herein, we design a heterostructued photocathode comprising carbon nanotube and carbon nitride to accelerate cathode reactions of a Li-CO2 battery under illumination. Benefiting from the unique defective structure of carbon nitride and favorable interfacial charge transfer, the photocathode effectively harvests ultraviolet-visible light to generate abundant photoexcited carriers and coordinates energetic photoelectrons/holes to participate in the discharge/charge reactions, leading to efficient photo-energy utilization in decreasing reaction barriers and enhancing thermodynamic reversibility of Li-CO2 battery. The resulting battery delivers high round-trip efficiency of 98.8% (ultralow voltage hysteresis of 0.04 V) and superior cycling stability (86.1% efficiency retention after 100 cycles).

13.
BMC Musculoskelet Disord ; 22(1): 940, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758790

RESUMO

BACKGROUND: Simultaneous bilateral distal tibial tubercle high tibial osteotomy (SBDTT-HTO) can result in increased blood loss. The aim of this study is to evaluate the actual hemostatic effect of different tranexamic acid (TXA) treatment regimen in SBDTT-HTO. METHODS: We conducted a retrospective case-control study including 54 patients who underwent SBDTT-HTO. The single-dose group (n = 18) received 1 g of intravenous TXA 15-30 min before surgery, the two-dose group (n = 18) received an additional 1 g of intravenous TXA 6 h after surgery, and the multiple-dose group (n = 18) received an additional 1 g intravenous TXA per-day until discharge. Blood loss, hemoglobin levels, occurrence of any adverse events,functional analysis, quality of life, and pain assessmentswere compared among the three groups. RESULTS: The total blood loss, hidden blood loss, drainage volumes, and haemoglobin level in the multiple-dose group all occupy a significant advantage.(p < 0.05). In addition, better quality of life were observed in patients belonging to the multiple-dose group then single-dose group.(p < 0.05). CONCLUSIONS: Based on our results, for patients undergoing SBDTT-HTO, sequential intravenous TXA administration can effectively and safely reduce blood loss,maintain postoperative Hb levels,and with the advantage of accelerating recovery.


Assuntos
Antifibrinolíticos , Ácido Tranexâmico , Administração Intravenosa , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Estudos de Casos e Controles , Humanos , Osteotomia , Hemorragia Pós-Operatória/prevenção & controle , Qualidade de Vida , Estudos Retrospectivos
14.
Biosens Bioelectron ; 197: 113778, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34798500

RESUMO

The rapid and accurate bacterial testing is a critical step for the management of infectious diseases, but challenges remain largely due to a lack of advanced sensing tools. Here we report the development of highly plasmon-active, biofunctional nanoparticle arrays for simultaneous capture, identification, and differentiation of bacteria by surface-enhanced Raman scattering (SERS). The nanoarrays were facilely prepared through an electrostatic mechanism-controlled self-assembly of metallic nanoparticles at liquid-liquid interfaces, and exhibited high SERS sensitivity beyond femtomole, good reproducibility (relative standard deviation of 2.7%) and stability. Modification of the nanoarrays with concanavalin A allowed to effective capture of both Gram-positive and Gram-negative bacteria (bacterial-capture efficiency maintained beyond 50%) at bacterial concentrations ranging from 50 to 2000 CFU mL-1, as determined by the plate-counting method. Moreover, single-cell Raman fingerprinting and discrimination of eight different bacteria species with high signal-to-noise ratio, excellent spectral reproducibility, and a total assay time of 1.5 h was achieved under fairly mild conditions (24 µW, acquisition time: 1 s). Collectively, we believe that our biofunctionalized, SERS-based self-assembled nanoarrays have great potential to help in rapid and label-free bacterial diagnosis and phenotyping study.

15.
Bioresour Technol ; : 126317, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780911

RESUMO

Haematococcus pluvialis is traditionally cultivated in a suspension for astaxanthin production. This study presents the novel cultivation approach by immobilized H. pluvialis in bacterial cellulose (BC) produced from the symbiosis of Gluconacetobacter xylinus and H. pluvialis. It was observed that the immobilization itself was a regulator to increase the astaxanthin content. The key genes associated to astaxanthin synthesis, such as psy, lcy, bkt, chy, were significantly up-regulated after immobilization. BC immobilized gel can be utilized concurrently with different technologies to improve astaxanthin accumulation (e.g., amount of induction medium, area of biogel, et al). A small-scale screen panel photobioreactor was design to explore the application of the cultivation approach. Compared to suspended culture, the induction time was shortened from 7 days to 3 days. Astaxanthin productivity of red stage reached 343.2 mg·m-2·d-1. This was greater than that of many other cultivation systems.

16.
Rev Assoc Med Bras (1992) ; 67(9): 1251-1255, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34816916

RESUMO

OBJECTIVE: To investigate the associations of high-mobility group box 1 and its specific receptor, receptor for advanced glycation end products with acute lung injury in patients with acute aortic dissection. METHODS: A total of 96 acute aortic dissection patients were divided into acute aortic dissection with acute lung injury group (38 cases) and acute aortic dissection without acute lung injury group (58 cases), according to partial pressure of oxygen/fraction of inspired oxygen. In addition, 44 healthy individuals were selected for the control group. The blood samples were taken. The serum high-mobility group box 1 and receptor for advanced glycation end products levels were detected by enzyme-linked immunosorbent assay, and the partial pressure of oxygen/fraction of inspired oxygen was measured. RESULTS: 24 h after admission, the high-mobility group box 1 and receptor for advanced glycation end products levels in acute aortic dissection with acute lung injury and acute aortic dissection without acute lung injury groups were significantly higher than those in the control group, respectively (p<0.05), and each index in acute aortic dissection with acute lung injury group was significantly higher than that in acute aortic dissection without acute lung injury group (p<0.05). At each time point within 96 h after admission, compared with acute aortic dissection without acute lung injury group, in acute aortic dissection with acute lung injury group, the high-mobility group box 1 and receptor for advanced glycation end products levels were increased, respectively, and the partial pressure of oxygen/fraction of inspired oxygen was decreased. The correlation analysis showed that, in acute aortic dissection patients, the high-mobility group box 1 and receptor for advanced glycation end products levels were negatively correlated with partial pressure of oxygen/fraction of inspired oxygen, respectively (p<0.05). CONCLUSIONS: The serum high-mobility group box 1 and receptor for advanced glycation end products levels may be associated with the occurrence of acute lung injury in acute aortic dissection patients. Monitoring the high-mobility group box 1 and receptor for advanced glycation end products levels can evaluate the risk of acute aortic dissection with acute lung injury.


Assuntos
Lesão Pulmonar Aguda , Aneurisma Dissecante , Proteína HMGB1 , Lesão Pulmonar Aguda/etiologia , Produtos Finais de Glicação Avançada , Humanos , Receptor para Produtos Finais de Glicação Avançada
17.
Front Chem ; 9: 754832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820356

RESUMO

Cannabidiol (CBD) is one specific kind of the cannabinoid in Cannabis sativa L with a wide range of pharmacological activities. However, the poor water solubility and specificity of CBD limits its application in pharmaceutical field. For solving these problems, in this work, we successfully prepared a targeted carrier by grafting biotin (BIO) onto ethylenediamine-ß-Cyclodextrin (EN-CD) in a single step to generate a functionalized supramolecule, named BIO-CD. Subsequently, an amantadine-conjugated cannabinoids (AD-CBD) was prepared and self-assembled with the BIO-CD. A series of methods were used to characterize the inclusion behavior and physicochemical properties of AD-CBD and BIO-CD. The results showed that AD-CBD entered the cavity of BIO-CD and formed a 1:1 host-guest inclusion complex. MTT assay and confocal laser scanning microscopy (CLSM) revealed that the targeting effect and anticancer activity of AD-CBD/BIO-CD inclusion complex against three human cancer cell lines were higher than BIO-CD, AD-CBD and free CBD. Moreover, the inclusion complex could release drugs under weakly acidic conditions. These results demonstrated that AD-CBD/BIO-CD inclusion complex possess excellent targeted and anticancer activity, which is hopeful to be applied in clinic as a new therapeutic approach.

18.
Transl Androl Urol ; 10(10): 3837-3851, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804826

RESUMO

Background: The interferon-inducible transmembrane (IFITM) proteins are localized in the endolysosomal and plasma membranes, conferring cellular immunity to various infections. However, the relationship with carcinogenesis remains poorly elucidated. In the present study, we investigated the role of IFITM in kidney renal clear cell carcinoma (KIRC). Methods: We utilized the online databases of Oncomine, UALCAN and Human Protein Atlas to analyze the expression of IFITMs and validate their levels in human KIRC cells by qPCR and western blot. Furthermore, we evaluated prognostic significance with the Gene Expression Profiling Interactive Analysis tool (Kaplan-Meier (KM) Plotter) and delineated the immune cell infiltration profile related to IFITMs with the TIMER2.0 database. Results: IFITMs were overexpressed in KIRC and varied in subtypes and tumor grades. High expression of IFITMs indicated a poor prognosis and more immune cell infiltration, especially endothelial cells and cancer-associated fibroblasts. IFITMs were associated with immune genes, which correlated with poor prognosis of renal clear cell carcinoma. We also explored the enriched network of IFITMs co-occurrence genes and their targeted transcription factors and miRNA. The expression of IFITMs correlated with hub mutated genes of KIRC. Conclusions: IFITMs play a crucial role in the oncogenesis of KIRC and could be a potential surrogate marker for treatment response to targeted therapies.

19.
J Hepatocell Carcinoma ; 8: 1367-1373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805015

RESUMO

Background: Hepatocellular carcinoma (HCC) is a major cause of liver-related mortality. Serum pentraxin 3 (PTX3) has been revealed to be associated with the development of hepatitis B virus (HBV)-related HCC. This study evaluated whether serum PTX3 is related to the survival of HBV-related HCC patients. Methods: One hundred and seven patients with HBV-related HCC were included. Baseline serum PTX3 levels were quantified using quantitative immunoassay. The HCC patients were followed-up for a median of 24 months and divided into high serum PTX3 level and low PTX3 level groups according to the baseline serum PTX3 levels. The overall survivals of the HBV-related HCC patients according to the serum PTX3 levels were compared. Factors potentially influencing the prognosis of the patients with HBV-related HCC were analyzed. Results: HCC patients with high serum PTX3 levels [PTX3 > 9.25ng/mL (n=85)] had a shorter overall survival time than HCC patients with low serum PTX3 levels [PTX3 ≤ 9.25ng/mL (n=22)] (P = 0.049). HCC patients with serum PTX3 levels between >9.25ng/mL and ≤9.25ng/mL had significant difference in HCC histology grade. Multivariate analysis showed that PTX3 level was an independent risk factor related to the overall survival of HCC patients (hazard ratio: 1.058, 95% confidence interval: 1.031-1.085, P <0.001). Conclusion: These results support the involvement of PTX3 in the disease progression of HCC and suggest the potential of using serum PTX3 levels as a biomarker for the prognostic prediction of HBV-related HCC patients.

20.
Front Bioeng Biotechnol ; 9: 753480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805110

RESUMO

We observed differential infectivity and product yield between two recombinant chimpanzee adenovirus C68 constructs whose primary difference was genome length. To determine a possible reason for this outcome, we characterized the proportion and composition of the empty and packaged capsids. Both analytical ultracentrifugation (AUC) and differential centrifugation sedimentation (DCS, a rapid and quantitative method for measuring adenoviral packaging variants) were employed for an initial assessment of genome packaging and showed multiple species whose abundance deviated between the virus builds but not manufacturing campaigns. Identity of the packaging variants was confirmed by charge detection mass spectrometry (CDMS), the first known application of this technique to analyze adenovirus. The empty and packaged capsid populations were separated via preparative ultracentrifugation and then combined into a series of mixtures. These mixtures showed the oft-utilized denaturing A260 adenoviral particle titer method will underestimate the actual particle titer by as much as three-fold depending on the empty/full ratio. In contrast, liquid chromatography with fluorescence detection proves to be a superior viral particle titer methodology.

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