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1.
PLoS Pathog ; 20(4): e1012153, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38598555

RESUMEN

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-ß/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-ß/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.


Asunto(s)
Vesículas Extracelulares , Cirrosis Hepática , Schistosoma japonicum , Esquistosomiasis Japónica , Animales , Vesículas Extracelulares/metabolismo , Cirrosis Hepática/parasitología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Esquistosomiasis Japónica/metabolismo , Esquistosomiasis Japónica/parasitología , Esquistosomiasis Japónica/patología , Ratones , Interacciones Huésped-Parásitos/fisiología , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/parasitología , Células Estrelladas Hepáticas/patología , MicroARNs/metabolismo , MicroARNs/genética , Transducción de Señal , Humanos , Proteínas del Helminto/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ratones Endogámicos C57BL
2.
Nat Chem Biol ; 20(7): 835-846, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38287154

RESUMEN

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI. The emergence of PAF and PAF-LPLs in ferroptosis caused the instability of biomembranes and signaled the cell death of neighboring cells. This cascade could be suppressed by PAF-acetylhydrolase (II) (PAFAH2) or by addition of antibodies against PAF. Genetic knockout or pharmacological inhibition of PAFAH2 increased PAF production, augmented synchronized ferroptosis and exacerbated ischemia/reperfusion (I/R)-induced AKI. Notably, intravenous administration of wild-type PAFAH2 protein, but not its enzymatically inactive mutants, prevented synchronized tubular cell death, nephron loss and AKI. Our findings offer an insight into the mechanisms of synchronized ferroptosis and suggest a possibility for the preventive intervention of AKI.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Lesión Renal Aguda/tratamiento farmacológico , Ferroptosis/efectos de los fármacos , Animales , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Activación Plaquetaria/metabolismo , Ratones Noqueados , Humanos , Masculino
3.
Stem Cells ; 42(6): 567-579, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38469899

RESUMEN

Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.


Asunto(s)
Movimiento Celular , Péptidos y Proteínas de Señalización Intercelular , Células Madre Mesenquimatosas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Vía de Señalización Wnt , Proteína Wnt3A , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Movimiento Celular/efectos de los fármacos , Proteína Wnt3A/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Humanos , Animales , beta Catenina/metabolismo , Fosforilación/efectos de los fármacos , Ratones , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética
4.
Mol Med ; 30(1): 64, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760723

RESUMEN

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. METHODS: Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. RESULTS: Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. CONCLUSION: These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.


Asunto(s)
Endometriosis , Glutaminasa , Glutamina , Estabilidad del ARN , ARN Largo no Codificante , Proteínas de Unión al ARN , Femenino , Humanos , Glutaminasa/metabolismo , Glutaminasa/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Endometriosis/metabolismo , Endometriosis/genética , Endometriosis/patología , Glutamina/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proliferación Celular , Adulto , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación de la Expresión Génica , Unión Proteica
5.
Phys Chem Chem Phys ; 26(8): 6638-6645, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38221873

RESUMEN

The photochemical isomerization and nonradiative decay processes of hexafluorobenzene (HFB) were investigated theoretically to gain insights into its photochemical mechanism and the perfluoro effect. A complete mechanistic scheme is presented through the characterization of all the possible minima and transition states of the S0, S1, and S2 states at the CASPT2/6-311G**//CAS(6,7)/6-31G* level. On the S0 potential energy surface, HFB could isomerize to three different products [Dewar-HFB (S0-P1), benzvalene-HFB (S0-P2), and fulvene-HFB (S0-P3)]. Following excitation to the S2 state with the perpendicular π → σ* transition, a chair-type minimum with Cs symmetry was found on the S2 potential energy surface. The adjacent S2/S1 conical intersection was immediately accessible from the S2 minimum. The nature of the S1 state was confirmed to have a π → π* character. Both the S2 and S1 photochemistries of HFB yielded Dewar-HFB via the S1/S0 conical intersection. The regeneration of the S0 state from the S1 and T2 states via intersystem crossing or internal conversion was also revealed.

6.
J Asthma ; : 1-7, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38880950

RESUMEN

OBJECTIVE: To investigate the clinical utility of small airway function indices for early identification of GOLD stage 0 chronic obstructive pulmonary disease (COPD). METHODS: This retrospective study enrolled 137 participants at our institution between January 2017 and December 2018, comprising 40 healthy controls, 46 individuals with GOLD stage 0 COPD, and 51 patients with established COPD. Pulmonary function was assessed using the PowerCube spirometry system (GANSHORN, Germany). Parameters evaluated included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and small airway function indicators. RESULTS: The COPD cohort exhibited significantly lower values across all lung function measures compared to the other two groups, particularly for dynamic lung volume parameters such as FEV1%predicted and FEV1/FVC%. Small airway function indices, including FEV3%predicted, FEF75%predicted, FEF50%predicted, FEF25%predicted, and MMEF%predicted, were markedly decreased in the COPD group (all p-values <0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that MMEF/FVC% and FEV3/FVC% had high diagnostic accuracy for COPD, with MMEF/FVC% exhibiting the optimal sensitivity and specificity. CONCLUSION: Small airway function indices, especially MMEF/FVC%, can serve as effective tools for early identification of GOLD stage 0 COPD. Incorporation of these findings into clinical practice may facilitate early diagnosis and intervention, thereby improving treatment outcomes and patient quality of life.

7.
Intern Med J ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563467

RESUMEN

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

8.
BMC Pulm Med ; 24(1): 199, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654208

RESUMEN

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.


Asunto(s)
Prueba de Esfuerzo , Hipertensión Pulmonar Primaria Familiar , Enfermedad Mixta del Tejido Conjuntivo , Óxido Nítrico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/complicaciones , Biomarcadores/análisis , Biomarcadores/metabolismo , Pruebas de Función Respiratoria , Prueba de Óxido Nítrico Exhalado Fraccionado , Índice de Severidad de la Enfermedad , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Péptido Natriurético Encefálico/metabolismo , China , Anciano
9.
Semin Cancer Biol ; 82: 150-161, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-33631296

RESUMEN

Cancer initiating/ stem cells (CSCs) undergo self-renewal and differentiation that contributes to tumor initiation, recurrence and metastasis in colorectal cancer (CRC). Targeting of colorectal cancer stem cells (CCSCs) holds significant promise in eradicating cancer cells and ultimately curing patients with cancer. In this review, we will introduce the current progress of CCSC studies, including the specific surface markers of CCSCs, the intrinsic signaling pathways that regulate the stemness and differentiation characteristics of CCSCs, and the tumor organoid model for CCSC research. We will focus on how these studies will lead to the progress in targeting specific surface markers or signaling pathways on CCSCs by monoclonal antibodies, or by natural or synthetic compounds, or by immunotherapy. As CSCs are highly heterogeneous and plastic, we suggest that combinatory approaches that target the stemness network may represent an important strategy for eradicating cancers.


Asunto(s)
Neoplasias Colorrectales , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Humanos , Inmunoterapia , Células Madre Neoplásicas/metabolismo
10.
Radiology ; 307(5): e222488, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37191488

RESUMEN

Background Germline mutation in the BMPR2 gene is common in patients with pulmonary arterial hypertension (PAH). However, its association with imaging findings in these patients is, to the knowledge of the authors, unknown. Purpose To characterize distinctive pulmonary vascular abnormalities at CT and pulmonary artery angiography in patients with and without BMPR2 mutation. Materials and Methods In this retrospective study, chest CT scans, pulmonary artery angiograms, and genetic test data were acquired for patients diagnosed with idiopathic PAH (IPAH) or heritable PAH (HPAH) between January 2010 and December 2021. Perivascular halo, neovascularity, centrilobular ground-glass opacity (GGO), and panlobular GGO were evaluated at CT and graded on a four-point severity scale by four independent readers. Clinical characteristics and imaging features between patients with BMPR2 mutation and noncarriers were analyzed using the Kendall rank-order coefficient and the Kruskal-Wallis test. Results This study included 82 patients with BMPR2 mutation (mean age, 38 years ± 15 [SD]; 34 men; 72 patients with IPAH and 10 patients with HPAH) and 193 patients without the mutation, all with IPAH (mean age, 41 years ± 15; 53 men). A total of 115 patients (42%; 115 of 275) had neovascularity, and 56 patients (20%; 56 of 275) had perivascular halo at CT, and so-called frost crystals were observed on pulmonary artery angiograms in 14 of 53 (26%) patients. Compared with patients without BMPR2 mutation, patients with BMPR2 mutation more frequently showed two distinctive radiographic manifestations, perivascular halo and neovascularity (38% [31 of 82] vs 13% [25 of 193] in perivascular halo [P < .001] and 60% [49 of 82] vs 34% [66 of 193] in neovascularity [P < .001], respectively). "Frost crystals" were more frequent in patients with BMPR2 mutation compared with noncarriers (53% [10 of 19] vs 12% [four of 34]; P < .01). Severe perivascular halo frequently coexisted with severe neovascularity in patients with BMPR2 mutation. Conclusion Patients with PAH with BMPR2 mutation showed distinctive features at CT, specifically perivascular halo and neovascularity. This suggested a link between the genetic, pulmonary, and systemic manifestations that underly the pathogenesis of PAH. © RSNA, 2023 Supplemental material is available for this article.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Masculino , Humanos , Adulto , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/genética , Estudios Retrospectivos , Mutación/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética
11.
Small ; 19(36): e2301745, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37156743

RESUMEN

Freshwater scarcity crisis threatens human life and economic security. Collecting water from the fog seems to be an effective method to defuse this crisis. Nonetheless, the existing fog collection methods have the limitations of the low fog collection rate and efficiency because of their gravity-based droplet shedding. Here, the aforementioned limitations are resolved by proposing a new fog collection method based on the self-driven jet phenomenon of the mini fog droplets. A prototype fog collector (PFC) composed of a square container that is filled with water is first designed. Both sides of the PFC are superhydrophobic but covered with superhydrophilic pore array. The mini fog droplets touching the side wall are easily captured and spontaneously and rapidly penetrate into the pores to form jellyfish-like jets, which greatly increases the droplet shedding frequency, guaranteeing a higher fog collection rate and efficiency compared with the existing fog collection methods. Based on this, a more practical super-fast fog collector is finally successfully designed and fabricated which is assembled by several PFCs. This work is hoping to resolve the water crisis in some arid but foggy regions.

12.
Respir Res ; 24(1): 156, 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37312153

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the world's leading causes of death and a major chronic respiratory disease. Aerobic exercise, the cornerstone of pulmonary rehabilitation, improves prognosis of COPD patients; however, few studies have comprehensively examined the changes in RNA transcript levels and the crosstalk between various transcripts in this context. This study identified the expression of RNA transcripts in COPD patients who engaged in aerobic exercise training for 12 weeks, and further constructions of the possible RNAs networks were made. METHODS: Peripheral blood samples for all four COPD patients who benefited from 12 weeks of PR were collected pre- and post-aerobic exercises and evaluated for the expression of mRNA, miRNA, lncRNA, and circRNA with high-throughput RNA sequencing followed by GEO date validation. In addition, enrichment analyses were conducted on different expressed mRNAs. LncRNA-mRNA and circRNA-mRNA coexpression networks, as well as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA competing expression networks (ceRNAs) in COPD were constructed. RESULTS: We identified and analyzed the differentially expressed mRNAs and noncoding RNAs in the peripheral blood of COPD patients' post-exercise. Eighty-six mRNAs, 570 lncRNAs, 8 miRNAs, and 2087 circRNAs were differentially expressed. Direct function enrichment analysis and Gene Set Variation Analysis showed that differentially expressed RNAs(DE-RNAs) correlated with several critical biological processes such as chemotaxis, DNA replication, anti-infection humoral response, oxidative phosphorylation, and immunometabolism, which might affect the progression of COPD. Some DE-RNAs were validated by Geo databases and RT-PCR, and the results were highly correlated with RNA sequencing. We constructed ceRNA networks of DE-RNAs in COPD. CONCLUSIONS: The systematic understanding of the impact of aerobic exercise on COPD was achieved using transcriptomic profiling. This research offers a number of potential candidates for clarifying the regulatory mechanisms that exercise has on COPD, which could ultimately help in understanding the pathophysiology of COPD.


Asunto(s)
MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , ARN Largo no Codificante , Humanos , Proyectos Piloto , Transcriptoma , ARN Circular/genética , ARN Largo no Codificante/genética , MicroARNs/genética , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/terapia , ARN Mensajero/genética , Ejercicio Físico
13.
Vet Res ; 54(1): 116, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049816

RESUMEN

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.


Asunto(s)
Schistosoma japonicum , Esquistosomiasis , Humanos , Femenino , Animales , Schistosoma japonicum/genética , Esquistosomiasis/veterinaria , Inmunoglobulina G , Reproducción , Anexinas/metabolismo
14.
J Cardiovasc Pharmacol ; 82(2): 148-156, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37295072

RESUMEN

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).


Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Ticagrelor/efectos adversos , Aspirina , Inhibidores de Agregación Plaquetaria , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Pueblos del Este de Asia , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Ácido Salicílico/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Resultado del Tratamiento
15.
J Chem Phys ; 159(20)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38010330

RESUMEN

Quantum walks are the quantum counterpart of classical random walks and have various applications in quantum information science. Polar molecules have rich internal energy structure and long coherence time and thus are considered as a promising candidate for quantum information processing. In this paper, we propose a theoretical scheme for implementing discrete-time quantum walks on a circle with dipole-dipole coupled SrO molecules. The states of the walker and the coin are encoded in the pendular states of polar molecules induced by an external electric field. We design the optimal microwave pulses for implementing quantum walks on a four-node circle and a three-node circle by multi-target optimal control theory. To reduce the accumulation of decoherence and improve the fidelity, we successfully realize a step of quantum walk with only one optimal pulse. Moreover, we also encode the walker into a three-level molecular qutrit and a four-level molecular ququart and design the corresponding optimal pulses for quantum walks, which can reduce the number of molecules used. It is found that all the quantum walks on a circle in our scheme can be achieved via optimal control fields with high fidelities. Our results could shed some light on the implementation of discrete-time quantum walks and high-dimensional quantum information processing with polar molecules.

16.
Appl Opt ; 62(11): 2756-2765, 2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37133116

RESUMEN

To evaluate corn quality quickly, the feasibility of near-infrared spectroscopy (NIRS) coupled with chemometrics was analyzed to detect the moisture, oil, protein, and starch content in corn. A backward interval partial least squares (BiPLS)-principal component analysis (PCA)-extreme learning machine (ELM) quantitative analysis model was constructed based on BiPLS in conjunction with PCA and the ELM. The selection of characteristic spectral intervals was accomplished by BiPLS. The best principal components were determined by the prediction residual error sum of squares of Monte Carlo cross validation. In addition, a genetic simulated annealing algorithm was utilized to optimize the parameters of the ELM regression model. The established regression models for moisture, oil, protein, and starch can meet the demand for corn component detection with the prediction determination coefficients of 0.996, 0.990, 0.974, and 0.976; the prediction root means square errors of 0.018, 0.016, 0.067, and 0.109; and the residual prediction deviations of 15.704, 9.741, 6.330, and 6.236, respectively. The results show that the NIRS rapid detection model has higher robustness and accuracy based on the selection of characteristic spectral intervals in conjunction with spectral data dimensionality reduction and nonlinear modeling and can be used as an alternative strategy to detect multiple components in corn rapidly.

17.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37108747

RESUMEN

The 9-cis-epoxycarotenoid dioxygenase (NCED) is a key enzyme for the process of ABA synthesis that plays key roles in a variety of biological processes. In the current investigation, genome-wide identification and comprehensive analysis of the NCED gene family in 'Kuerle Xiangli' (Pyrus sinkiangensis Yu) were conducted using the pear genomic sequence. In total, nineteen members of PbNCED genes were identified from the whole genome of pear, which are not evenly distributed over the scaffolds, and most of which were focussed in the chloroplasts. Sequence analysis of promoters showed many cis-regulatory elements, which presumably responded to phytohormones such as abscisic acid, auxin, etc. Synteny block indicated that the PbNCED genes have experienced strong purifying selection. Multiple sequence alignment demonstrated that these members are highly similar and conserved. In addition, we found that PbNCED genes were differentially expressed in various tissues, and three PbNCED genes (PbNCED1, PbNCED2, and PbNCED13) were differentially expressed in response to exogenous Gibberellin (GA3) and Paclobutrazol (PP333). PbNCED1 and PbNCED13 positively promote ABA synthesis in sepals after GA3 and PP333 treatment, whereas PbNCED2 positively regulated ABA synthesis in ovaries after GA3 treatment, and PbNCED13 positively regulated ABA synthesis in the ovaries after PP333 treatment. This study was the first genome-wide report of the pear NCED gene family, which could improve our understanding of pear NCED proteins and provide a solid foundation for future cloning and functional analyses of this gene family. Meanwhile, our results also give a better understanding of the important genes and regulation pathways related to calyx abscission in 'Kuerle Xiangli'.


Asunto(s)
Dioxigenasas , Pyrus , Giberelinas/farmacología , Pyrus/genética , Pyrus/metabolismo , Dioxigenasas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia
18.
Int J Mol Sci ; 24(18)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37762581

RESUMEN

The aim was to determine whether lipid molecules can be used as potential biomarkers for idiopathic pulmonary arterial hypertension (IPAH), providing important reference value for early diagnosis and treatment. Liquid chromatography-mass spectrometry-based lipidomic assays allow for the simultaneous detection of a large number of lipids. In this study, lipid profiling was performed on plasma samples from 69 IPAH patients and 30 healthy controls to compare the levels of lipid molecules in the 2 groups of patients, and Cox regression analysis was used to identify meaningful metrics, along with receiver operator characteristic curves to assess the ability of the lipid molecules to predict the risk of disease in patients. Among the 14 lipid subclasses tested, 12 lipid levels were significantly higher in IPAH patients than in healthy controls. Free fatty acids (FFA) and monoacylglycerol (MAG) were significantly different between IPAH patients and healthy controls. Logistic regression analysis showed that FFA (OR: 1.239, 95%CI: 1.101, 1.394, p < 0.0001) and MAG (OR: 3.711, 95%CI: 2.214, 6.221, p < 0.001) were independent predictors of IPAH development. Among the lipid subclasses, FFA and MAG have potential as biomarkers for predicting the pathogenesis of IPAH, which may improve the early diagnosis of IPAH.


Asunto(s)
Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/patología , Metabolismo de los Lípidos , Biomarcadores/metabolismo , Lípidos
19.
Molecules ; 28(11)2023 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-37298863

RESUMEN

The persulfate-based advanced oxidation process has been an effective method for refractory organic pollutants' degradation in aqueous phase. Herein, α-MnO2 with nanowire morphology was facially fabricated via a one-step hydrothermal method and successfully activated peroxymonosulfate (PMS) for Rhodamine B (RhB) degradation. Influencing factors, including the hydrothermal parameter, PMS concentration, α-MnO2 dosage, RhB concentration, initial pH, and anions, were systematically investigated. The corresponding reaction kinetics were further fitted by the pseudo-first-order kinetic. The RhB degradation mechanism via α-MnO2 activating PMS was proposed according to a series of quenching experiments and the UV-vis scanning spectrum. Results showed that α-MnO2 could effectively activate PMS to degrade RhB and has good repeatability. The catalytic RhB degradation reaction was accelerated by increasing the catalyst dosage and the PMS concentration. The effective RhB degradation performance can be attributed to the high content of surface hydroxyl groups and the greater reducibility of α-MnO2, and the contribution of different ROS (reactive oxygen species) was 1O2 > O2·- > SO4·- > ·OH.


Asunto(s)
Compuestos de Manganeso , Óxidos , Óxidos/química , Compuestos de Manganeso/química , Cinética , Peróxidos/química
20.
BMC Oral Health ; 23(1): 928, 2023 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-38007495

RESUMEN

BACKGROUND: Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle. METHODS: Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height < 9 mm in the edentulous area were selected. The distances from the mandibular nerve canal to the buccal cortex, the lingual cortex and the alveolar ridge crest were measured by using a combination of software. The angular ranges of the buccal-lingual inclination of simulated trans-IAN implants were measured and three-dimensional finite element models were constructed in the mandibular second molar area according to the differences of the inclination angles. A vertical load (200N) was then applied to analyze the biomechanical conditions of the implant-bone interface during median occlusion. RESULTS: The distance at the second molar from the nerve canal to the buccal cortex, lingual cortex and alveolar crest were 6.861 ± 1.194 mm, 2.843 ± 0.933 mm and 7.944 ± 0.77 mm. Trans-IAN implantation was feasible in 73.33% of patients. The minimum angle and maximum angles of the buccal-lingual inclination of the simulated implant were 19.135 ± 6.721° and 39.282 ± 6.581°. When a vertical static load of 200N was applied, the tensile stress in cortical bone gradually increased with the increase of the implant tilt angle. When the inclination angle reached 30°, the tensile stress (105.9 MPa) exceeded the yield strength (104 MPa) of cortical bone. Compared with the conventional implants, the stress peak value of the vertical ultra-short implant in cortical bone was greater than the stress peak value of the conventional implants at 10°(79.81 MPa) and 20°(82.83 MPa) and was smaller than the stress of the implant at 30°(105.9 MPa) and 40°(107.8 MPa). Therefore, when the bone mass allows, conventional-length implants should be selected whenever possible, and an operative range of the trans-IAN implantation in the mandibular second molar could be retained with an inclination angle of < 30°. CONCLUSIONS: The mandibular nerve canal at the mandibular second molar was obviously biased to the lingual side, which ensured sufficient bone mass at the buccal side. In most patients with severe mandibular atrophy, it was possible to maintain a safe distance from the nerve canal with conventional-length implants via the trans-IAN implantation technique.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Implantes Dentales , Humanos , Análisis de Elementos Finitos , Tomografía Computarizada de Haz Cónico/métodos , Proceso Alveolar/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Diente Molar/diagnóstico por imagen , Nervio Mandibular
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