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1.
Biomed Res Int ; 2021: 6695663, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33937411

RESUMEN

Background: When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing. Materials and Methods: ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31. Results: HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing. Conclusion: Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.

2.
Front Endocrinol (Lausanne) ; 12: 591015, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33841323

RESUMEN

The Delphian lymph node (DLN), also known as the prelaryngeal node, is one component of the central lymph node. The DLN has been well studied in laryngeal cancer, although its significance in papillary thyroid cancer (PTC) remains unclear. We retrospectively analyzed 936 patients with PTC who underwent thyroidectomy by a single surgeon in Tianjin Cancer Hospital from 2017 to 2019. Moreover, 250 PTC patients who underwent thyroidectomy by another surgeon in Tianjin Cancer Hospital from January 2019 to April 2019 were used as a validation cohort. Among the 936 patients with PTC, 581 patients (62.1%) had DLNs, of which 177 samples with metastasis (177/581, 30.5%) were verified. DLN metastasis was significantly correlated with sex, age, tumor size, bilateral cancer, multifocality, extrathyroidal extension, lymphovascular invasion and central and lateral neck lymph node metastasis. Multivariate analysis revealed that independent risk factors for DLN metastasis included age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis, which determined the nomogram. In particular, tumor size was proven to be one of the most predominant single predictors. The diagnostic model had an area under the curve (AUC) of 0.829 (95% confidence interval, 0.804-0.854). The internal and external validations of the nomogram were 0.819 and 0.745, respectively. Our results demonstrate that DLN metastasis appears to be a critical parameter for predicting metastatic disease of the central compartments. Furthermore, this study provides a precise criterion for assessing DLN metastasis and has great clinical significance for treating PTC.

3.
Stem Cell Res Ther ; 12(1): 220, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789742

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. METHOD: A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. RESULT: Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. CONCLUSIONS: The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.

4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(4): 496-501, 2021 Apr 15.
Artículo en Chino | MEDLINE | ID: mdl-33855836

RESUMEN

Objective: To review the clinical research progress of mesenchymal stem cells (MSCs) in the treatment of chronic wounds. Methods: The literature related to the chronic wound repair with MSCs at home and abroad in recent years was extensively reviewed, and the possible mechanism of MSCs in the treatment of chronic wounds, as well as its application and existing problems were summarized. Results: MSCs can participate in all aspects of chronic wound healing to promote wound healing, and has shown broad application prospects in clinical trials. MSCs commonly used in clinical research include bone marrow-derived MSCs, adipose-derived tissue MSCs, and umbilical cord-derived MSCs. Conclusion: MSCs treatment is a promising strategy for the chronic wounds, but there are still many problems in its widespread clinical application that require further research.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cordón Umbilical , Cicatrización de Heridas
5.
Phys Chem Chem Phys ; 23(14): 8222-8235, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33875990

RESUMEN

Two-dimensional (2D) transition metal dichalcogenides (TMDs) exhibit enormous potential in the field of optoelectronics. The high performance of TMD materials and optoelectronic devices significantly depends on processes involved in photoelectric conversion, including photo-excitation, relaxation, transportation, and recombination. Remarkably, inevitable defects in materials prolong or shorten the characteristic time of these processes and even bring about new photoelectric conversion channels, namely, the defect-related relaxation pathways of photoexcited carriers tailor the performance of photoelectric applications. In recent years, there have been numerous investigations in exploring the variant transient signals caused by defects in TMDs utilizing ultrafast spectroscopies. They have the capability in providing an accurate and overall representation of ultrafast processes owing to the subtle temporal resolution. The defect-related mechanisms occurring in different time scales (from femtosecond (fs) to microsecond (µs)) play influential roles throughout the relaxation process of photoexcited species. Herein, we review the defect-related relaxation mechanisms of photoexcited species in TMDs according to the time scale utilizing ultrafast spectroscopy techniques. By interpreting and summarizing the defect-related transient signals, we furnish the direction in material design and performance optimization.

6.
Environ Sci Technol ; 55(9): 6449-6458, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33856785

RESUMEN

Clarifying the sources and fates of atmospheric mercury (Hg) in the Antarctic is crucial to understand the global Hg circulation and its impacts on the fragile ecosystem of the Antarctic. Herein, the annual variations in the isotopic compositions of total gaseous Hg (TGM), with 5-22 days of sampling duration for each sample, were presented for the first time to provide isotopic evidence of the sources and environmental processes of gaseous Hg around the Chinese Great Wall Station (GWS) in the western Antarctic. Different from the Arctic tundra and lower latitude areas in the northern hemisphere, positive δ202Hg (0.58 ± 0.21‰, mean ± 1SD) and negative Δ199Hg (-0.30 ± 0.10‰, mean ± 1SD) in TGM at the GWS indicated little impact from the vegetation-air exchange in the Antarctic. Correlations among TGM Δ199Hg, air temperature, and ozone concentrations suggested that enhanced katabatic wind that transported inland air masses to the continental margin elevated TGM Δ199Hg in the austral winter, while the surrounding marine surface emissions controlled by sea-ice dynamics lowered TGM Δ199Hg in the austral summer. The oxidation of Hg(0) might elevate Δ199Hg in TGM during atmospheric Hg depletion events but have little impact on the seasonal variations of atmospheric Hg isotopes. The presented atmospheric Hg isotopes were essential to identify the transport and transformation of atmospheric Hg and further understand Hg cycling in the Antarctic.


Asunto(s)
Contaminantes Atmosféricos , Mercurio , Contaminantes Atmosféricos/análisis , Regiones Antárticas , Ecosistema , Monitoreo del Ambiente , Mercurio/análisis , Viento
7.
Plant Sci ; 307: 110879, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33902847

RESUMEN

Glume hairiness or pubescence that occurs in hexaploid common wheat and its relatives at different ploidy levels is a distinct morphological marker. Current knowledge about the genetic control of wheat glume hairiness is based on study of Hg1 (formerly Hg) on chromosome 1AS. Here, we report characterization of a new locus for hairy glume Hg2 in synthetic hexaploid wheat line CIGM86.944. Hg2 was inherited a dominant allele. Bulked segregant analysis and RNA-sequencing (BSR-Seq) was performed on an F2:3 population from cross CIGM86.944 × Shannong 29 (glabrous glume), which localized Hg2 in a 2.02 cM genetic interval corresponding to ∼1.08 Mb (754,001,564-755,082,433 Mb) on chromosome 2BL in the Chinese Spring reference genome. Gene annotation and expression identified TraesCS2B02 G562300.1 encoding diacylglycerol kinase 5 protein and TraesCS2B02 G561400.1 encoding a wound-responsive family protein as possible candidate genes regulating development of glume hairiness. The identification of Hg2 provides new insights into the genetic control of glume hairiness in wheat.

8.
Photobiomodul Photomed Laser Surg ; 39(5): 311-320, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33872063

RESUMEN

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33920105

RESUMEN

The bioavailability of heavy metals (HMs) in sediments is closely related to the security of the aquatic environment, but their impacts are poorly researched, particularly in karstic rivers. Therefore, Liujiang River Basin was taken as an example in this study. Seven HMs were analyzed to determine the bioavailability and speciations of HMs in sediments. Moreover, the impacts of environmental factors on HMs were identified. The obtained results suggested that HMs in the sediments are all within their permissible exposure limit (PEL), but Cd and Zn are significantly higher than the soil baseline. Most HMs were found to be in a residual fraction, while their exchangeable fraction was found to be in an extremely low ratio. HMs in bioavailable parts are significantly higher than in the exchangeable and carbonate-bound phases but lower than in the non-residual phase, which demonstrated that HM bioavailability is not confined to the exchangeable and carbonate-bound phases. The correlation coefficients commonly decreased with decreasing speciation ratios, which suggested that the overall bioavailability of metals should be determined by speciation ratios instead of speciations themselves. Noteworthily, most HMs in the residual form were found to be significantly correlated with their overall bioavailability, which highlighted the potential bioavailability of residual form. The non-correlations between pH, electrical conductivity (EC), total dissolved solids (TDS), and HM bioavailability suggested that HMs in the carbonate-bound phase are stable and unsusceptible to environmental variations, while the significant correlations between redox potential (Eh), turbidity, organic matter (OM), main grain size (Mz), and HM bioavailability suggested that HMs in the reducible and oxidizable forms are susceptible to environmental fluctuations. Therefore, the variation of HM bioavailability in karstic rivers is largely regulated by their reducible and oxidizable forms instead of their carbonate-bound form.

10.
Microbiol Res ; 248: 126763, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33892241

RESUMEN

Ensuring food security in an environmentally sustainable way is a global challenge. To achieve this agriculture productivity requires increasing by 70 % under increasingly harsh climatic conditions without further damaging the environmental quality (e.g. reduced use of agrochemicals). Most governmental and inter-governmental agencies have highlighted the need for alternative approaches that harness natural resource to address this. Use of beneficial phytomicrobiome, (i.e. microbes intimately associated with plant tissues) is considered as one of the viable solutions to meet the twin challenges of food security and environmental sustainability. A diverse number of important microbes are found in various parts of the plant, i.e. root, shoot, leaf, seed, and flower, which play significant roles in plant health, development and productivity, and could contribute directly to improving the quality and quantity of food production. The phytomicrobiome can also increase productivity via increased resource use efficiency and resilience to biotic and abiotic stresses. In this article, we explore the role of phytomicrobiome in plant health and how functional properties of microbiome can be harnessed to increase agricultural productivity in environmental-friendly approaches. However, significant technical and translation challenges remain such as inconsistency in efficacy of microbial products in field conditions and a lack of tools to manipulate microbiome in situ. We propose pathways that require a system-based approach to realize the potential to phytomicrobiome in contributing towards food security. We suggest if these technical and translation constraints could be systematically addressed, phytomicrobiome can significantly contribute towards the sustainable increase in agriculture productivity and food security.

11.
Theranostics ; 11(12): 5778-5793, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33897881

RESUMEN

Rationale: Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in the gut microbiota and microbial metabolites have been shown to influence the progression of coronary artery disease. However, the critical microbial and metabolomic changes associated with the cardiovascular protective effects of statins in ACS remain elusive. Methods: In the present study, we performed 16S rRNA sequencing and serum metabolomic analysis in 36 ACS patients who had received chronic statin treatment, 67 ACS patients who had not, and 30 healthy volunteers. A follow-up study was conducted. Metagenomic functional prediction of important bacterial taxa was achieved using PICRUSt2. Results: Statins modulated the gut microbiome of ACS patients towards a healthier status, i.e., reducing potentially pathogenic bacteria such as Parabacteroides merdae but increasing beneficial bacteria such as Bifidobacterium longum subsp. longum, Anaerostipes hadrus and Ruminococcus obeum. Moreover, prior chronic statin therapy was associated with improved outcome in ACS patients. Multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes either directly or by mediating metabolites such as fatty acids and prenol lipids. Finally, we discovered that important taxa associated with statins were correlated with fatty acid- and isoprenoid-related pathways that were predicted by PICRUSt2. Conclusions: Our study suggests that statin treatment might benefit ACS patients by modulating the composition and function of the gut microbiome, which might result in improved circulating metabolites and reduced metabolic risk. Our findings provide new insights for understanding the heterogenic roles of statins in ACS patients through host gut microbiota metabolic interactions.

12.
J Int Med Res ; 49(4): 3000605211005975, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33906529

RESUMEN

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

13.
Ecotoxicol Environ Saf ; 214: 112099, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33714139

RESUMEN

Although fish are widely confirmed to be susceptible to heavy metals (HMs) contamination in sediments, this bioconversion haven't been detailed. This is especially the case in karst areas, where HMs are less stably retained in the sediments and are more bioavailable. Therefore, we surveyed representative karst rivers in Liuzhou, China, in order to study the relationship between the speciations of seven HMs in the sediments with their bioaccumulation in wild fish. The results showed that the HMs in sediments are all below their permissible exposure limit (PEL), but Cd and Zn are significantly higher than soil basline. Most HMs are in residual fraction, while their exchangeable fractions are present in extremely low proportions. The concentration of Zn, Cr and Cd in some fish are above their maximum recommended limit (MRL). The concentrations of most of the HMs in the fish are significantly correlated with the levels in the sediments and given the higher correlation coefficients for their carbonate-bound phase, this phase can be seen to play a critical role in HMs bioconversion. However, the presence of this phase in low proportions enables other phases, especially oxidizable form, to play a greater role in HMs bioaccumulation. Apart from Do, HMs in the fish samples are significantly correlated with multiple environmental factors, demonstrating environmental fluctuations can manipulate HMs bioconversion from sediments; however, their significance depend heavily on the proportion of particular species. HMs in reducible and oxidizable fraction are more important in regulating, rather than promoting, their bioconversion during environmental fluctuations. Fluctuations in EC, TDS and pH can increase the impacts of HMs in carbonate-bound fraction on their bioconversion. Given the higher background values of EC and TDS and lower pH values during the monsoon period, careful attention should be paid to the increased bioconversion of HMs in karst rivers during this season.


Asunto(s)
Monitoreo del Ambiente , Peces/fisiología , Metales Pesados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Bioacumulación , China , Sedimentos Geológicos , Metales Pesados/análisis , Medición de Riesgo , Ríos , Estaciones del Año , Suelo , Contaminantes Químicos del Agua/análisis
14.
Int J Exp Pathol ; 102(2): 105-112, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33710702

RESUMEN

The processes of hypertrophic scar formation are extremely complex, and current animal models have limitations in terms of the complete characterization of lesions. An ideal animal model is indispensable for exploring the complex progression of scar formation to elucidate its pathophysiology and to perform therapeutic testing. This study aimed to establish a long-term, consistent and easily testable animal model by injecting anhydrous alcohol into the dorsal trunk dermis of rabbits. The rabbits were injected with different amounts of anhydrous alcohol. Anhydrous alcohol was infiltrated into the subcutaneous and superficial fascia. The optimal amount of anhydrous alcohol was determined by measuring the area and thickness of the scar. The typical model was established by determining the optimum dosage, and then we analysed the histological characteristics and fibrosis-associated protein expression. The dermal scar was generated by treating with 2 ml/kg anhydrous alcohol and displayed histopathologic features that characterize human hypertrophic scarring, including a parallel collagen fibre orientation, dermal and epidermal thickening, broad collagen deposition and the loss of dermal adnexal structures. The expression of fibrotic pan-markers was also enhanced. Moreover, the scar features and duration were compared between the anhydrous alcohol model and the rabbit ear model. Our results show that injecting anhydrous alcohol in the rabbit model thickened the dermal tissue, stimulated dermal fibroproliferation and resulted in hypertrophic scars with protein and histologic features similar to those seen in humans. Taken together, the findings from this study show that our model could be a feasible and useful tool for further research on the pathogenesis of hypertrophic scars.

15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(2): 200-206, 2021 Feb 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33678659

RESUMEN

In recent years, in the absence of venous component, dilated, overlapping, and tortuous arteries forming a mass of arterial loops with a coil-like appearance have been defined as pure arterial malformation (PAM). It is extremely rare, and its etiology and treatment have not yet been fully elucidated. Here, we reported 2 cases of PAM with associated aneurysmal subarachnoid hemorrhage in this paper. Both patients had severe headache as the first symptom. Subarachnoid hemorrhage was found by CT and computed tomography angiography (CTA) and PAM with associated aneurysm was found by digital subtraction angiography (DSA). In view of the distribution of blood and the location of aneurysms, the aneurysm rupture was the most likely to be considered. Based on the involvement of the lesion in the distal blood supply, only the aneurysm was clamped during the operation. It used to be consider that PAM is safety, because of the presentation and natural history of previously reported cases. Through the cases we reported, we have doubted about "the benign natural history" and discussed its treatment. PAM can promote the formation of aneurysms and should be reviewed regularly. The surgical indications for PAM patients with aneurysm formation need to be further clarified. Management of PAM patients with ruptured aneurysm is the same as that of ruptured aneurysm. Whether there are indications needed to treat simple arterial malformations remains to be further elucidated with the multicenter, randomized controlled studies on this disease.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Aneurisma Roto/complicaciones , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/cirugía , Angiografía de Substracción Digital , Angiografía Cerebral , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología
16.
J Am Heart Assoc ; 10(7): e018511, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33719522

RESUMEN

Background Administrative data have limited sensitivity for case finding of atrial fibrillation/atrial flutter (AF/AFL). Linkage with clinical repositories of interpreted ECGs may enhance diagnostic yield of AF/AFL. Methods and Results We retrieved 369 ECGs from the institutional Marquette Universal System for Electrocardiography (MUSE) repository as validation samples, with rhythm coded as AF (n=49), AFL (n=50), or other competing rhythm diagnoses (n=270). With blinded, duplicate review of ECGs as the reference comparison, we compared multiple MUSE coding definitions for identifying AF/AFL. We tested the agreement between MUSE diagnosis and reference comparison, and calculated the sensitivity and specificity. Using a data set linking clinical registries, administrative data, and the MUSE repository (n=11 662), we assessed the incremental diagnostic yield of AF/AFL by incorporating ECG data to administrative data-based algorithms. The agreement between MUSE diagnosis and reference comparison depended on the coding definitions applied, with the Cohen κ ranging from 0.57 to 0.75. Sensitivity ranged from 60.6% to 79.1%, and specificity ranged from 93.2% to 98.0%. A coding definition with AF/AFL appearing in the first 3 ECG statements had the highest sensitivity (79.1%), with little loss of specificity (94.5%). Compared with the algorithms with only administrative data, incorporating ECG data increased the diagnostic yield of preexisting AF/AFL by 14.5% and incident AF/AFL by 7.5% to 16.1%. Conclusions Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive for AF/AFL detection. Inclusion of MUSE ECG data in AF/AFL case identification algorithms can identify cases missed using administrative data-based algorithms alone.

17.
Artículo en Inglés | MEDLINE | ID: mdl-33660298

RESUMEN

Flavonoids are the important secondary metabolites. They are thought to play an important role in plant adaptation to terrestrial environment. However, the downstream branching pathway of flavonoids in bryophytes, which are the most ancient of terrestrial plants, remains unclear. Here, we cloned a flavonoid 3'-hydroxylase gene (PnF3'H) from the Antarctic moss Pohlia nutans and studied its function in plant stress tolerance. The Arabidopsis with overexpressing PnF3'H (AtOE) were constructed. The AtOE plants had more lateral roots and higher activities of antioxidant enzymes than the wild-type plants under oxidative stress. Meanwhile, the gene expression levels of reactive oxygen species (ROS) scavengers (i.e., AtCAT3, AtFeSOD1, and AtCu-ZnSOD3) were upregulated in the AtOE plants, and the transcription levels of ROS producing enzyme genes were significantly downregulated. The AtOE plans showed increased sensitivity to NaCl stress or abscisic acid (ABA) treatment during seed germination and early root development. Furthermore, several stress-resistant genes in the ABA signaling pathway were also downregulated in the AtOE plants when compared with the wild-type plants. These results suggested that PnF3'H participates in regulating the oxidative tolerance and ABA sensitivity to enable P. nutans to adapt to polar environments.

18.
Nature ; 591(7850): 451-457, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33561864

RESUMEN

All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.


Asunto(s)
/tratamiento farmacológico , Citidina/análogos & derivados , Hidroxilaminas/administración & dosificación , Hidroxilaminas/uso terapéutico , Administración Oral , Células Epiteliales Alveolares/inmunología , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/virología , Animales , Quimioprevención , Quirópteros/virología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Citidina/administración & dosificación , Citidina/uso terapéutico , Citocinas/inmunología , Células Epiteliales/virología , Femenino , Xenoinjertos , Humanos , Inmunidad Innata , Interferón Tipo I/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Trasplante de Pulmón , Masculino , Ratones , Profilaxis Posexposición , Profilaxis Pre-Exposición , /patogenicidad , Replicación Viral
19.
Photodiagnosis Photodyn Ther ; 34: 102218, 2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33592329

RESUMEN

BACKGROUND: The improvement of gene therapy provides hope for the treatment of cancer. However, malignant tumor is a multifactorial disease, which remains difficult to be cured with a single therapy. Our previous study reported that mitochondrial genes glioblastoma-amplified sequence (GBAS) plays a role in the development and treatment of oral squamous cell carcinoma (OSCC). The current study focused on building a mitochondrial-targeting drug co-delivery system for combined photodynamic therapy (PDT) and gene therapy. METHODS: 5-aminolevulinic acid (ALA) photosensitizer loaded chitosan (CS) nanoparticles were prepared using ionic crosslinking method, and further synthesized with the GBAS gene plasmid DNA (shGBAS) by electrostatic attraction. We detected the effects of PDT using the co-delivery system (CS-ALA-shGBAS) on cell proliferation and mitochondrial injury by MTT and reactive oxygen species (ROS) assays, respectively. Additionally, a oral cancer Xenograft model of nude mice was built to test its inhibitive effect on the cancerous growth in vivo. RESULTS: A novel nanocomposite, CS-ALA-shGBAS, was found to be spherical structures and had good dispersion, stability and hypotoxicity. Gel retardation assay showed that CS-ALA nanoparticle could synthesize shGBAS at and above Nanoparticle/Plasmid ratios of 1/2. Excitingly, the co-delivery system was suitable for transfected cells and displayed a superior mitochondrially targeted killing effect on OSCC in vitro and in vivo. CONCLUSION: Our study provides evidence that the chitosan-based co-delivery system of ALA-induced protoporphyrin IX (PpIX) photosensitizer and GBAS gene may be a novel mode of combined therapy for OSCC.

20.
Appl Environ Microbiol ; 87(9)2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33608297

RESUMEN

Diseases caused by soilborne fungal pathogens result in significant crop yield losses and quality reduction. Streptomyces albidoflavus strain W68 is effective in controlling several soilborne fungal diseases. To identify antifungal substances critical for biocontrol activity of W68, the genome of W68 was sequenced and a linear chromosome of 6.80 Mb was assembled. A total of 21 secondary metabolite biosynthesis gene clusters (BGCs), accounting for 12.27% of the genome, were identified. Core gene deletion mutants for each of all 8 BGCs for nonribosomal peptide synthetases and polyketide synthases were created. Among them, only the mutant lacking ctg1-5755 (the gene was renamed as fscD W68) in BGC 19, which shares 100% sequence similarity with the BGC for candicidin synthesis, showed obvious reduction in antifungal activity. A pot experiment revealed that biocontrol effects of the ΔfscD W68 mutant in Rhizoctonia rot of cucumber were also significantly compromised relative to W68. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed that W68 but not the ΔfscD W68 mutant can produce candicidin isomers, indicating that the production of candicidin isomers is key for antifungal activity and biocontrol activity of S. albidoflavus W68.IMPORTANCE This study reports that candicidin-like secondary metabolites produced by microbial cells in natural soil environments can effectively control soilborne fungal diseases, revealing a novel mechanism of microbial biocontrol agents. We demonstrated that the main antifungal activity and biocontrol activity of Streptomyces albidoflavus strain W68 are attributable to the production of candicidin isomers, suggesting that gene clusters for candicidin-like compound biosynthesis might be used as molecular markers to screen and breed microbial strains for biocontrol agent development.


Asunto(s)
Agentes de Control Biológico/metabolismo , Candicidina/metabolismo , Cucumis sativus/microbiología , Enfermedades de las Plantas/prevención & control , Rhizoctonia , Streptomyces/metabolismo , Agentes de Control Biológico/química , Candicidina/química , Isomerismo , Familia de Multigenes , Metabolismo Secundario , Microbiología del Suelo , Streptomyces/genética
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