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1.
Fundam Res ; 4(3): 463-470, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38933216

RESUMO

Bioaerosols are a subset of important airborne particulates that present a substantial human health hazard due to their allergenicity and infectivity. Chemical reactions in atmospheric processes can significantly influence the health hazard presented by bioaerosols; however, few studies have summarized such alterations to bioaerosols and the mechanisms involved. In this paper, we systematically review the chemical modifications of bioaerosols and the impact on their health effects, mainly focusing on the exacerbation of allergic diseases such as asthma, rhinitis, and bronchitis. Oxidation, nitration, and oligomerization induced by hydroxyl radicals, ozone, and nitrogen dioxide are the major chemical modifications affecting bioaerosols, all of which can aggravate allergenicity mainly through immunoglobulin E pathways. Such processes can even interact with climate change including the greenhouse effect, suggesting the importance of bioaerosols in the future implementation of carbon neutralization strategies. In summary, the chemical modification of bioaerosols and the subsequent impact on health hazards indicate that the combined management of both chemical and biological components is required to mitigate the health hazards of particulate air pollution.

2.
J Asthma ; : 1-7, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38880950

RESUMO

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.

4.
J Hypertens ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38860405

RESUMO

OBJECTIVE: Pulmonary hypertension is a severe complication of bronchiectasis, characterized by elevated pulmonary vascular resistance (PVR) and subsequent right heart failure. The association between PVR and mortality in bronchiectasis-associated pulmonary hypertension has not been investigated previously. METHODS: In the present study, a retrospective analysis was conducted on 139 consecutive patients diagnosed with bronchiectasis-associated pulmonary hypertension based on right heart catheterization, enrolled between January 2010 and June 2023. Baseline clinical characteristics and hemodynamic assessment were analyzed. The survival time for each patient was calculated in months from the date of diagnosis until the date of death or, if the patient was still alive, until their last visit. RESULTS: Patients with bronchiectasis-associated pulmonary hypertension exhibited estimated survival rates of 89.5, 70, and 52.9 at 1-year, 3-year, and 5-year intervals respectively, with a median survival time of 67 months. Multivariable Cox regression analysis revealed that increased age [(adjusted hazard ratio per year 1.042, 95% confidence interval (CI) 1.008-1.076, P = 0.015] and elevated PVR (adjusted HR per 1 Wood Units 1.115, 95% CI 1.015-1.224, P = 0.023) were associated with an increased risk of all-cause mortality. In contrast, higher BMI was associated with a decreased risk of all-cause death (adjusted hazard ratio per 1 kg/m2 0.915, 95% CI 0.856-0.979, P = 0.009). Receiver-operating characteristic analyses identified a cutoff value for PVR at 4 Wood Units as predictive for all-cause death within 3 years [area under the curve (AUC) = 0.624; specificity= 87.5%; sensitivity= 35.8%; P < 0.05]. Patients with a PVR greater than 4 Wood Units had a significantly higher risk of all-cause death compared with those with 4 Wood Units or less (adjusted hazard ratio 2.392; 95% CI 1.316-4.349; P = 0.019). Notably, there were no significant differences in age, sex, BMI, WHO functional class, 6-min walk distance, and NT-proBNP levels at baseline between patients categorized as having 4 Wood Units or less or greater than 4 Wood Units for PVR. CONCLUSION: Based on these data, PVR could serve as a discriminative marker for distinguishing between nonsevere pulmonary hypertension (PVR ≤ 4 Wood Units) and severe pulmonary hypertension (PVR > 4 Wood Units). The utilization of a PVR cutoff value of 4.0 Wood Units provides enhanced prognostic capabilities for predicting mortality.

5.
Clin Transl Med ; 14(6): e1702, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38861300

RESUMO

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.


Assuntos
Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/complicações , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Fatores de Risco
6.
Phytomedicine ; 130: 155763, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38820661

RESUMO

BACKGROUND: Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. PURPOSE: We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. METHODS: M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. RESULTS: The levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. CONCLUSION: M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.


Assuntos
Emodina , Metabolismo dos Lipídeos , Macrófagos , Nanocápsulas , Pancreatite , Animais , Emodina/farmacologia , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pancreatite/tratamento farmacológico , Células RAW 264.7 , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Anti-Inflamatórios/farmacologia , Quitosana/farmacologia , Quitosana/química , Camundongos Endogâmicos C57BL , Lipopolissacarídeos , Reprogramação Metabólica
7.
Heliyon ; 10(9): e30189, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726199

RESUMO

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

8.
Mol Med ; 30(1): 64, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760723

RESUMO

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.


Assuntos
Endometriose , Glutaminase , Glutamina , Estabilidade de RNA , RNA Longo não Codificante , Proteínas de Ligação a RNA , Feminino , Humanos , Glutaminase/metabolismo , Glutaminase/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Endometriose/metabolismo , Endometriose/genética , Endometriose/patologia , Glutamina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proliferação de Células , Adulto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica , Ligação Proteica
9.
Int Immunopharmacol ; 134: 112255, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744176

RESUMO

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Modelos Animais de Doenças , Mesalamina , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Colite Ulcerativa/terapia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colite Ulcerativa/induzido quimicamente , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Colo/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Células Cultivadas , Masculino , Proliferação de Células/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico
10.
Nat Commun ; 15(1): 4347, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773146

RESUMO

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Astrócitos , Transtorno Depressivo Maior , Camundongos Knockout , Animais , Astrócitos/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Camundongos , Humanos , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/patologia , Masculino , Feminino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Estresse Psicológico/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Comportamento Animal , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Depressão/metabolismo , Depressão/genética , Adulto , Transmissão Sináptica , Pessoa de Meia-Idade
11.
BMC Pulm Med ; 24(1): 199, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654208

RESUMO

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.


Assuntos
Teste de Esforço , Hipertensão Pulmonar Primária Familiar , Doença Mista do Tecido Conjuntivo , Óxido Nítrico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Doença Mista do Tecido Conjuntivo/complicações , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/complicações , Biomarcadores/análise , Biomarcadores/metabolismo , Testes de Função Respiratória , Teste da Fração de Óxido Nítrico Exalado , Índice de Gravidade de Doença , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/diagnóstico , Peptídeo Natriurético Encefálico/metabolismo , China , Idoso
12.
PLoS Pathog ; 20(4): e1012153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38598555

RESUMO

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.


Assuntos
Vesículas Extracelulares , Cirrose Hepática , Schistosoma japonicum , Esquistossomose Japônica , Animais , Vesículas Extracelulares/metabolismo , Cirrose Hepática/parasitologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/patologia , Camundongos , Interações Hospedeiro-Parasita/fisiologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/parasitologia , Células Estreladas do Fígado/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Transdução de Sinais , Humanos , Proteínas de Helminto/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Camundongos Endogâmicos C57BL
13.
Intern Med J ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563467

RESUMO

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.

14.
Stem Cells ; 42(6): 567-579, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38469899

RESUMO

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.


Assuntos
Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular , Células-Tronco Mesenquimais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Via de Sinalização Wnt , Proteína Wnt3A , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Movimento Celular/efeitos dos fármacos , Proteína Wnt3A/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Humanos , Animais , beta Catenina/metabolismo , Fosforilação/efeitos dos fármacos , Camundongos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética
15.
Front Immunol ; 15: 1345838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449875

RESUMO

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) are present in almost all cancer tissues and play an important role in preserving autoimmune tolerance and tissue homeostasis. The tumor inflammatory microenvironment causes the reprogramming of Tregs, resulting in the conversion of Tregs to immunosuppressive phenotypes. This process ultimately facilitates tumor immune escape or tumor progression. However, current systemic Treg depletion therapies may lead to severe autoimmune toxicity. Therefore, it is crucial to understand the mechanism of Treg reprogramming and develop immunotherapies that selectively target Tregs within tumors. This article provides a comprehensive review of the potential mechanisms involved in Treg cell reprogramming and explores the application of Treg cell immunotherapy. The interference with reprogramming pathways has shown promise in reducing the number of tumor-associated Tregs or impairing their function during immunotherapy, thereby improving anti-tumor immune responses. Furthermore, a deeper understanding of the mechanisms that drive Treg cell reprogramming could reveal new molecular targets for future treatments.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Neoplasias/terapia , Imunoterapia , Imunossupressores , Fenótipo , Microambiente Tumoral
16.
J Am Heart Assoc ; 13(6): e031867, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38497483

RESUMO

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Humanos , Ratos , Animais , Hipertensão Pulmonar/metabolismo , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , RNA Circular/genética , Artéria Pulmonar , Hipóxia/complicações , Proliferação de Células/fisiologia
17.
ISME Commun ; 4(1): ycad015, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38439944

RESUMO

Plants actively recruit microbes from the soil, forming species-specific root microbiomes. However, their relationship with plant adaptations to temperature and precipitation remains unclear. Here we examined the host-selected and conserved microbiomes of 13 native plant species in the Xilingol steppe, Inner Mongolia, a semi-arid region in China. By calculating the global precipitation and temperature niches of these plants, considering plant phylogenetic distances, and analyzing functional traits, we found that these factors significantly influenced the rhizosphere microbiome assembly. We further quantified the strength of host selection and observed that plants with wider precipitation niches exhibited greater host selection strength in their rhizosphere microbiome assembly and higher rhizosphere bacterial diversity. In general, the rhizosphere microbiome showed a stronger link to plant precipitation niches than temperature niches. Haliangium exhibited consistent responsiveness to host characteristics. Our findings offer novel insights into host selection effects and the ecological determinants of wild plant rhizosphere microbiome assembly, with implications for steering root microbiomes of wild plants and understanding plant-microbiome evolution.

18.
Bioengineering (Basel) ; 11(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38534516

RESUMO

The cellular prion protein (PrPc) is a cell surface glycoprotein that is highly expressed in a variety of cancer tissues in addition to the nervous system, and its elevated expression is correlated to poor prognosis in many cancer patients. Our team previously found that patients with colorectal cancer (CRC) with high-level PrPc expression had significantly poorer survival than those with no or low-level PrPc expression. Mouse antibodies for PrPc inhibited tumor initiation and liver metastasis of PrPc-positive human CRC cells in mouse model experiments. PrPc is a candidate target for CRC therapy. In this study, we newly cloned a mouse anti-PrPc antibody (Clone 6) and humanized it, then affinity-matured this antibody using a CHO cell display with a peptide antigen and full-length PrPc, respectively. We obtained two humanized antibody clones with affinities toward a full-length PrPc of about 10- and 100-fold of that of the original antibody. The two humanized antibodies bound to the PrPc displayed significantly better on the cell surface than Clone 6. Used for Western blotting and immunohistochemistry, the humanized antibody with the highest affinity is superior to the two most frequently used commercial antibodies (8H4 and 3F4). The two new antibodies have the potential to be developed as useful reagents for PrPc detection and even therapeutic antibodies targeting PrPc-positive cancers.

19.
Polymers (Basel) ; 16(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38543384

RESUMO

With the vigorous development of the Internet of Things, 5G technology, and artificial intelligence, flexible wearable sensors have received great attention. As a simple and low-cost power supply in wearable sensors, the triboelectric nanogenerator (TENG) has a wide range of applications in the field of flexible electronics. However, most polymers are thermally poor conductors (less than 0.1 W/(m·K)), resulting in insufficient heat dissipation performance and limiting the development of TENG. In this study, a high-performance non-woven fabric TENG with strong thermal conductivity (0.26 W/m·K) was achieved by introducing ZrB2 into the polyurethane (PU) matrix. The excellent output performance with an open circuit voltage (Voc) of 347.6 V, a short circuit current (Isc) of 3.61 µA, and an accumulated charge of 142.4 nC endows it with good sensitivity. The electrospun PU/ZrB2 composites exhibit excellent sensing performance to detect body movements in situ, such as pressing, clapping, running, and walking. Moreover, the generated power can light up 224 LED bulbs as a demonstration of self-powering ability.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 310: 123933, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38309007

RESUMO

Near-infrared spectroscopy (NIRS) is a rapid, nondestructive analytical technique utilized in various fields. However, the NIR data, which consists of hundreds of dimensions, may exhibit considerable duplication in the spectrum information. This redundancy might impair modeling effectiveness. As a result, feature selection on the spectral data becomes critical. The Max-Relevance Min-Redundancy (mRMR) method stands out among the different feature selection techniques for dimensional reduction. The approach depends on mutual information (MI) between random variables as the basis for feature selection and is unaffected by modeling methods. However, it is necessary to clarify the benefits of the maximum correlation minimal redundancy algorithm in the context of near-infrared spectral feature selection, as well as its adaptability to various modeling methods. This research focuses on the NIR spectral dataset of maize germination rate, and the mRMR method is utilized to select spectral features. Based on the preceding foundation, we create models for Support Vector Regression, Gaussian Process Regression, Random Forest, and Neural Networks. The experimental findings demonstrate that, among the feature selection methods employed in this paper, the Max-Relevance Min-Redundancy algorithm outperforms others regarding the corn germination rate dataset.

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