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1.
J Dig Dis ; 25(3): 148-155, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38624062

RESUMO

Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.


Assuntos
Antibacterianos , Furazolidona , Infecções por Helicobacter , Helicobacter pylori , Furazolidona/uso terapêutico , Furazolidona/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Humanos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Quimioterapia Combinada , Farmacorresistência Bacteriana , Resultado do Tratamento
2.
Behav Sci (Basel) ; 14(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38540516

RESUMO

It is reported that teachers' satisfaction levels are lower and stress levels are higher than other professional groups in many countries. This is especially true for science, technology, engineering, and mathematics (STEM) teachers. Considering job satisfaction has a direct impact on turnover intention, low satisfaction levels have led to high turnover rates and thus exacerbated the shortages of STEM teachers. Hence, there is an urgent need to explore the antecedents of novice STEM teachers' job satisfaction. This study proposes a new model to show how novice STEM teachers' personality traits and perceived social support influence their job satisfaction. A total of 2592 novice STEM teachers in eighteen randomly selected high schools in China were recruited. Data were analyzed using the structural equation modeling approach. The results illustrated that most novice STEM teachers had low levels of job satisfaction. Novice STEM teachers' personality traits could directly and indirectly impact their job satisfaction. Meanwhile, novice STEM teachers' job satisfaction was also directly influenced by work engagement and indirectly influenced by their perceived social support. Our findings theoretically contribute to the understanding of the determinants of STEM teachers' job satisfaction and have important practical implications.

3.
Front Med (Lausanne) ; 11: 1367900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500953

RESUMO

Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.

4.
PLoS One ; 19(2): e0278434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38349894

RESUMO

INTRODUCTION: Many regions in the world are using the population health approach and require a means to measure the health of their population of interest. Population health frameworks provide a theoretical grounding for conceptualization of population health and therefore a logical basis for selection of indicators. The aim of this scoping review was to provide an overview and summary of the characteristics of existing population health frameworks that have been used to conceptualize the measurement of population health. METHODS: We used the Population, Concept and Context (PCC) framework to define eligibility criteria of frameworks. We were interested in frameworks applicable for general populations, that contained components of measurement of health with or without its antecedents and applied at the population level or used a population health approach. Eligible reports of eligible frameworks should include at least domains and subdomains, purpose, or indicators. We searched 5 databases (Pubmed, EMBASE, Web of Science, NYAM Grey Literature Report, and OpenGrey), governmental and organizational sites on Google and websites of selected organizations using keywords from the PCC framework. Characteristics of the frameworks were summarized descriptively and narratively. RESULTS: Fifty-seven frameworks were included. The majority originated from the US (46%), Europe (23%) and Canada (19%). Apart from 1 framework developed for rural populations and 2 for indigenous populations, the rest were for general urban populations. The numbers of domains, subdomains and indicators were highly variable. Health status and social determinants of health were the most common domains across all frameworks. Different frameworks had different priorities and therefore focus on different domains. CONCLUSION: Key domains common across frameworks other than health status were social determinants of health, health behaviours and healthcare system performance. The results in this review serve as a useful resource for governments and healthcare organizations for informing their population health measurement efforts.


Assuntos
Atenção à Saúde , Humanos , Canadá , Europa (Continente)
5.
Small ; : e2311336, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385851

RESUMO

The electrocatalytic conversion of nitrate (NO3 - ) to NH3 (NO3 RR) at ambient conditions offers a promising alternative to the Haber-Bosch process. The pivotal factors in optimizing the proficient conversion of NO3 - into NH3 include enhancing the adsorption capabilities of the intermediates on the catalyst surface and expediting the hydrogenation steps. Herein, the Cu/Cu2 O/Pi NWs catalyst is designed based on the directed-evolution strategy to achieve an efficient reduction of NO3 ‾. Benefiting from the synergistic effect of the OV -enriched Cu2 O phase developed during the directed-evolution process and the pristine Cu phase, the catalyst exhibits improved adsorption performance for diverse NO3 RR intermediates. Additionally, the phosphate group anchored on the catalyst's surface during the directed-evolution process facilitates water electrolysis, thereby generating Hads on the catalyst surface and promoting the hydrogenation step of NO3 RR. As a result, the Cu/Cu2 O/Pi NWs catalyst shows an excellent FE for NH3 (96.6%) and super-high NH3 yield rate of 1.2 mol h-1  gcat. -1 in 1 m KOH and 0.1 m KNO3 solution at -0.5 V versus RHE. Moreover, the catalyst's stability is enhanced by the stabilizing influence of the phosphate group on the Cu2 O phase. This work highlights the promise of a directed-evolution approach in designing catalysts for NO3 RR.

6.
Heliyon ; 10(4): e26233, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404766

RESUMO

Satisfaction with learning management systems (LMSs) is an essential indicator of students' e-learning experiences and reflects the quality of e-learning. Applying the technology satisfaction model, the present study aimed to investigate medical and nursing students' satisfaction with LMSs and its predictors. We conducted our survey at a medical university located in East China and received a total of 329 effective responses. Structural equation modelling was used to analyse the data. Our findings confirmed that perceived ease of use and perceived usefulness were two direct predictors of medical and nursing students' satisfaction with LMSs. Furthermore, the influence of perceived usefulness on satisfaction was more powerful than that of perceived ease of use. This study also substantiated that computer self-efficacy and perceived ease of use can indirectly impact medical and nursing students' satisfaction with LMSs. Our research effectively links the theoretical hypotheses with empirical findings, highlighting the central role of Computer Self-Efficacy (CSE), perceived ease of use, and perceived usefulness in shaping medical and nursing students' satisfaction with LMSs. Our findings contributed to the understanding of the technology satisfaction model and medical and nursing students' e-learning during the COVID-19 pandemic.

7.
Entropy (Basel) ; 26(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38392368

RESUMO

This paper investigates achieving leader-following consensus in a class of multi-agent systems with nonlinear dynamics. Initially, it introduces a dynamic event-triggered strategy designed to effectively alleviate the strain on the system's communication resources. Subsequently, a distributed control strategy is proposed and implemented in the nonlinear leader-follower system using the dynamic event-triggered mechanism, aiming to ensure synchronization across all nodes at an exponential convergence speed. Thirdly, the research shows that under the dynamic event-triggered strategy the minimum event interval of any two consecutive triggers guarantees the elimination of Zeno behavior. Lastly, the validity of the calculation results is verified by a simulation example.

8.
J Dermatol ; 51(3): 391-402, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214545

RESUMO

Generalized pustular psoriasis (GPP) is a potentially life-threatening skin disease. Although several medications are approved for treating GPP in Japan, there are limited data on real-world treatment patterns or drug survival (the number of prescribed days of treatment). This retrospective cohort study describes drug survival and treatment patterns of patients with newly diagnosed GPP (International Classification of Diseases, 10th Revision code L40.1), and ≥1 year of follow-up, using de-identified claims data (Medical Data Vision Co., Ltd.) from January 2016 to August 2021. Most (97.0%) of the 434 Japanese patients received first-line therapy of etretinate (26.4%), topical medications (14.7%), or cyclosporin (14.3%); 80.0% and 60.1% of patients received a second and third line of therapy (LOT), respectively. Use of etretinate (12.6%) and cyclosporin (5.9%) decreased in second-line therapies, whereas use of biologics (interleukin [IL]-17, 14.3%; IL-23 inhibitors, 7.6%) and topical medications (22.1%) increased or remained consistent. Approximately 50% of biologics were prescribed in combination with systemic medications or systemic corticosteroids. Median (range) time to next therapy (TTNT) was 2.8 (0.03-48.07) months for first-line therapy and 3.3 (0.03-52.97) months for all other LOTs. TTNT was longer for combination therapies (up to 16.5 months) compared with monotherapies (up to 7.5 months). Biologics exhibited longer drug survival with fewer treatment episodes compared with non-biologic systemic medications. Among frequently used therapies, the median (95% confidence interval) drug survival was 8.8 (5.8-11.8) months for etretinate, 4.3 (2.2-6.9) months for systemic corticosteroids, and 19.6 (16.1-26.7) months for secukinumab. Treatment patterns varied considerably, highlighting the need for treatment algorithms and effective, well-tolerated medications to support patients to help them remain on long-term therapy.


Assuntos
Produtos Biológicos , Ciclosporinas , Etretinato , Psoríase , Humanos , Etretinato/uso terapêutico , Japão , Estudos Retrospectivos , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Corticosteroides/uso terapêutico , Ciclosporinas/uso terapêutico
9.
Clin Res Hepatol Gastroenterol ; 47(10): 102233, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879535

RESUMO

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Antibacterianos/uso terapêutico , Estudos Transversais , Inibidores da Bomba de Prótons/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Bismuto/uso terapêutico , Amoxicilina/uso terapêutico , Resultado do Tratamento
10.
Biotechnol Biofuels Bioprod ; 16(1): 126, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550714

RESUMO

BACKGROUND: Xylo-oligomers are a kind of high value-added products in biomass fractionation. Although there are several chemical methods to obtain xylo-oligomers from biomass, the reports about the deep eutectic solvents (DESs)-mediated co-production of xylo-oligomers and fermentable sugars and the related kinetic mechanism are limited. RESULTS: In this work, glycolic acid-based DESs were used to obtain xylo-oligomers from corncob. The highest xylo-oligomers yield of 65.9% was achieved at 120 °C for 20 min, of which the functional xylo-oligosaccharides (XOSs, DP 2-5) accounted for up to 31.8%. Meanwhile, the enzymatic digestion of cellulose and xylan in residues reached 81.0% and 95.5%, respectively. Moreover, the addition of metal inorganic salts significantly accelerated the hydrolysis of xylan and even the degradation of xylo-oligomers in DES, thus resulting in higher selectivity of xylan removal. AlCl3 showed the strongest synergistic effect with DES on accelerating the processes, while FeCl2 is best one for xylo-oligomers accumulation, affording the highest xylo-oligomers yield of 66.1% for only 10 min. Furthermore, the kinetic study indicates that the 'potential hydrolysis degree' model could well describe the xylan hydrolysis processes and glycolic acid/lactic acid (3:1) is a promising solvent for xylo-oligomers production, in particular, it worked well with FeCl2 for the excellent accumulation of xylo-oligomers. CONCLUSIONS: Glycolic acid-based deep eutectic solvents can be successfully applied in corncob fractionation with excellent xylo-oligomers and fermentable sugars yields on mild conditions, and the large amount of xylo-oligosaccharides accumulation could be achieved by specific process controlling. The strategies established here can be useful for developing high-valued products from biomass.

11.
Nat Med ; 29(6): 1424-1436, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37280275

RESUMO

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.


Assuntos
Cisplatino , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Cisplatino/uso terapêutico , Gencitabina , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/uso terapêutico , Microambiente Tumoral
12.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1833-1839, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282958

RESUMO

The odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees was analyzed and the relationship between the odor variation and the mildewing degree was explored. A fast discriminant model was established according to the response intensity of electronic nose. The α-FOX3000 electronic nose was applied to analyze the odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees and the radar map was used to analyze the main contributors among the volatile organic compounds. The feature data were processed and analyzed by partial least squares discriminant analysis(PLS-DA), K-nearest neighbor(KNN), sequential minimal optimization(SMO), random forest(RF) and naive Bayes(NB), respectively. According to the radar map of the electronic nose, the response values of three sensors, namely T70/2, T30/1, and P10/2, increased with the mildewing, indicating that the Pollygonati Rhizoma produced alkanes and aromatic compounds after the mildewing. According to PLS-DA model, Pollygonati Rhizoma samples of three mildewing degrees could be well distinguished in three areas. Afterwards, the variable importance analysis of the sensors was carried out and then five sensors that contributed a lot to the classification were screened out: T70/2, T30/1, PA/2, P10/1 and P40/1. The classification accuracy of all the four models(KNN, SMO, RF, and NB) was above 90%, and KNN was most accurate(accuracy: 97.2%). Different volatile organic compounds were produced after the mildewing of Pollygonati Rhizoma, and they could be detected by electronic nose, which laid a foundation for the establishment of a rapid discrimination model for mildewed Pollygonati Rhizoma. This paper shed lights on further research on change pattern and quick detection of volatile organic compounds in moldy Chinese herbal medicines.


Assuntos
Medicamentos de Ervas Chinesas , Compostos Orgânicos Voláteis , Nariz Eletrônico , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Teorema de Bayes , Medicamentos de Ervas Chinesas/análise , Análise Discriminante
13.
Chemistry ; 29(33): e202300552, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-36995358

RESUMO

Inspired by alkene addition to the Ru and Re tris(thiolate) complexes via carbon-sulfur bond formation/cleavage reactions along with a periodic extension catalysis notion, a comparative study of the electronic structures, mechanisms, and reactivities for ethylene addition to the Os and Tc tris(thiolate) complexes was performed by DFT and high-level ab initio quantum calculations. The oxidized Os and Tc complexes were revealed to exhibit sufficient radical characters on the ligands to support their reaction with ethylene, whereas neutral Tc tris(thiolate) complex featuring little thiyl radical character renders no reactivity toward ethylene. Differential reactivities of these tris(thiolate) complexes was deemed to derive from the synergy of the thiyl radical character, the electronegativity, the row, and the charge. Extending from Ru and Re tris(thiolate) complexes to their Os and Tc counterparts can help us to get insightful rationales that would promote further research on alkene addition to metal-stabilized thiyl radicals.


Assuntos
Alcenos , Metais , Ligantes , Etilenos
14.
Helicobacter ; 28(2): e12953, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738099

RESUMO

BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Quimioterapia Combinada , Amoxicilina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Tamanho Corporal , Peso Corporal , Resultado do Tratamento , Claritromicina/uso terapêutico
15.
Inorg Chem ; 62(6): 2548-2560, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36719396

RESUMO

In retrospect to the complexity induced by the noninnocent ligands in identifying the transition metal's oxidation state and correlating the ligand's noninnocence with reactivity, the reactions of alkene/alkyne addition to rhenium/ruthenium tris(thiolate) complexes are particularly good cases for shedding light on the chemistry of the dppbt ligand, including its noninnocent nature, ligand-centered mechanism, and origin of differential reactivity. Density functional theory (DFT) combined with the high-level ab initio calculations performed herein demonstrates that, upon alkene/alkyne addition, the orbital symmetry properly regulates the reaction to form ligand-centered cis-interligand dithioethers as the most favorable pathway. The neutral and cationic Re and Ru dithioethers are revealed via DFT calculations to be in a low-spin ground state; on the contrary, high-level ab initio methods confirm that the dicationic Re-dithioethers exhibit obvious multireference character with antiferromagnetic coupling between Re-dyz and S1-py. The metal-stabilized thiyl radicals play a pivotal role in delivering the reactivity of [RuL3]+ and [ReL3]+/2+ toward alkene/alkyne rather than [ReL3], where [RuL3]+ and [ReL3]+/2+ present significant radical characters on ligand S2, yet neutral [ReL3] has little such feature, from which differential reactivity arises. Faster styrene addition to Ru tris(thiolate) in contrast to Re tris(thiolate) has been properly interpreted using DFT calculations with major products assigned. The deeper understanding gained in this work would illuminate further experimental exploration in adding alkene/alkyne to other metal-stabilized thiyl radicals.

16.
Anal Bioanal Chem ; 415(9): 1641-1655, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36719439

RESUMO

Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLC‒MS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1ß were reduced, and the phosphorylation of IKKß and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.


Assuntos
Técnicas Biossensoriais , Hepatopatia Gordurosa não Alcoólica , Humanos , Cromatografia Líquida , Fatores Imunológicos , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo , Lotus/química , Folhas de Planta/química
18.
Molecules ; 27(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36014515

RESUMO

Monkeypox is an emerging epidemic of concern. The disease is caused by the monkeypox virus and an increasing global incidence with a 2022 outbreak that has spread to Europe amid the COVID-19 pandemic. The new outbreak is associated with novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involves the use of tecovirimat. However, there is otherwise limited pharmacopoeia and research interest in monkeypox. In this study, virtual screening and molecular dynamics were employed to explore the potential repurposing of multiple drugs previously approved by the FDA or other jurisdictions for other applications. Several drugs are predicted to tightly bind to viral proteins, which are crucial in viral replication, including molecules which show high potential for binding the monkeypox D13L capsid protein, whose inhibition has previously been demonstrated to suppress viral replication.


Assuntos
COVID-19 , Mpox , Humanos , Mpox/tratamento farmacológico , Monkeypox virus/genética , Pandemias , Preparações Farmacêuticas , Estados Unidos
19.
Cell Biochem Biophys ; 80(3): 547-554, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35776316

RESUMO

Oxidized low-density lipoprotein (ox-LDL) is a type of modified cholesterol that promotes apoptosis and inflammation and advances the progression of heart failure. Leucine-zipper and sterile-α motif kinase (ZAK) is a kinase of the MAP3K family which is highly expressed in the heart and encodes two variants, ZAKα and ZAKß. Our previous study serendipitously found opposite effects of ZAKα and ZAKß in which ZAKß antagonizes ZAKα-induced apoptosis and hypertrophy of the heart. This study aims to test the hypothesis of whether ZAKα and ZAKß are involved in the damaging effects of ox-LDL in the cardiomyoblast. Cardiomyoblast cells H9c2 were treated with different concentrations of ox-LDL. Cell viability and apoptosis were measured by MTT and TUNEL assay, respectively. Western blot was used to detect apoptosis, hypertrophy, and pro-survival signaling proteins. Plasmid transfection, pharmacological inhibition with D2825, and siRNA transfection were utilized to upregulate or downregulate ZAKß, respectively. Ox-LDL concentration-dependently reduces the viability and expression of several pro-survival proteins, such as phospho-PI3K, phospho-Akt, and Bcl-xL. Furthermore, ox-LDL increases cleaved caspase-3, cleaved caspase-9 as indicators of apoptosis and increases B-type natriuretic peptide (BNP) as an indicator of hypertrophy. Overexpression of ZAKß by plasmid transfection attenuates apoptosis and prevents upregulation of BNP. Importantly, these effects were abolished by inhibiting ZAKß either by D2825 or siZAKß application. Our results suggest that ZAKß upregulation in response to ox-LDL treatment confers protective effects on cardiomyoblast.


Assuntos
Lipoproteínas LDL , Peptídeo Natriurético Encefálico , Animais , Apoptose , Hipertrofia , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Peptídeo Natriurético Encefálico/genética , Proteínas Quinases , Ratos , Regulação para Cima
20.
Curr Med Sci ; 42(4): 856-862, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35819656

RESUMO

OBJECTIVE: The role of urgent endoscopy in nonvariceal upper gastrointestinal hemorrhage (NVUGIH) remains controversial. We designed a retrospective study to compare the outcomes between urgent endoscopy (within 12 h) and non-urgent endoscopy for patients with NVUGIH. METHODS: A total of 540 hospitalized patients with NVUGIH were included in our study. Patients who received endoscopy within 12 h or after 12 h were divided into two groups, the urgent and non-urgent endoscopy groups, respectively. The clinical outcomes including rebleeding, mortality, endoscopic re-intervention, need for emergency surgery and interventional radiotherapy were compared between the groups. Patients with Glasgow-Blatchford scores (GBS) <12 and ≥12 were defined as the lower- and high-risk groups, respectively, and the predictors of rebleeding and mortality in both groups were analyzed individually. RESULTS: Patients with NVUGIH in the urgent endoscopy group had a higher rate of rebleeding (27.6% vs. 16.9%, P=0.003) and blood transfusion (73.2% vs. 55.5%, P<0.001) than those in the non-urgent endoscopy group, while the mortality and the length of hospitalization were not significantly different between the groups (P>0.05). For lower-risk patients, urgent endoscopy was independently associated with a higher likelihood of rebleeding (adjusted OR: 1.73, 95% CI: 1.03-2.88), while it was not associated with in-hospital mortality. However, the urgent need for endoscopy was not associated with rebleeding and inhospital mortality in high-risk patients. CONCLUSION: Endoscopy within 12 h did not provide any advantage in the outcomes of patients with NVUGIH, and may even lead to an increased rebleeding rate in lower-risk patients.


Assuntos
Endoscopia Gastrointestinal , Hemorragia Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/cirurgia , Mortalidade Hospitalar , Hospitalização , Humanos , Estudos Retrospectivos
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