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1.
Wiley Interdiscip Rev RNA ; 15(3): e1851, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38702938

RESUMO

Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.


Assuntos
Neoplasias , Oncogenes , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Oncogenes/genética , Regulação Neoplásica da Expressão Gênica
2.
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.

3.
J Agric Food Chem ; 72(15): 8840-8848, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38570314

RESUMO

A series of new 4-amino-3,5-dicholo-6-(5-aryl-substituted-1H-pyrazol-1-yl)-2-picolinic acid compounds were designed and prepared to discover herbicidal molecules. The inhibitory activities of all new compounds against the root growth ofArabidopsis thaliana were assayed. On the whole, the new synthesized compounds displayed good inhibition effects and had excellent herbicidal activities on root growth of weed at 500 µM. Importantly, a selection of compounds demonstrated comparable herbicidal properties to picloram. At the dosage of 250 g/ha, most of the compounds showed a 100% postemergence herbicidal activity to control Chenopodium album and Amaranthus retroflexus. Using compound V-2, the mechanism of action was investigated based on a phenotype study using AFB5-deficient Arabidopsis thaliana. It was found that the novel 6-pyrazolyl-2-picolinic acids were auxinic compounds. In addition, it was proposed that V-2 may be an immune activator due to its upregulation of defense genes and the increased content of jasmonic acid.


Assuntos
Arabidopsis , Herbicidas , Herbicidas/farmacologia , Relação Estrutura-Atividade , Ácidos Picolínicos/farmacologia , Arabidopsis/genética
4.
J Cancer Res Clin Oncol ; 150(5): 221, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687357

RESUMO

Vascular endothelial growth factor A (VEGF-A), a highly conserved dimeric glycoprotein, is a key regulatory gene and a marker molecule of angiogenesis. The upregulation of VEGF-A facilitates the process of tumor vascularization, thereby fostering the initiation and progression of malignant neoplasms. Many genes can adjust the angiogenesis of tumors by changing the expression of VEGF-A. In addition, VEGF-A also exhibits immune regulatory properties, which directly or indirectly suppresses the antitumor activity of immune cells. The emergence of VEGF-A-targeted therapy alone or in rational combinations has revolutionized the treatment of various cancers. This review discusses how diverse mechanisms in various tumors regulate VEGF-A expression to promote tumor angiogenesis and the role of VEGF-A in tumor immune microenvironment. The application of drugs targeting VEGF-A in tumor therapy is also summarized including antibody molecule drugs and traditional Chinese medicine.


Assuntos
Terapia de Alvo Molecular , Neoplasias , Neovascularização Patológica , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Inibidores da Angiogênese/uso terapêutico
5.
Food Chem ; 451: 139340, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38678649

RESUMO

Essential oils (EO), secondary metabolites of plants are fragrant oily liquids with antibacterial, antiviral, anti-inflammatory, anti-allergic, and antioxidant effects. They are widely applied in food, medicine, cosmetics, and other fields. However, the quality of EOs remain uncertain owing to their high volatility and susceptibility to oxidation, influenced by factors such as the harvesting season, extraction, and separation techniques. Additionally, the huge economic value of EOs has led to a market marked by widespread and varied adulteration, making the assessment of their quality challenging. Therefore, developing simple, quick, and effective identification techniques for EOs is essential. This review comprehensively summarizes the techniques for assessing EO quality and identifying adulteration. It covers sensory evaluation, physical and chemical property evaluation, and chemical composition analysis, which are widely used and of great significance for the quality evaluation and adulteration detection of EOs.

6.
Polymers (Basel) ; 16(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611189

RESUMO

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

8.
Thorac Cancer ; 15(13): 1072-1081, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38532546

RESUMO

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real-world study and a meta-analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. METHODS: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1-, 2-, and 3-year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1-year recurrence rate, R0 resection rate and adverse events. Moreover, a meta-analysis of 27 published literatures was also conducted for comparison. RESULTS: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1-, 2-, and 3-year OS rates were 91.41% (95% CI: 85.15%-95.63%), 75.00% (95% CI: 66.58%-82.23%) and 64.84% (95% CI: 55.91%-73.07%).ORR and DCR were 31.2% (95% CI: 23.31-39.99) and 64.1% (95% CI: 55.15%-72.38%), and the 1-year recurrence rate was 26.7% (95% CI: 22.5%-38.1%). Treatment-related events occurred in 96.1% but were acceptable. In a meta-analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1-year recurrence rate of 12%. CONCLUSION: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Terapia Neoadjuvante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Masculino , Feminino , Imunoterapia/métodos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto
9.
J Ethnopharmacol ; 328: 118007, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38492791

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.


Assuntos
Rosa , Ratos , Animais , Serotonina/metabolismo , Irã (Geográfico) , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/metabolismo , Transdução de Sinais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sinapses/metabolismo , Estresse Psicológico/tratamento farmacológico , Hipocampo , Modelos Animais de Doenças
10.
Molecules ; 29(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38338461

RESUMO

Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1-133), sesquiterpenoids (134-135), diterpenoids (136-142), sterols (143-147), phenols (148-167), flavonoids (168-186), phenylpropanoids (187-192) and others (193-206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154-156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value.


Assuntos
Compostos Fitoquímicos , Toona , Compostos Fitoquímicos/química , Medicina Tradicional , Antioxidantes/farmacologia , Hipoglicemiantes , Extratos Vegetais/química , Etnofarmacologia
11.
Eur J Clin Pharmacol ; 80(3): 465-474, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38216655

RESUMO

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.


Assuntos
Dexmedetomidina , Neoplasias da Bexiga Urinária , Adulto , Humanos , Masculino , Bexiga Urinária , Ressecção Transuretral de Bexiga , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Cateteres Urinários/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/complicações , Método Duplo-Cego
12.
Sci Rep ; 14(1): 2187, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273011

RESUMO

Bladder cancer is a common malignant tumor, and patients who have undergone radical cystectomy and urinary diversion require a lifelong abdominal stoma. This greatly affects their physiological, psychological, and social well-being. However, there is currently a lack of a self-assessment outcome scale specifically designed for bladder cancer patients with abdominal stomas. Therefore, we developed and validated a self-assessment outcome scale (PROS-BCAS) for Chinese bladder cancer patients with abdominal stomas. The scale was initially developed through literature research and expert consultation, and it comprised four dimensions: physiological, psychological, social, and treatment, with a total of 66 items. After item analysis, 44 items were retained. We collected scale data from 382 patients to examine its validity and reliability. The results showed that the PROS-BCAS scale had good content validity (S-CVI/Ave = 0.992), construct validity (KMO > 0.6), and discriminant validity (correlation coefficient 0.404-0.870). The Cronbach's alpha coefficients (0.801-0.954), test-retest reliability (0.778-0.956), and split-half reliability (0.896-0.977) all demonstrated good internal consistency for each dimension and the overall scale. The study demonstrated that the PROS-BCAS scale is a reliable and valid tool for accurately assessing the health-related quality of life of bladder cancer patients with abdominal stomas, providing reference for developing individualized clinical care plans.


Assuntos
Qualidade de Vida , Neoplasias da Bexiga Urinária , Humanos , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Psicometria/métodos , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , China
13.
Molecules ; 29(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38257244

RESUMO

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.


Assuntos
Arabidopsis , Herbicidas , Herbicidas/farmacologia , Ácidos Picolínicos/farmacologia , Picloram , Transporte Biológico , Ácidos Indolacéticos/farmacologia
14.
Toxicol Appl Pharmacol ; 483: 116800, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38219984

RESUMO

Nasopharyngeal carcinoma, a malignant tumor prevalent in southeast Asia and north Africa, still lacks effective treatment. Esketamine, an N-methyl-D-aspartatic acid (NMDA) receptor (NMDAR) antagonist, is widely used in clinical anesthesia. Emerging evidence suggests that esketamine plays an important role in inhibiting tumor cell activity. However, the underlying mechanisms of esketamine on nasopharyngeal carcinoma remain unknown. In this study, we found that esketamine inhibited the proliferation and migration of nasopharyngeal carcinoma cells. Mechanically, transcriptome sequencing and subsequent verification experiments revealed that esketamine promoted the apoptosis of nasopharyngeal carcinoma cells through endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway mediated by NMDAR. Additionally, when combined with esketamine, the inhibitory effect of cisplatin on the proliferation of nasopharyngeal carcinoma cells was significantly enhanced. These findings provide new insights into future anti-nasopharyngeal carcinoma clinical strategies via targeting the NMDAR/PERK/CHOP axis alone or in combination with cisplatin.


Assuntos
Ketamina , Neoplasias Nasofaríngeas , eIF-2 Quinase , Humanos , eIF-2 Quinase/metabolismo , Cisplatino/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Apoptose , Neoplasias Nasofaríngeas/tratamento farmacológico , Estresse do Retículo Endoplasmático , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Fator 4 Ativador da Transcrição/metabolismo
15.
Animal Model Exp Med ; 7(1): 56-70, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37740617

RESUMO

BACKGROUND: The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta-analysis. METHODS: Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2), were included. RESULTS: Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74-37.67), NT-proBNP (SMD: -0.41, 95% CI: -0.79-0.04), CI (MD: 0.47 L/min/m2, 95% CI: 0.17-0.77) and WHO-FC (OR: 0.564, 95% CI: 0.457-0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m2, 95% CI: 0.15-0.46) and WHO-FC (OR: 0.589, 95% CI: 0.376-0.922). Within 6 months of treatment, only the WHO-FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380-0.993; MD: 0.30 L/min/m2, 95% CI: 0.16-0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO-FC and NT-proBNP (MD: 40.87 m, 95% CI: 10.97-70.77; OR: 0.557, 95% CI: 0.440-0.705; SMD: -0.61, 95% CI: -1.17-0.05, respectively). CONCLUSIONS: Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low-dosage group. This finding is important for guiding individualized treatments.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Acetamidas , Pirazinas/efeitos adversos
16.
Chemistry ; 30(4): e202303169, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-37965803

RESUMO

In general, a large donor-acceptor dihedral angle is required to guarantee sufficient frontier molecular orbitals separation for thermally activated delayed fluorescence (TADF) emitters, which is intrinsically unfavorable for the radiative transition. We present a molecular design method favoring both reverse intersystem crossing (RISC) and radiative transitions even at a moderate D-A angle. A blue TADF emitter TrzBuCz-CN was designed with triazine/tert-butylcarbazole as donor/acceptor and cyano (CN) incorporated on the phenylene bridge. In comparison with the methyl decoration in similar way (TrzBuCz-Me), CN decoration reduced the D-A dihedral angle from 70° to 60°, which is intrinsically not favorable for sufficient FMO separation, but unexpectedly reduced the singlet and triplet energy gap (ΔEST ) and thus facilitated TADF feature by pulling down the lowest singlet state energy. While the reduced distorsion instead improved the HOMO-LUMO overlap and boosted the fluorescence quantum yield from 41 % to 94 %. The blue organic light-emitting diode of TrzBuCz-CN exhibited an external quantum efficiency of 13.7 % with emission peak at 466 nm, greatly superior to 6.0 % of TrzBuCz-Me. The result provides a feasible design strategy to facilitate both RISC and radiation processes by CN decoration of the linking bridge of TADF emitters.

17.
Cancer Gene Ther ; 31(3): 454-463, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38135697

RESUMO

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Tetraspaninas/genética , Tetraspaninas/metabolismo
18.
Hematology ; 28(1): 2277501, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37921501

RESUMO

BACKGROUND: Little is known about the changes and mechanisms of intestinal flora in primary immune thrombocytopenia (ITP) patients. AIM: To explore the structural and functional differences of intestinal flora between ITP patients and healthy controls, and clarify the correlation between intestinal flora and Th1/Th2 imbalance. METHODS: Feces from ITP patients and healthy controls were studied by 16S rRNA and metagenomic techniques at phylum, genus, species or functional levels. Blood samples were collected for the detection of interleukin -2 (IL-2) and IL-4 concentrations. RESULTS: The following changes in ITP patients were found: a decrease of Bacteroidetes phylum, an increase of Proteobacteria phylum and alterations of ten genera and 1045 species. IL-2 and IL-4 were significantly correlated with six and five genera, respectively. Species of C. freundii, C. rodentium, and C. youngae were negatively correlated with bleeding scores, and S. infantis was positively related to platelet counts. Functionally, the intestinal flora of ITP patients changed mainly in terms of motility, chemotaxis, membrane transport, and metabolism. CONCLUSION: The mechanism underlying functional and structural changes of intestinal flora in ITP patients may be related to inflammation and immunity, providing possibilities of probiotics or fecal transplants for ITP.


Assuntos
Microbioma Gastrointestinal , Púrpura Trombocitopênica Idiopática , Humanos , Interleucina-2 , Interleucina-4 , RNA Ribossômico 16S
19.
Chemosphere ; 344: 140378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806332

RESUMO

Hydrothermal carbonization of biogas slurry and animal manure into hydrochar could enhance waste recycling waste and minimize ammonia (NH3) volatilization from paddy fields. In this study, cattle manure-derived hydrochar prepared in the presence of Milli-Q water (CMWH) and biogas slurry (CMBSH), and biogas slurry-based hydrochar embedded with zeolite (ZHC) were applied to rice-paddy soil. The results demonstrated that CMBSH and ZHC treatments could significantly mitigate the cumulative NH3 volatilization and yield-scale NH3 volatilization by 27.9-45.2% and 28.5-45.4%, respectively, compared to the control group (without hydrochar addition), and significantly correlated with pH and ammonium-nitrogen (NH4+-N) concentration in floodwater. Nitrogen (N) loss via NH3 volatilization in the control group accounted for 24.9% of the applied N fertilizer, whereas CMBSH- and ZHC-amended treatments accounted for 13.6-17.9% of N in applied fertilizer. The reduced N loss improved soil N retention and availability for rice; consequently, grain N content significantly increased by 6.5-14.9% and N-use efficiency increased by 6.4-16.0% (P < 0.05), respectively. Based on linear fitting results, NH3 volatilization mitigation resulted from lower pH and NH4+-N concentration in floodwater that resulted from the acidic property and specific surface area of hydrochar treatments. Moreover, NH3-oxidizing archaea abundance in hydrochar-treated soil decreased by 40.9-46.9% in response to CMBSH and ZHC treatments, potentially suppressing NH4+-N transformation into nitrate and improving soil NH4+-N retention capacity. To date, this study applied biogas slurry-based hydrochar into paddy soil for the first time and demonstrated that ZHC significantly mitigated NH3 and increased N content. Overall, this study proposes an environmental-friendly strategy to recycle the wastes, biogas slurry, to the paddy fields to mitigate NH3 volatilization and increase grain yield of rice.


Assuntos
Amônia , Oryza , Bovinos , Animais , Amônia/química , Solo/química , Esterco/análise , Biocombustíveis/análise , Volatilização , Fertilizantes/análise , Carvão Vegetal/química , Nitrogênio/análise , Oryza/química , Grão Comestível/química
20.
Food Res Int ; 173(Pt 2): 113347, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803695

RESUMO

To mitigating the serious threat of harmful volatile substances to the health of infants, an alternative method of odor evaluation were proposed based on Headspace solid-phase microextraction (HS-SPME) combined with Gas Chromatography-Mass Spectrometry (GC-MS) to discriminate the degree of rancidity of infant formula rice flour (IFRF). Inspectors can simply calculate the rancidity degree of infant formula rice flour according to the regression equation based on the concentration of rancidity markers. The results showed that the joint application of OPLS-DA, molecular sensory experiments, and unsaturated fatty acids (UFAs) degradation experiments could successfully recognize the rancidity markers without collinearity in multiple linear regression analysis. The rancidity markers curve fitting was helpful for the establishment of multivariate regression model of rancidity grading. The model had an accuracy of more than 92.90% by the verification of odor evaluation. The application of the model to investigate the market IFRF samples showed that about 3% of the samples collected in the experiment were unsuitable for infant feeding. Therefore, the established model was considered to be a robust and less workload method to replace the olfactory evaluation method for discriminating the rancidity degree of IFRF.


Assuntos
Farinha , Microextração em Fase Sólida , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Fórmulas Infantis , Análise Multivariada
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