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1.
Osteoporos Int ; 35(6): 1007-1017, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38430243

RESUMEN

The study, using data from Chongqing, China, and employing Mendelian randomization along with bioinformatics, establishes a causal link between asthma and osteoporosis, beyond glucocorticoid effects. Asthma may contribute to osteoporosis by accelerating bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to osteoporosis. INTRODUCTION: Asthma and osteoporosis are prevalent health conditions with substantial public health implications. However, their potential interplay and the underlying mechanisms have not been fully elucidated. Previous research has primarily focused on the impact of glucocorticoids on osteoporosis, often overlooking the role of asthma itself. METHODS: We conducted a multi-stage stratified random sampling in Chongqing, China and excluded individuals with a history of glucocorticoid use. Participants underwent comprehensive health examinations, and their clinical data, including asthma status, were recorded. Logistic regression and Mendelian randomization were employed to investigate the causal link between asthma and osteoporosis. Furthermore, bioinformatics analyses and serum biomarker assessments were conducted to explore potential mechanistic pathways. RESULTS: We found a significant association between asthma and osteoporosis, suggesting a potential causal link. Mendelian Randomization analysis provided further support for this causal link. Bioinformatics analyses revealed that several molecular pathways might mediate the impact of asthma on bone health. Serum alkaline phosphatase levels were significantly elevated in the asthma group, suggesting potential involvement in bone turnover. CONCLUSION: Our study confirms a causal link between asthma and osteoporosis and highlights the importance of considering asthma in osteoporosis prediction models. It also suggests that asthma may accelerate osteoporosis by increasing bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to bone loss.


Asunto(s)
Asma , Biología Computacional , Análisis de la Aleatorización Mendeliana , Osteoporosis , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Asma/genética , Asma/fisiopatología , Asma/epidemiología , Osteoporosis/genética , Osteoporosis/etiología , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Femenino , Persona de Mediana Edad , Biología Computacional/métodos , Masculino , Estudios Transversales , Anciano , Remodelación Ósea/fisiología , Remodelación Ósea/genética , Adulto , Biomarcadores/sangre , Polimorfismo de Nucleótido Simple , China/epidemiología , Predisposición Genética a la Enfermedad , Osteoclastos , Densidad Ósea/genética , Densidad Ósea/fisiología
2.
Cell Commun Signal ; 22(1): 352, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970078

RESUMEN

BACKGROUND: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism. METHODS: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1. RESULTS: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.


Asunto(s)
Muerte Celular Inmunogénica , Proteínas de la Membrana , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/inmunología , Animales , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Femenino , Ratones , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Línea Celular Tumoral , Ratones Endogámicos BALB C , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo
3.
Physiol Plant ; 176(2): e14254, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38499939

RESUMEN

Together with rice, weeds strive for nutrients and space in farmland, resulting in reduced rice yield and quality. Planting herbicide-resistant rice varieties is one of the effective ways to control weeds. In recent years, a series of breakthroughs have been made to generate herbicide-resistant germplasm, especially the emergence of biotechnological tools such as gene editing, which provides an inherent advantage for the knock-out or knock-in of the desired genes. In order to develop herbicide-resistant rice germplasm resources, gene manipulation has been conducted to enhance the herbicide tolerance of rice varieties through the utilization of techniques such as physical and chemical mutagenesis, as well as genome editing. Based on the current research and persisting problems in rice paddy fields, research on the generation of herbicide-resistant rice still needs to explore genetic mechanisms, stacking multiple resistant genes in a single genotype, and transgene-free genome editing using the CRISPR system. Current rapidly developing gene editing technologies can be used to mutate herbicide target genes, enabling targeted genes to maintain their biological functions, and reducing the binding ability of target gene encoded proteins to corresponding herbicides, ultimately resulting in herbicide-resistant crops. In this review article, we have summarized the utilization of conventional and modern approaches to develop herbicide-resistant cultivars in rice as an effective strategy for weed control in paddy fields, and discussed the technology and research directions for creating herbicide-resistant rice in the future.


Asunto(s)
Herbicidas , Oryza , Oryza/genética , Herbicidas/farmacología , Malezas , Biotecnología , Productos Agrícolas/genética , Resistencia a los Herbicidas/genética
4.
Artículo en Inglés | MEDLINE | ID: mdl-38400848

RESUMEN

PURPOSE: Doxorubicin (Dox) is clinically limited due to its dose-dependent cardiotoxicity. Andrographolide (Andro) has been confirmed to exert cardiovascular protective activities. This study aimed to investigate protective effects of Andro in Dox-induced cardiotoxicity (DIC). METHODS: The cardiotoxicity models were induced by Dox in vitro and in vivo. The viability and apoptosis of H9c2 cells and the myocardial function of c57BL/6 mice were accessed with and without Andro pretreatment. Network pharmacology and RNA-seq were employed to explore the mechanism of Andro in DIC. The protein levels of Bax, Bcl2, NLRP3, Caspase-1 p20, and IL-1ß were qualified as well. RESULTS: In vitro, Dox facilitated the downregulation of cell viability and upregulation of cell apoptosis, after Andro pretreatment, the above symptoms were remarkably reversed. In vivo, Andro could alleviate Dox-induced cardiac dysfunction and apoptosis, manifesting elevation of LVPWs, LVPWd, EF% and FS%, suppression of CK, CK-MB, c-Tnl and LDH, and inhibition of TUNEL-positive cells. Using network pharmacology, we collected and visualized 108 co-targets of Andro and DIC, which were associated with apoptosis, PI3K-AKT signaling pathway, and others. RNA-seq identified 276 differentially expressed genes, which were enriched in response to oxidative stress, protein phosphorylation, and others. Both network pharmacology and RNA-seq analysis identified Tap1 and Timp1 as key targets of Andro in DIC. RT-QPCR validation confirmed that the mRNA levels of Tap1 and Timp1 were consistent with the sequenced results. Moreover, the high expression of NLRP3, Caspase-1 p20, and IL-1ß in the Dox group was reduced by Andro. CONCLUSIONS: Andro could attenuate DIC through suppression of Tap1 and Timp1 and inhibition of NLRP3 inflammasome activation, serving as a promising cardioprotective drug.

5.
Parasitol Res ; 123(1): 108, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38263530

RESUMEN

Enterocytozoon bieneusi and Blastocystis may cause diarrhea in humans and various animals. However, little information is available regarding the prevalence and genetic diversity of E. bieneusi and Blastocystis in donkeys. To fill this gap, we molecularly assessed E. bieneusi and Blastocystis in fecal samples from donkeys (n = 815) in Shanxi Province, north China. The overall prevalence of E. bieneusi and Blastocystis in donkeys was 8.1% and 0.2%, respectively. Region and age were risk factors associated with E. bieneusi infection in donkeys. Three internal transcribed spacer (ITS) genotypes of E. bieneusi were identified in the current study, including two previously described genotypes (D and Henan-IV) and one novel genotype (named SXD1). Of which, genotype D was found to be the most prevalent. Phylogenetic analysis demonstrated that the three genotypes belonged to group 1, implying a potential of zoonotic transmission. Multilocus sequence typing showed that 19, 15, 13, and 22 types were identified at the loci MS1, MS3, MS4, and MS7, respectively, forming six multilocus genotypes (MLGs) distributed in the genotype D. One Blastocystis subtype (ST33) was identified, which has previously been reported only in horses. This is the first molecular-based description of E. bieneusi and Blastocystis infections in donkeys in Shanxi Province, north China, contributing to a better understanding of transmission dynamics and molecular epidemiological characteristics of the two intestinal protozoa.


Asunto(s)
Blastocystis , Enterocytozoon , Humanos , Caballos , Animales , Equidae , Filogenia , Prevalencia , China , Genotipo
6.
Phytochem Anal ; 35(2): 336-349, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37787024

RESUMEN

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.


Asunto(s)
Bupleurum , Espectrometría de Masas en Tándem , Ratones , Animales , Pez Cebra , Cromatografía Líquida de Alta Presión , Bupleurum/química , Células RAW 264.7 , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/análisis , Inflamación/tratamiento farmacológico , Componentes Aéreos de las Plantas/química
7.
Int Wound J ; 21(3): e14771, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38468369

RESUMEN

This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/genética , Anoicis/genética , Células Endoteliales , Fosfatidilinositol 3-Quinasas , Algoritmos
8.
Small ; 19(44): e2302698, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37415530

RESUMEN

Urea oxidation reaction (UOR), an ideal alternative to oxygen evolution reaction (OER), has received increasing attention for realizing energy-saving H2 production and relieving pollutant degradation. Normally, most studied Ni-based UOR catalysts pre-oxidate to NiOOH and then act as active sites. However, the unpredictable transformation of the catalyst's structure and its dissolution and leaching, may complicate the accuracy of mechanism studies and limit its further applications. Herein, a novel self-supported bimetallic Mo-Ni-C3 N3 S3 coordination polymers (Mo-NT@NF) with strong metal-ligand interactions and different H2 O/urea adsorption energy are prepared, which realize a bidirectional UOR/hydrogen evolution reaction (HER) reaction pathway. A series of Mo-NT@NF is prepared through a one-step mild solvothermal method and their multivalent metal states and HER/UOR performance relationship is evaluated. Combining catalytic kinetics, in situ electrochemical spectroscopic characterization, and density-functional theory (DFT) calculations, a bidirectional catalytic pathway is proposed by N, S-anchored Mo5+ and reconstruction-free Ni3+ sites for catalytic active center of HER and UOR, respectively. The effective anchoring of the metal sites and the fast transfer of the intermediate H* by N and S in the ligand C3 N3 S3 H3 further contribute to the fast kinetic catalysis. Ultimately, the coupled HER||UOR system with Mo-NT@NF as the electrodes can achieve energy-efficient overall-urea electrolysis for H2 production.

9.
Opt Lett ; 48(13): 3531-3534, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37390173

RESUMEN

Position-sensitive detectors (PSDs) based on the lateral photovoltaic effect (LPE) are widely used for precision displacement and angle measurement. However, high temperatures can lead to the thermal decomposition or oxidation of nanomaterials frequently utilized in PSDs, and can ultimately affect the performance. In this study, we present a PSD based on Ag/nanocellulose/Si that maintains a maximum sensitivity of 416.52 mV/mm, even at elevated temperatures. By encapsulating nanosilver in a nanocellulose matrix, the device demonstrates excellent stability and performance over a wide temperature range from 300 to 450 K. Its performance can be comparable to that of room temperature PSDs. An approach that uses nanometals to regulate optical absorption and the local electric field overcomes carrier recombination due to nanocellulose, enabling a breakthrough in sensitivity for organic PSDs. The results indicate that the LPE in this structure is dominated by local surface plasmon resonance, presenting opportunities for expanding optoelectronics in high-temperature industrial environments and monitoring applications. The proposed PSD offers a simple, fast, and cost-effective solution for real-time laser beam monitoring, and its high-temperature stability makes it ideal for a wide range of industrial applications.


Asunto(s)
Electricidad , Nanoestructuras , Resonancia por Plasmón de Superficie
10.
BMC Gastroenterol ; 23(1): 395, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968594

RESUMEN

OBJECTIVE: To explore the histopathological features of glandular atrophy of the lamina propria of gastric mucosa during its occurrence and development. METHOD: We performed detailed histological observation and immunohistochemical examination on the endoscopic biopsy and ESD endoscopic resection specimens of 896 patients with glandular atrophy of the lamina propria of gastric mucosa. The EnVision two-step method was used for immunohistochemical staining, and the slices were incubated with primary antibody CK7, CK20, villin, CDX2, MUC5AC, MUC6, p53 and ki-67. Hematoxylin staining was performed and observed under the microscope and statistically analyzed. RESULTS: In the initial stage of glandular atrophy of the lamina propria, the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands are characterized by roughly normal structure of the glandular structure, increased mesenchyme, and widened space between glands. Subsequently, the gland becomes smaller in volume and less in number, especially at the base, in the gastric glandular part of the gastric unit. The disease at this stage has higher incidence, and occurs more often in the elderly who account for 64.0% (573/896) of our study group. The disease in this stage may exhibit some lesions that are physiologic (age-related degeneration) while others are pathological. Therefore, this condition is called simple glandular atrophy of the lamina propria of the gastric mucosa. When the gastric mucosal epithelium is subjected to infection or repeated infections, chemical stimuli, immune factors, and genetic factors, it can lead to the proliferation and transformation of stem cells in the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands, forming single ducts, multiple ducts, or a proliferation of patchy cells. Then, atypical hyperplasia (intraepithelial neoplasia) presents, finally leading to gastric adenocarcinoma. CONCLUSION: Understanding the histopathological characteristics of glandular atrophy of the lamina propria of gastric mucosa is of great significance in controlling the occurrence and development of gastric cancer.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Anciano , Mucosa Gástrica/patología , Neoplasias Gástricas/patología , Biopsia , Adenocarcinoma/patología , Atrofia/patología
11.
Thromb J ; 21(1): 33, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973680

RESUMEN

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit. CASE PRESENTATION: We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction. CONCLUSION: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

12.
J Insect Sci ; 23(2)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36916276

RESUMEN

Nitrogen, a limiting growth factor in wood-feeding insects, was hypothesized to play a role in the recently discovered behavior of subterranean termites returning to the nest to molt. Coptotermes gestroi (Wasmann) exuviae is approximately 11% N by dry weight, and therefore a potentially rich source of recyclable nitrogen. Exuviae from a C. gestroi colony were marked with immunoglobulin G (IgG) and were fed to two-year-old C. gestroi colonies. IgG-marked exuviae were detected with an enzyme-linked immunosorbent assay. The IgG marker was later detected in every caste and life stage except first-instar larvae (L1). The proportion of individuals positive for the marker varied by caste, with the queens always being positive for the marker. The queens and second-or-higher-instar workers (W2+) had significantly higher concentrations of the marker than the eggs and L1. The trophic path of exuviae includes individuals that directly fed on marked exuviae (workers and possibly second-instar larvae) and individuals that secondarily received marked exuviae through trophallaxis (queens, kings, and soldiers). This study described the trophic path of consumed exuviae and demonstrated its role in the recycling of nitrogen in a subterranean termite. Molting at the central nest may be an efficient means to transfer nitrogen from shed exuviae to recipients and may be a nitrogen recycling behavior conserved from a termite ancestor.


Asunto(s)
Cucarachas , Isópteros , Animales , Óvulo , Larva , Inmunoglobulina G
13.
J Insect Sci ; 23(6)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37952215

RESUMEN

With recent evidence of hybridization events in the field, the phenotypic traits of F1 hybrid colonies of 2 destructive subterranean termite species, Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann) remain to be investigated. In this study, laboratory colonies of 2 conspecific pairings and 2 heterospecific pairings (hybrid F = ♀C. formosanus × ♂C. gestroi, hybrid G = ♀C. gestroi × ♂C. formosanus) were examined in Florida, USA, and in Taiwan. Colony nest architecture for both hybrids displayed disorganized carton materials compared to the defined trabecular carton of both parental species. Soldier head measurements were not a reliable approach for diagnostic purposes, as soldier morphometric traits widely overlapped across all mating combinations, except for hybrid F soldiers displaying abnormally long mandibles. Hybrid F soldiers' mandibles also remained parallel when at rest. However, 4 qualitative morphological differences in soldiers were determined for diagnostic purposes. First, the fontanelle in both hybrids is horizontally ellipsoid whereas subcircular in C. gestroi and trianguliform in C. formosanus. Second, sclerotized striations along the postmental sulcus are present in C. gestroi, absent in C. formosanus, and intermediate in both hybrid soldier types. Third, each lateral margin of the fontanelle is flanked by 2 setae in C. formosanus and both hybrids, while a single seta resides on each side of the fontanelle in C. gestroi. Finally, C. gestroi and hybrid soldiers' heads are characterized by a bulging vertex that is lacking in C. formosanus. Therefore, a combination of these 4 characteristics now allows for soldier identification of hybrid Coptotermes.


Asunto(s)
Cucarachas , Isópteros , Animales , Isópteros/genética , Hibridación Genética , Fenotipo , Florida
14.
Int J Mol Sci ; 24(17)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37686043

RESUMEN

Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , ARN Circular/genética , Neoplasias Pulmonares/genética , Biomarcadores
15.
Hepatology ; 74(5): 2774-2790, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34089528

RESUMEN

BACKGROUND AND AIMS: HSCs and portal fibroblasts (PFs) are the major sources of collagen-producing myofibroblasts during liver fibrosis, depending on different etiologies. However, the mechanisms by which their dynamic gene expression directs the transition from the quiescent to the activated state-as well as their contributions to fibrotic myofibroblasts-remain unclear. Here, we analyze the activation of HSCs and PFs in CCL4 -induced and bile duct ligation-induced fibrosis mouse models, using single-cell RNA sequencing and lineage tracing. APPROACH AND RESULTS: We demonstrate that HSCs, rather than PFs, undergo dramatic transcriptomic changes, with the sequential activation of inflammatory, migrative, and extracellular matrix-producing programs. The data also reveal that HSCs are the exclusive source of myofibroblasts in CCL4 -treated liver, while PFs are the major source of myofibroblasts in early cholestatic liver fibrosis. Single-cell and lineage-tracing analysis also uncovers differential gene-expression features between HSCs and PFs; for example, nitric oxide receptor soluble guanylate cyclase is exclusively expressed in HSCs, but not in PFs. The soluble guanylate cyclase stimulator Riociguat potently reduced liver fibrosis in CCL4 -treated livers but showed no therapeutic efficacy in bile duct ligation livers. CONCLUSIONS: This study provides a transcriptional roadmap for the activation of HSCs during liver fibrosis and yields comprehensive evidence that the differential transcriptomic features of HSCs and PFs, along with their relative contributions to liver fibrosis of different etiologies, should be considered in developing effective antifibrotic therapeutic strategies.


Asunto(s)
Células Estrelladas Hepáticas/inmunología , Cirrosis Hepática Experimental/inmunología , Miofibroblastos/inmunología , Animales , Tetracloruro de Carbono/administración & dosificación , Tetracloruro de Carbono/toxicidad , Linaje de la Célula/inmunología , Células Cultivadas , Regulación de la Expresión Génica/inmunología , Técnicas de Sustitución del Gen , Células Estrelladas Hepáticas/metabolismo , Humanos , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/patología , Masculino , Ratones , Ratones Transgénicos , Cultivo Primario de Células , RNA-Seq , Análisis de la Célula Individual
16.
Pediatr Allergy Immunol ; 33(2): e13744, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35212041

RESUMEN

BACKGROUND: Atopic dermatitis (AD) occurs in exclusively breastfed infants. As fatty acids have some immunomodulatory effect, we aimed to investigate the influence of fatty acid compositions in breast milk (BM) on the development of AD in exclusively breastfed infants. METHODS: We enrolled two- to four-month-old exclusively breastfed infants. The objective SCORing Atopic Dermatitis (objSCORAD) was evaluated. The lipid layer of BM was analyzed by gas chromatography for fatty acid levels. Medical charts were reviewed. RESULTS: Forty-seven AD infants and 47 healthy controls were enrolled. The objSCORAD was 20.5 ± 1.7 (shown as mean ± SEM) in the AD group. The age, sex, parental atopy history, and nutrient intake of mothers were not significantly different between two groups. The palmitate and monounsaturated fatty acid (MUFA) levels in BM positively correlated with objSCORAD, while caprylate, acetate, and short-chain fatty acid (SCFA) levels negatively correlated with objSCORAD (p = .031, .019, .039, .013, .022, respectively). However, the butyrate levels in BM were not significantly different. The caprylate and acetate levels in BM were significantly associated with the presence of infantile AD (p = .021 and .015, respectively) after adjusting for age, sex, parental allergy history, MUFA, palmitate, and SCFA levels in BM. ObjSCORAD in infancy was significantly associated with persistent AD (p = .026) after adjusting for age, sex, parental atopy history, caprylate, palmitate, MUFA, acetate, and SCFA levels in BM. CONCLUSION: Caprylate and acetate levels in BM for exclusively breastfed infants were negatively associated with objSCORAD. Lower caprylate and acetate in BM might be the risk factors for infantile AD, while butyrate in BM was not associated with infantile AD.


Asunto(s)
Dermatitis Atópica , Leche Humana , Acetatos , Lactancia Materna , Caprilatos/análisis , Femenino , Humanos , Lactante
17.
Inorg Chem ; 61(34): 13453-13461, 2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-35969492

RESUMEN

It is a challenge to fabricate atomically dispersed metal clusters in polymeric carbon nitride (PCN) for durable photocatalytic reactions owing to the thermodynamic stability limitation. Herein, atomically dispersed Ru clusters are implanted into the PCN skeleton matrix based on an ionic diffusion and coordination (IDC) strategy, the stability of which is improved owing to the robust Ru-N bonds in the formed RuN4 and RuN3 configurations. Additionally, RuN4 and RuN3 as charge transport bridges between two adjacent melon strands efficaciously conquer hydrogen bond restriction in the skeleton to facilitate the in-plane mobility and separation of charge carriers. Moreover, the synergistic effect of adjacent Ru atoms is triggered on the assembled RuN3-RuN4 and RuN3-RuN3 in the atomically dispersed Ru clusters to significantly decrease hydrogen adsorption energy. As a result, the optimal PCN-Ru photocatalyst achieves nearly 6 times higher than the photocatalytic hydrogen evolution (PHE) rate of the Pt/PCN benchmark and maintains the long-term stable running for 104 h of 26 cycles; its overall PHE performance is far superior to the most of single atoms supported on g-C3N4 photocatalysts reported. The findings here gain new insight into the preparation strategy, structure configuration, and reaction mechanism for atomically dispersed metal clusters supported on PCN, which further stimulates the intensive investigations toward developing more efficient and stable PCN-like photocatalytic materials.

18.
Inorg Chem ; 61(39): 15600-15606, 2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-36134910

RESUMEN

Micro/nanostructure control of heterostructures is still a challenge for achieving high efficiency and selectivity of photocatalytic CO2 conversion. In this work, a new three-dimensiona/two-dimensional (3D/2D) heterostructure is fabricated by encapsulating RuS2 nanospheres in the interlayer of mesoporous polymeric carbon nitride (PCN) nanosheets based on an in situ growth and polymerization strategy. The unique microstructure of the obtained 3D/2D RuS2/PCN heterojunction can effectively improve the transfer and separation efficiency of photogenerated charge carriers, reduce the mass transfer resistance of CO2 toward active sites, and provide a confined reaction space, thus propelling the photocatalytic CO2 reduction to CO with high selectivity. The CO yield over the optimal 5%-RuS2/PCN sample reaches 4.2 and 2.8 times as high as that of single PCN and RuS2 within 4 h, respectively. Furthermore, the plausible charge transfer mechanism and CO2 reduction path are revealed by time-dependent in situ Fourier transform infrared (FT-IR) spectra combined with photophysical, electrochemical, and photoelectrochemical techniques and density functional theory (DFT) calculations. This work develops the microstructural engineering design strategy of PCN-based heterojunctions for selective photocatalytic CO2 fuel conversion.

19.
Biom J ; 64(4): 771-804, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35429054

RESUMEN

With the progressive technology, many medical researches are aimed to develop diagnostic tests that can detect diseases faster and accurately. The assessment of the accuracy of the diagnostic test for classifying two groups is through the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). When a paired design is considered, the sample size determination requires the information about two AUC estimates and the corresponding variance and covariance of two AUC estimators. This paper derives the nonparametric estimators of the variance and covariance of two AUC estimators. The result is used to derive the sample size formula when the paired sample is planned. Since most of the results do not have a closed form, numerical results are provided under various scenarios.


Asunto(s)
Pruebas Diagnósticas de Rutina , Área Bajo la Curva , Curva ROC , Tamaño de la Muestra
20.
Int J Mol Sci ; 23(9)2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35562880

RESUMEN

Schizophrenia is associated with several brain deficits, including abnormalities in visual processes. Neuregulin-1 (Nrg1) is a family of trophic factors containing an epidermal growth factor (EGF)-like domain. It is thought to play a role in neural development and has been linked to neuropsychiatric disorders. Abnormal Nrg1 expression has been observed in schizophrenia in clinical studies. Moreover, in schizophrenia, there is more and more evidence found about pathological changes of the retina regarding structural, neurochemical and physiological parameters. However, mechanisms of these changes are not well known. To investigate this, we analysed the function of the visual system using electroretinography (ERG) and the measurement of visual evoked potentials (VEP) in transgenic mice overexpressing Nrg1 type III of three different ages (12 weeks, 24 weeks and 55 weeks). ERG amplitudes tended to be higher in transgenic mice than in control mice in 12-week old mice, whereas the amplitudes were almost similar in older mice. VEP amplitudes were larger in transgenic mice at all ages, with significant differences at 12 and 55 weeks (p values between 0.003 and 0.036). Latencies in ERG and VEP measurements did not differ considerably between control mice and transgenic mice at any age. Our data show for the first time that overexpression of Nrg1 type III changed visual function in transgenic mice. Overall, this investigation of visual function in transgenic mice may be helpful to understand corresponding changes that occur in schizophrenia, as they may find use as biomarkers for psychiatric disorders as well as a potential tool for diagnosis in psychiatry.


Asunto(s)
Neurregulina-1 , Esquizofrenia , Animales , Encéfalo/metabolismo , Potenciales Evocados Visuales , Ratones , Ratones Transgénicos , Neurregulina-1/genética , Neurregulina-1/metabolismo , Esquizofrenia/metabolismo
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