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BACKGROUND: The risk stratification of pulmonary arterial hypertension proposed by the European Society of Cardiology /European Respiratory Society guidelines in 2015 and 2022 included two to three echocardiographic indicators. However, the specific value of echocardiography in risk stratification of pre-capillary pulmonary hypertension (pcPH) has not been efficiently demonstrated. Given the complex geometry of the right ventricular (RV) and influencing factors of echocardiographic parameter, there is no single echocardiographic parameter that reliably informs about PH status. We hypothesize that a multi-parameter comprehensive index can more accurately evaluate the severity of the pcPH. The purpose of this study was to develop and validate an echocardiographic risk score model to better assist clinical identifying high risk of pcPH during initial diagnosis and follow-up. METHODS: We studied 197 consecutive patients with pcPH. A multivariable echocardiographic model was constructed to predict the high risk of pcPH in the training set. Points were assigned to significant risk factors in the final model based on ß-coefficients. We validated the model internally and externally. RESULTS: The echocardiographic score was constructed by multivariable logistic regression, which showed that pericardial effusion, right atrial (RA) area, RV outflow tract proximal diameter (RVOT-Prox), the velocity time integral of the right ventricular outflow tract (TVIRVOT) and S' were predictors of high risk of pcPH. The area under curve (AUC) of the training set of the scoring model was 0.882 (95%CI: 0.809-0.956, p < 0.0001). External validation was tested in a test dataset of 77 patients. The AUC of the external validation set was 0.852. A 10-point score risk score was generated, with scores ranging from 0 to 10 in the training cohort. The estimate risk of high risk of pcPH ranged from 25.1 to 94.6%. CONCLUSIONS: The echocardiographic risk score using five echocardiographic parameters could be comprehensive and useful to predict the high risk of pcPH for initial assessment and follow-up.
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Valor Predictivo de las Pruebas , Función Ventricular Derecha , Humanos , Masculino , Femenino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Reproducibilidad de los Resultados , Anciano , Estudios Retrospectivos , Pronóstico , Presión Arterial , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Índice de Severidad de la Enfermedad , Adulto , Técnicas de Apoyo para la Decisión , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Ecocardiografía Doppler , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/diagnósticoRESUMEN
Dairy is recognized as a good source of calcium, which is important for preventing osteoporosis. However, the relationship between milk and bone health is more complex than just calcium supplementation. It is unwise to focus solely on observing the effects of a single nutrient. Lactose, proteins, and vitamins in milk, as well as fatty acids, oligosaccharides, and exosomes, all work together with calcium to enhance its bioavailability and utilization efficiency through various mechanisms. We evaluate the roles of dairy nutrients and active ingredients in maintaining bone homeostasis from the perspective of the dairy matrix effects. Special attention is given to threshold effects, synergistic effects, and associations with the gut-bone axis. We also summarize the associations between probiotic/prebiotic milk, low-fat/high-fat milk, lactose-free milk, and fortified milk with a reduced risk of osteoporosis and discuss the potential benefits and controversies of these dairy products. Moreover, we examine the role of dairy products in increasing peak bone mass during adolescence and reducing bone loss in old age. It provides a theoretical reference for the use of dairy products in the accurate prevention and management of osteoporosis and related chronic diseases and offers personalized dietary recommendations for bone health in different populations.
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Productos Lácteos , Leche , Osteoporosis , Osteoporosis/prevención & control , Humanos , Animales , Leche/química , Calcio de la Dieta , Densidad Ósea/efectos de los fármacos , NutrientesRESUMEN
Plant height and heading date are important agronomic traits in wheat (Triticum aestivum L.) that affect final grain yield. In wheat, knowledge of pseudo-response regulator (PRR) genes on agronomic traits is limited. Here, we identify a wheat TaPRR95 gene by genome-wide association study to be associated with plant height. Triple allele mutant plants produced by CRISPR/Cas9 show increased plant height, particularly the peduncle, with an earlier heading date. The longer peduncle is mainly caused by the increased cell elongation at its upper section, whilst the early heading date is accompanied by elevated expression of flowering genes, such as TaFT and TaCO1. A peduncle-specific transcriptome analysis reveals up-regulated photosynthesis genes and down-regulated IAA/Aux genes for auxin signaling in prr95aabbdd plants that may act as a regulatory mechanism to promote robust plant growth. A haplotype analysis identifies a TaPRR95-B haplotype (Hap2) to be closely associated with reduced plant height and increased thousand-grain weight. Moreover, the Hap2 frequency is higher in cultivars than that in landraces, suggesting the artificial selection on the allele during wheat breeding. These findings suggest that TaPRR95 is a regulator for plant height and heading date, thereby providing an important target for wheat yield improvement.
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JASMONATE-ZIM DOMAIN (JAZ) repressor proteins work as co-receptors in the jasmonic acid (JA) signalling pathway and are essential for plant development and environmental adaptation. Despite wheat being one of the main staple food crops, until recently, comprehensive analysis of its JAZ gene family has been limited due to the lack of complete and high-quality reference genomes. Here, using the latest reference genome, we identified 17 JAZ genes in the wheat D-genome donor Aegilops tauschii. Then, 54 TaJAZs were identified in common wheat. A systematic examination of the gene structures, conserved protein domains, and phylogenetic relationships of this gene family was performed. Five new JAZ genes were identified as being derived from tandem duplication after wheat divergence from other species. We integrated RNA-seq data and yield QTL information and found that tandemly duplicated TaJAZ genes were prone to association with spike-related traits. Moreover, 12 TaJAZ genes were located within breeding selection sweeps, including 9 tandemly duplicated ones. Haplotype variation analysis of selected JAZ genes showed significant association of TaJAZ7A and TaJAZ13A with thousand-grain weight. Our work provides a clearer picture of wheat JAZ gene evolution and puts forward the possibility of using these genes for wheat yield improvement.
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Induction of cuproptosis and targeting of multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([CuII(L)Cl] 1 and [CuII2CuI(L)2Cl3] 2, where HL is the (E)-N-methyl-2-(phenyl(pyridin-2-yl)methylene ligand), to assess their antilung cancer activities. Both copper complexes showed better anticancer activity than cisplatin and exhibited hemolysis comparable to that of cisplatin. In vivo experiments showed that complex 2 retarded the A549 cell growth in a mouse xenograft model with low systemic toxicity. Primarily, complex 2 kills lung cancer cells in vitro and in vivo by triggering multiple pathways, including cuproptosis. Complex 2 is the first mixed-valent Cu(I/II) complex to induce cellular events consistent with cuproptosis in cancer cells, which may stimulate the development of mixed-valent copper complexes and provide effective cancer therapy.
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Antineoplásicos , Complejos de Coordinación , Cobre , Neoplasias Pulmonares , Tiosemicarbazonas , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/uso terapéutico , Humanos , Cobre/química , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Ratones , Ratones Desnudos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Células A549 , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Hemólisis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos BALB CRESUMEN
Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.
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Raw milk is the foundation of quality and safety in the dairy industry, and improving milk source management is the fundamental guarantee. Milk-derived exosomes (MDEs) are nanoscale information transfer molecules secreted by mammary cells with unique content and high stability, which can be used not only as potential markers to analyze key traits of lactation, reproduction, nutrition and health of animals, but also help farm managers to take timely interventions to improve animal welfare, milk quality, and functional traits. Our review first outlines the latest advances in MDEs isolation and purification, compositional analysis and characterization tools. We then provide a comprehensive summary of recent applications of MDEs liquid biopsy in breed selection, disease prevention and control, and feeding management. Finally, we evaluate the impact of processing on the stability of MDEs to offer guidance for dairy production and storage. The limitations and challenges in the development and use of MDEs markers are also discussed. As a noninvasive marker with high sensitivity and specificity, the MDEs-mediated assay technology is expected to be a powerful tool for measuring cow health and raw milk quality, enabling dynamic and precise regulation of dairy cows and full traceability of raw milk.
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Non-platinum metal-based complexes have good potential for cancer treatment. Here, we designed and synthesized five hydrazone copper(II) complexes, [Cu2(HL)2Cl2] 1A, [Cu2(HL)2(NO3)H2O]·NO3 2A, [Cu2(HL)2Br2] 3A, [Cu(L)pyridine] 1B and [Cu(HL)(pyridine)Br] 3B, and evaluated their anti-lung cancer activities. MTT experiments revealed that these copper(II) complexes exhibit higher anticancer activity than cisplatin. Mechanism studies revealed that complex 3A induced G1 phase cell cycle arrest, and induced cell apoptosis via reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Scratch wound healing assay was also performed, revealing that complex 3A have good anti-cell migration activity. Hemolysis assays showed good blood biocompatibility of complex 3A. Furthermore, complex 3A can significantly inhibit the proliferation of A549 3D tumor spheroid. An in vivo anticancer study showed that complex 3A could delays the growth of A549 tumor xenografts with lower systemic toxicity. These results highlight the great possibility of developing highly active copper complexes as anti-lung cancer agents.
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Antineoplásicos , Complejos de Coordinación , Neoplasias Pulmonares , Humanos , Cobre/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Modelos Moleculares , Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Piridinas/farmacología , Apoptosis , Línea Celular TumoralRESUMEN
Yak milk is a characteristic animal product of yaks in the Qinghai-Tibet Plateau. Although yak milk production is low, it is richer in nutrients such as protein, fat, and lactose, a more comprehensive range of bioactive components, and unique microbial resources than Holstein cow milk. The plateau environment makes yak milk resistant to hypoxia, anti-fatigue, antioxidant, antibacterial, and relieves chronic diseases. In this paper, based on the systematic analysis of yak milk research results in the past 20 years using CiteSpace 6.1.R2, we reviewed yak lactation performance and nutritional efficacy of yak milk. This paper summarizes the improvement of traditional yak dairy processing technology, and also focuses on the microbial diversity of yak milk sources and their beneficial effects. The purpose of this review is to provide scientific support for the development of a quality yak milk industry on the Tibetan plateau.
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In this study, the effects of freezing yak milk at -20 °C and -40 °C for 30, 90 and 180 days on the fermentation characteristics and storage quality of the corresponding yogurt were discussed. The results showed that, compared with that of yogurt made from fresh yak milk, the lactic acid bacteria (LAB) growth and acid production rate of the yogurt in the -20 °C group decreased at 90 d. The water-holding capacity, viscosity and hardness decreased during storage, and a sour taste was prominent, while no significant changes were observed in the -40 °C group. At 180 d of freezing, the post-acidification of the yogurt in the -20 °C and -40 °C groups increased after 21 d of storage. Compared with the -40 °C group, the -20 °C group showed a significant decrease in LAB counts, a decrease in pH value to 3.63-3.80 and poor texture and sensory quality.
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Obesity has become a global public health problem that seriously affects the quality of life. As an important part of human diet, dairy products contain a large number of nutrients that are essential for maintaining human health, such as proteins, peptides, lipids, vitamins, and minerals. A growing number of epidemiological investigations provide strong evidence on dairy interventions for weight loss in overweight/obese populations. Therefore, this paper outlines the relationship between the consumption of different dairy products and obesity and related metabolic diseases. In addition, we dive into the mechanisms related to the regulation of glucose and lipid metabolism by functional components in dairy products and the interaction with gut microbes. Lastly, the role of dairy products on obesity of children and adolescents is revisited. We conclude that whole dairy products exert more beneficial effect than single milk constituent on alleviating obesity and that dairy matrix has important implications for metabolic health.
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Background: Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term, full-spectrum right ventricular parameters on morphology, pressure and function at certain follow-up time points after PE onset. More exploration of right ventricular function would provide useful clues for long-term management of patients with PE. Methods: For this systematic review and meta-analysis, we completed a literature search in Pubmed, EMBASE and WebofScience (from Jan 1st, 1998 to April 20th, 2023). Studies of patients with acute PE followed-up longer than 3 months with right ventricle assessment and written in English-language were included. Right ventricular function was assessed by either echocardiography or computed tomographic pulmonary angiography (CTPA). The primary outcome was structural and functional parameters of the right ventricle, and the secondary outcomes were functional assessments [New York Heart Association (NYHA) functional classification and 6-min walk test distance (6 MWD)], at each follow-up time points. Random effect meta-analyses were performed using R software (PROSPERO: CRD42023433332). Findings: A total of 33 studies (3920 patients) were included in the final analysis. The 3-month, 6-month and 1-year prevalence of right ventricular dysfunction (RVD) was 0.34 [95% confidence interval (CI) 0.21-0.48, I2 = 96%], 0.26 (95% CI 0.17-0.36, I2 = 93%) and 0.34 (95% CI 0.19-0.48, I2 = 94%), respectively. Pooled tricuspid annulus plane systolic excursion (TAPSE), right ventricular to left ventricular diameter (RV/LV) ratio and pulmonary artery systolic pressure (PASP) at 1-year was 21.80 mm (95% CI 20.08-23.52, I2 = 93%), 0.64 (95% CI 0.48-0.81, I2 = 92%) and 27.33 mmHg (95% CI 18.88-35.78) (I2 = 96%), respectively. The proportion of NYHA III-IV was 0.06 (95% CI 0.0-0.12) and the pooled 6 MWD was 462.98 m (95% CI 447.55-478.41) over 1 year. Patients treated with thrombolysis had lower prevalence of RVD (1-year 0.17 and 0.07 in systemic thrombolysis and catheter-directed thrombolysis, respectively) than those treated with anticoagulation therapy alone (1-year 0.24) but the pooled risk ratio (RR) was not statistically significant. Interpretation: Although the conclusion of this study may be limited by its high heterogeneity from varied study designs, inclusion criteria and definition of RVD of each study, our findings suggested that persistent RVD and functional impairment were of considerable high prevalence during long-term follow-up after acute PE. Treatment strategy may influence the prevalence of long-term RVD. Funding: This study is supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061). The National Key Research and Development Program of China (2016YFC0905600). National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-02-03). CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8).
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Plant breeding is constrained by trade-offs among different agronomic traits by the pleiotropic nature of many genes. Genes that contribute to two or more favourable traits with no penalty on yield are rarely reported, especially in wheat. Here, we describe the editing of a wheat auxin response factor TaARF12 by using CRISPR/Cas9 that rendered shorter plant height with larger spikes. Changes in plant architecture enhanced grain number per spike up to 14.7% with significantly higher thousand-grain weight and up to 11.1% of yield increase under field trials. Weighted Gene Co-Expression Network Analysis (WGCNA) of spatial-temporal transcriptome profiles revealed two hub genes: RhtL1, a DELLA domain-free Rht-1 paralog, which was up-regulated in peduncle, and TaNGR5, an organ size regulator that was up-regulated in rachis, in taarf12 plants. The up-regulation of RhtL1 in peduncle suggested the repression of GA signalling, whereas up-regulation of TaNGR5 in spike may promote GA response, a working model supported by differential expression patterns of GA biogenesis genes in the two tissues. Thus, TaARF12 complemented plant height reduction with larger spikes that gave higher grain yield. Manipulation of TaARF12 may represent a new strategy in trait pyramiding for yield improvement in wheat.
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Edición Génica , Triticum , Triticum/genética , Giberelinas , Fitomejoramiento , Agricultura , Grano Comestible/genéticaRESUMEN
With increasing health awareness worldwide, lactose intolerance has become a major concern of consumers, creating new market opportunities for low-lactose/lactose-free dairy foods. In recent years, through innovating processes and technologies, dairy manufacturers have significantly improved the variety, and functional and sensory qualities of low-lactose and lactose-free dairy products. Based on this, this paper first covers the pathology and epidemiology of lactose intolerance and market trends. Then, we focus on current advantages and disadvantages of different lactose hydrolysis technologies and improvements in these technologies to enhance nutritional value, and functional, sensory, and quality properties of lactose-free dairy products. We found that more and more cutting-edge technologies are being applied to the production of lactose-free dairy products, and that these technologies greatly improve the quality and production efficiency of lactose-free dairy products. Hopefully, our review can provide a theoretical basis for the marketing expansion and consumption guidance for low-lactose/lactose-free dairy products.
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The aim of this study was to prepare conjugates of casein (CA) with pectin (CP) or arabinogalactan (AG) by the Maillard reaction (wet-heating) and to investigate the effects of CP or AG on the structural and functional properties of casein. The results indicated that the highest grafting degree of CA with CP or AG was observed at 90 °C for 1.5 h or 1 h, respectively. Secondary structure showed that grafting with CP or AG reduced the α-helix level and increased the random coil level of CA. Glycosylation treatment of CA-CP and CA-AG exhibited lower surface hydrophobicity and higher absolute ζ-potential values, further significantly improving the functional properties of CA (e.g., solubility, foaming property, emulsifying property, thermal stability, and antioxidant activity). Accordingly, our results indicated that it is feasible for CP or AG to improve the functional properties of CA by the Maillard reaction.
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Reacción de Maillard , Pectinas , Caseínas , GalactanosRESUMEN
Environmental acidification impairs microorganism diversity and their functions on substance transformation. Rhodococcus is a ubiquitously distributed genus for contaminant detoxification in the environment, and it can also adapt a certain range of pH. This work interpreted the acid responses from both phenotype and metabolism in strain Rhodococcus biphenylivorans TG9T (TG9) induced at pH 3. The phenotype alterations were described with the number of culturable and viable cells, intracellular ATP concentrations, cell shape and entocyte, degradation efficiency of polychlorinated biphenyl (PCB) 31 and biphenyl. The number of culturable cells maintained rather stable within the first 10 days, even though the other phenotypes had noticeable alterations, indicating that TG9 possesses certain capacities to survive under acid stress. The metabolism responses were interpreted based on transcription analyses with four treatments including log phase (LP), acid-induced (PER), early recovery after removing acid (RE) and later recovery (REL). With the overview on the expression regulations among the 4 treatments, the RE sample presented more upregulated and less downregulated genes, suggesting that its metabolism was somehow more active after recovering from acid stress. In addition, the response mechanism was interpreted on 10 individual metabolism pathways mainly covering protein modification, antioxidation, antipermeability, H+ consumption, neutralization and extrusion. Furthermore, the transcription variations were verified with RT-qPCR on 8 genes with 24-hr, 48-hr and 72-hr acid treatment. Taken together, TG9 possesses comprehensive metabolism strategies defending against acid stress. Consequently, a model was built to provide an integrate insight to understand the acid resistance/tolerance metabolisms in microorganisms.
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Bifenilos Policlorados , Rhodococcus , Bifenilos Policlorados/toxicidad , Biodegradación Ambiental , Rhodococcus/metabolismo , FenotipoRESUMEN
(E)-ß-ocimene, a ubiquitous monoterpene volatile in plants, is emitted from flowers to attract pollinators and/or from vegetative tissues as part of inducible defenses mediated by complex signaling networks when plants are attacked by insect herbivores. Wild pear species Pyrus betuleafolia used worldwide as rootstock generally displays valuable pest-resistant traits and is a promising genetic resource for pear breeding. In the current study, transcriptional changes in this wild pear species infested with a polyphagous herbivore Spodoptera litura and the underlying molecular mechanisms were fully investigated. A total of 3,118 differentially expressed genes (DEGs) were identified in damaged pear leaf samples. Spodoptera litura larvae infestation activated complex phytohormonal signaling networks in which jasmonic acid, ethylene, brassinosteroids, cytokinin, gibberellic acid and auxin pathways were induced, whereas salicylic acid and abscisic acid pathways were suppressed. All DEGs associated with growth-related photosynthesis were significantly downregulated, whereas most DEGs involved in defense-related early signaling events, transcription factors, green leaf volatiles and volatile terpenes were significantly upregulated. The PbeOCS (GWHGAAYT028729), a putative (E)-ß-ocimene synthase gene, was newly identified in P. betuleafolia transcriptome. The upregulation of PbeOCS in S. litura-infested pear leaves supports a potential role for PbeOCS in herbivore-induced plant defenses. In enzyme-catalyzed reaction, recombinant PbeOCS utilized only geranyl pyrophosphate but not neryl diphosphate, farnesyl pyrophosphate or geranylgeranyl diphosphate as a substrate, producing (E)-ß-ocimene as the major product and a trace amount of (Z)-ß-ocimene. Moreover, as a catalytic product of PbeOCS, (E)-ß-ocimene showed repellent effects on larvae of S. litura in dual-choice bioassays. What is more, (E)-ß-ocimene increased mortalities of larvae in no-choice bioassays. These findings provide an overview of transcriptomic changes in wild pears in response to chewing herbivores and insights into (E)-ß-ocimene biosynthesis in pear plants, which will help elucidate the molecular mechanisms underlying pear-insect interactions.
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BACKGROUND: In precapillary pulmonary hypertension (PH), the incidence of different tricuspid regurgitation (TR) degree is poorly defined. The impact of TR severity on pulmonary artery pressure (PAP) assessment and clinical risk stratification in precapillary PH remains unclear. METHODS: A total of 207 patients diagnosed precapillary PH who underwent right heart catheterization (RHC) and echocardiography within 3 days were included. The severity of TR was graded as trace, mild, moderate and severe. Pearson correlation analysis was performed to evaluate the correlation between systolic PAP by echocardiography (sPAPECHO) and mean PAP by RHC (mPAPRHC) in different TR degree groups. The impact factors on risk stratification of precapillary PH were analyzed by logistic regression analysis. RESULTS: The proportion of None, Trace, Mild, Moderate and Severe TR group was 2.4%, 23.7%, 39.1%, 28.5% and 6.3% respectively. Right atrium (RA) area increased gradually with TR aggravation (p < 0.001). Moderate and Severe TR group had higher N-terminal pro-B-type natriuretic peptide (p < 0.001), right atrial pressure (RAP) (p = 0.018), right ventricular basal diameter (RVD)/left ventricular basal diameter (LVD) ratio (p < 0.001), larger right ventricle (RV) (p < 0.001) and lower tricuspid annular plane systolic excursion (p = 0.006) compared with Trace and Mild group. TR-sPAPECHO in Moderate TR group had the greatest correlation coefficient with mPAPRHC (0.742, p < 0.001) followed by Mild (0.635, p < 0.001) and severe group (0.592, p = 0.033), while there was no correlation in Trace TR group (0.308, p = 0.076). Multivariate logistic regression showed three significant independent echocardiography predictors of high-risk precapillary PH: RVD/LVD ratio (OR = 5.734; 95%CI1.502-21.889, p = 0.011), RA area (OR 1.054; 95% CI 1.004-1.107, p = 0.035) and systolic annular tissue velocity of the lateral tricuspid annulus (S') (OR 0.735, 95% CI 0.569-0.949, p = 0.018). CONCLUSIONS: Precapillary PH was not necessarily accompanied by significant TR. None or Trace TRaccounted for 26% in our population and TR-sPAPECHO was not applicable to estimate PAP in these patients. RVD/LVD ratio, RA area and S' can independently predict the high-risk patients with precapillary PH. TR may play an indirect role in risk stratification by affecting these indicators.
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Hipertensión Pulmonar , Insuficiencia de la Válvula Tricúspide , Humanos , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/epidemiología , Insuficiencia de la Válvula Tricúspide/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/complicaciones , Prevalencia , Ecocardiografía Doppler , EcocardiografíaRESUMEN
L. plantarum 1.0386 repairs intestinal epithelial tight junction injury, and the present study was designed to further explore the role of its postbiotics, including the surface protein (1.0386-Slp), peptidoglycan (1.0386-PG) and exopolysaccharide (1.0386-EPS). The results showed that they all could improve the lipopolysaccharide (LPS)-induced decrease of transepithelial electrical resistance, increase of paracellular permeability, release of inflammatory factors, and disruption of tight junctions in Caco-2 cells, and the repairing effect of 1.0386-Slp was better than those of 1.0386-PG and 1.0386-EPS, and was similar to that of L. plantarum 1.0386. Moreover, either L. plantarum 1.0386 or 1.0386-Slp intervention significantly increased the expression of miR-200c inhibited by LPS, while the miR-200c inhibitor weakened the ability of 1.0386-Slp to promote the expression of tight junction proteins (ZO-1, occludin and claudin-1). Meanwhile, 1.0386-Slp restored the distribution of tight junction proteins and inhibited the increase of NF-κB p65, MLC and pMLC protein expression evoked by LPS. However, the addition of miR-200c inhibitors or mimics weakened or strengthened the down-regulation of MLCK-MLC pathway protein expression by 1.0386-Slp, respectively. In summary, 1.0386-Slp may be the main efficacy component of L. plantarum 1.0386, and miR-200c may be involved in the process of 1.0386-Slp inhibiting the MLCK pathway to repair intestinal epithelial tight junction injury.
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Lactobacillus plantarum , MicroARNs , Humanos , Células CACO-2 , Células Epiteliales , Mucosa Intestinal/metabolismo , Lactobacillus plantarum/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Transducción de Señal , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo , Uniones Estrechas , Cadenas Ligeras de Miosina/genética , Cadenas Ligeras de Miosina/metabolismoRESUMEN
Background: Lung adenocarcinoma (LUAD) is a major type of lung cancer with poor prognosis and low 5-year survival rate, which urgently needs further investigation in order to elucidate its mechanisms completely and discover novel therapeutic targets. C1orf74 is a novel protein with unknown function either in normal cells or cancer cells. The aim of this study is to investigate the expression and function of C1orf74 in LUAD cells. Methods: The expression of C1orf74 in LUAD was analyzed using the LUAD datasets from public databases. The prognostic value of C1orf74 in LUAD was analyzed using Kaplan-Meier Plotter. C1orf74 expression in LUAD cell line A549, H1993 and HCC827 was silenced using small interfering RNA, and then the effects of C1orf74 knockdown on proliferation, migration and invasion of LUAD cells were detected by colony formation assay and Transwell assay, the role of C1orf74 in EGFR/AKT/mTORC1 signaling pathway was examined by Western blot, and the function of C1orf74 in cell cycle was detected by flow cytometry. Results: The results of LUAD clinical data showed that C1orf74 was upregulated in LUAD tissues, and its high expression was associated with poor prognosis. The results from cultured LUAD cells demonstrated that C1orf74 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and autophagy. Moreover, C1orf74 knockdown suppressed EGFR/AKT/mTORC1 signaling in LUAD cells. In conclusion, the present study revealed that C1orf74 is upregulated in LUAD tissues and plays an oncogenic role in LUAD, and that C1orf74 positively regulates cell proliferation and mobility through the EGFR/AKT/mTORC1 signaling pathway in LUAD cells.