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1.
Clin Immunol ; 265: 110300, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950722

RESUMO

A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.

2.
Cardiovasc Diabetol ; 23(1): 234, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965584

RESUMO

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. MATERIALS AND METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression. RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: ß = 0.116; positive remodelling: ß = 0.138; spotty calcification: ß = 0.091; NOS: ß = 0.427; OS: ß = 0.659: SIS: ß = 1.114; SSS: ß = 2.987; PID: ß = 2.716, all P value < 0.001). CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.


Assuntos
Biomarcadores , LDL-Colesterol , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Valor Preditivo dos Testes , Calcificação Vascular , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Idoso , LDL-Colesterol/sangue , Biomarcadores/sangue , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/sangue , Fatores de Risco , Medição de Risco , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/diagnóstico , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Índice de Gravidade de Doença , Prognóstico , Estudos Transversais
3.
Environ Monit Assess ; 196(7): 664, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926195

RESUMO

Modification is widely used to enhance the adsorption performance of pristine hydrochar (HBC) and pyrochar (BC). However, comparisons between modified HBC and BC toward pollutant removal have rarely been reported. In this study, pristine HBC and BC derived from rice straw were first produced, and then citric acid (CA) was used as a modifier to synthesize CA-modified HBC (CAHBC) and CA-modified BC (CABC). Furthermore, the adsorption performance of biochars toward methylene blue (MB) was investigated. The results showed that BC exhibits relatively rough surfaces and contains more minerals (ash), whereas HBC has plentiful O-containing functional groups and fewer minerals. CA modification partially removed minerals from the surface of BC, which weakened the ion exchange, surface complexation, and n-π interaction, resulting in a lower adsorption ability toward MB. By contrast, CA produced more O-containing functional groups on the surface of HBC, which strengthened the hydrogen bonding and electrostatic interaction, thus increasing the adsorption capacity toward MB. The two-compartment model showed a good fit to the adsorption process of MB on CAHBC, and the isotherm data for MB adsorption by HBC and CAHBC are suitable for the Freundlich model. The highest adsorption amount of MB using CAHBC was 80.13 mg·g-1, which was 27.66% higher than that for CABC. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis indicated that the carboxyl groups in the surface functional groups of CAHBC played a crucial role in the MB adsorption process. In addition, CAHBC showed a good performance for a wide range of pH values (4.0-10.0) and under the interference of coexisting ions, and also presented a recycling ability. Furthermore, the adsorption of MB on CAHBC biochar was a spontaneous, exothermic, degree-of-randomness-increasing process. Consequently, CA modification of HBC is a promising strategy and could be used for MB removal from aquatic environments.


Assuntos
Carvão Vegetal , Ácido Cítrico , Azul de Metileno , Minerais , Poluentes Químicos da Água , Azul de Metileno/química , Adsorção , Ácido Cítrico/química , Carvão Vegetal/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Minerais/química , Oxigênio/química
4.
Medicine (Baltimore) ; 103(18): e38002, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701278

RESUMO

BACKGROUND: The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. RESULTS: We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. CONCLUSIONS: Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.


Assuntos
Antirreumáticos , Artrite Juvenil , Metanálise em Rede , Artrite Juvenil/tratamento farmacológico , Humanos , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adalimumab/uso terapêutico , Adalimumab/efeitos adversos , Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Teorema de Bayes
5.
J Environ Manage ; 360: 121140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754190

RESUMO

Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.


Assuntos
Biocombustíveis , Carvão Vegetal , Ciprofloxacina , Pirólise , Ciprofloxacina/química , Carvão Vegetal/química , Biocombustíveis/análise , Adsorção , Poluentes Químicos da Água/química , Temperatura , Porosidade , Cinética
6.
Biochem Biophys Res Commun ; 722: 150170, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38797152

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent progressive liver disease. Currently, there is only one drug for NAFLD treatment, and the options are limited. Phosphodiesterase-4 (PDE-4) inhibitors have potential in treating NAFLD. Therefore, this study aims to investigate the effect of roflumilast on NAFLD. Here, we fed ob/ob mice to induce the NAFLD model by GAN diet. Roflumilast (1 mg/kg) was administered orally once daily. Semaglutide (20 nmol/kg), used as a positive control, was injected subcutaneously once daily. Our findings showed that roflumilast has beneficial effects on NAFLD. Roflumilast prevented body weight gain and improved lipid metabolism in ob/ob-GAN NAFLD mice. In addition, roflumilast decreased hepatic steatosis by down-regulating the expression of hepatic fatty acid synthesis genes (SREBP1c, FASN, and CD36) and improving oxidative stress. Roflumilast not only reduced liver injury by decreasing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also ameliorated hepatic inflammation by reducing the gene expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6). Roflumilast lessened liver fibrosis by inhibiting the expression of fibrosis mRNA (TGFß1, α-SMA, COL1a1, and TIMP-1). Collectively, roflumilast could ameliorate NAFLD, especially in reducing hepatic steatosis and fibrosis. Our findings suggested a PDE-4 inhibitor roflumilast could be a potential drug for NAFLD.


Assuntos
Aminopiridinas , Benzamidas , Ciclopropanos , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Inibidores da Fosfodiesterase 4 , Animais , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Masculino , Camundongos , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Obesos , Estresse Oxidativo/efeitos dos fármacos , Dieta
7.
Int J Neurosci ; : 1-8, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38654424

RESUMO

OBJECTIVE: To evaluate the effects of argatroban on the levels of Hcy, hs-CRP and FIB in patients with acute cerebral infarction (ACI). METHODS: A retrospective analysis was performed on 382 patients with ACI who were hospitalized in the Department of Neurology of our hospital from January 2017 to December 2019. Among them, 158 patients received conventional treatment as the control group and 224 patients received combined treatment with argatroban as the study group. NHISS score, mRS score, Hcy, hs-CRP, FIB level, quality of life, adverse reactions were compared between the two groups after treatment. The levels of Hcy and hs-CRP in patients with different mRS scores were compared. RESULTS: A superior clinical efficacy of the study group was observed than the control group (p < 0.05). The study group witnessed a remarkably lower NHISS score, Hcy, hs-CRP and FIB level as compare to the control group (p < 0.05). The ADL and FMA scores in the study group were higher than those in the control group (p < 0.05). The levels of Hcy and hs-CRP in mRS 0-2 patients were lower than those in mRS 3-6 patients (p < 0.05). CONCLUSION: Argatroban in ACI patients can significantly enhance the clinical efficacy and improve the quality of life. It is closely related to the reduction of Hcy and hs-CRP levels, but the mechanism needs to be further studied.

8.
Psychiatry Res ; 336: 115894, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38598946

RESUMO

Social determinants of health (SDoH) have been linked to a higher likelihood of experiencing mental health problems. This study aimed to investigate whether the accumulation of unfavorable SDoH is associated with depression symptom. Data was gathered from a representative population participating in the U.S. National Health and Nutrition Examination Survey spanning from 2005 to 2018. Self-reported SDoH were operationalized according to the criteria outlined in Healthy People 2030, with a cumulative measure of unfavorable SDoH calculated for analysis. The presence of depression symptom was identified using the Patient Health Questionnaire in a representative sample of 30,762 participants (49.2 % males) representing 1,392 million non-institutionalized U.S. adults, with 2,675 (8.7 %) participants showing depression symptom. Unfavorable SDoH were found to be significantly and independently associated with depression symptom. Individuals facing multiple unfavorable SDoHs were more likely to experience depression symptom (P for trend < 0.001). For instance, a positive association was observed in participants exposed to six or more unfavorable SDoHs with depression symptom (AOR = 3.537, 95 % CI: 1.781, 7.075, P-value < 0.001). The findings emphasize that the likelihood of developing depression symptom significantly increases when multiple SDoHs are present, compared to just a single SDoH.


Assuntos
Depressão , Inquéritos Nutricionais , Determinantes Sociais da Saúde , Humanos , Masculino , Feminino , Adulto , Estados Unidos/epidemiologia , Depressão/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Determinantes Sociais da Saúde/estatística & dados numéricos , Adulto Jovem , Idoso , Fatores Socioeconômicos , Adolescente
9.
Clin Immunol ; 263: 110199, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565329

RESUMO

Cell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 ligand-receptor complex was significantly upregulatedin aged skin, showing the predominant paracrine effect of keratinocytes on fibroblasts. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARγ protein, which thus significantly increased the degree of fibroblast senescence, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study reveals that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, ultimately accelerating fibroblast senescence.


Assuntos
Antígenos de Diferenciação de Linfócitos B , Fibroblastos , Antígenos de Histocompatibilidade Classe II , Fatores Inibidores da Migração de Macrófagos , Análise de Célula Única , Envelhecimento da Pele , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismo , Humanos , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Fibroblastos/metabolismo , Envelhecimento da Pele/genética , Envelhecimento da Pele/fisiologia , Análise de Célula Única/métodos , Transdução de Sinais , Senescência Celular/genética , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Análise de Sequência de RNA , Queratinócitos/metabolismo , Queratinócitos/imunologia , PPAR gama/metabolismo , PPAR gama/genética , Pessoa de Meia-Idade , Masculino , Feminino , Pele/metabolismo , Pele/imunologia , Células Cultivadas , Adulto
10.
Nutr Metab Cardiovasc Dis ; 34(6): 1496-1507, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38658226

RESUMO

BACKGROUND AND AIMS: Engaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. METHODS AND RESULTS: A total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8-18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. CONCLUSION: Our study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.


Assuntos
Causas de Morte , Jardinagem , Inquéritos Nutricionais , Fatores de Proteção , Comportamento de Redução do Risco , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Fatores de Tempo , Medição de Risco , Idoso , Estilo de Vida Saudável
11.
Org Biomol Chem ; 22(17): 3453-3458, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38596838

RESUMO

A brand-new procedure for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones has been disclosed via a HOTf or Fe(OTf)3-catalyzed dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes. Aryl, alkenyl and alkyl terminal alkynes are suitable to couple with a broad range of 3-hydroxyisoindolinones to afford the desired products in moderate to good yields. This protocol features the use of an inexpensive catalyst, mild reaction conditions, broad substrate scope and easy elaboration of the products.

12.
Chemistry ; 30(33): e202400995, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38600034

RESUMO

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

13.
J Am Chem Soc ; 146(13): 9335-9346, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38501695

RESUMO

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before. The reaction features excellent selectivity and impressive reactivity. It proceeds under mild conditions, avoiding the use of superstoichiometric amounts of additives and metal catalysts to simplify the synthetic procedure. The accessibility and scalability of the reaction allowed for the rapid construction of a ligand library for optimization of asymmetric Heck-type cyclization, laying the foundation for a broad range of applications of chiral BPMOs in catalysis.

14.
Cancer Lett ; 589: 216810, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494151

RESUMO

Pancreatic cancer is characterized by desmoplasia; crosstalk between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) leads to the deposition of extracellular matrix proteins in the tumor environment resulting in poor vascularity. Targeting either PCCs or PSCs individually has produced mixed results, and there is currently no effective strategy to target both cell types simultaneously. Previously, we demonstrated, through in vitro cell culture experiments, that a specific gold nanoparticle-based nanoformulation containing the anti-EGFR antibody cetuximab (C225) as a targeting agent and gemcitabine as a chemotherapeutic agent effectively targets both PCCs and PSCs simultaneously. Herein, we extend our studies to test the ability of these in vitro tested nano formulations to inhibit tumor growth in an orthotopic co-implantation model of pancreatic cancer in vivo. Orthotopic tumors were established by co-implantation of equal numbers of PCCs and PSCs in the mouse pancreas. Among the various formulations tested, 5 nm gold nanoparticles coated with gemcitabine, cetuximab and poly-ethylene glycol (PEG) of molecular weight 1000 Da, which we named ACGP441000, demonstrated optimal efficacy in inhibiting tumor growth. The current study reveals an opportunity to target PCCs and PSCs simultaneously, by exploiting their overexpression of EGFR as a target, in order to inhibit pancreatic cancer growth.


Assuntos
Nanopartículas Metálicas , Neoplasias Pancreáticas , Animais , Camundongos , Gencitabina , Ouro , Cetuximab/farmacologia , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Distribuição Tecidual , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Sistemas de Liberação de Medicamentos/métodos , Células Estreladas do Pâncreas/metabolismo
15.
Food Chem ; 447: 138926, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38471278

RESUMO

4-Terpineol (4-TA), a typical monocyclic monoterpene essential oil compound with important biological activities, poor stability and solubility severely hamper its biological activities. To date, ß-cyclodextrin (ß-CD) encapsulating essential oil to form inclusion complexes (ICs) is considered as a satisfactory treatment. Nevertheless, the detailed inclusion mechanism of ß-CD for 4-TA especially the behavior of 4-TA during inclusion formation have not available yet. Herein, 4-TA/ß-CD ICs were successfully synthesized by the co-precipitation method, and hydrogen bonds and hydrophobic interactions played a key role in the formation of ICs, and the isopropyl of 4-TA entered the cavity through the wide rim of ß-CD. Moreover, the release profile demonstrated that high RH (85 % and 99 %) triggered the release of TA from ICs. This study suggests the great potential of cyclodextrin inclusion strategy for improving the stability and sustained release of 4-TA in food preservation application.


Assuntos
Ciclodextrinas , Óleos Voláteis , beta-Ciclodextrinas , Umidade , beta-Ciclodextrinas/química , Ciclodextrinas/química , Óleos Voláteis/química , Solubilidade
16.
BMC Pediatr ; 24(1): 90, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302958

RESUMO

BACKGROUND: Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). CASE PRESENTATION: Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. CONCLUSION: Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. SUITABLE FOR PEOPLE WITH: Infectious Diseases; Neonatology; Obstetrics.


Assuntos
Exantema , Doenças do Recém-Nascido , Icterícia , Tifo por Ácaros , Feminino , Humanos , Recém-Nascido , China , Dispneia , Febre/diagnóstico , Tifo por Ácaros/diagnóstico
17.
J Clin Periodontol ; 51(5): 558-570, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38200631

RESUMO

AIM: To examine the impact of both individual and cumulative social determinants of health (SDoH) on the likelihood of developing periodontitis, while also exploring any gender disparities in this relationship. MATERIALS AND METHODS: Data of self-reported SDoH domains and sub-items based on Healthy People 2030 were obtained from the U.S. National Health and Nutrition Examination Surveys between 1999 and 2014. Logistic regression models, weighted by survey responses, were used to examine the relationship between SDoH (including eight sub-items and the cumulative number of unfavourable SDoH) and periodontitis. The results were further analysed by gender. RESULTS: A total of 18,075 participants (8867 males and 9208 females) were included in the main analysis, of which 5814 (32.2%) had periodontitis. The study found that certain unfavourable SDoH were individually associated with higher odds of periodontitis, and the cumulative number of unfavourable SDoH was positively linked to the odds of developing periodontitis. Furthermore, males exposed to more unfavourable SDoH appeared to be more susceptible to developing periodontitis than females. CONCLUSIONS: The findings suggest that unfavourable SDoH, especially when they accumulate, are associated with an increased odds of periodontitis and contribute to gender disparities within the U.S.


Assuntos
Periodontite , Determinantes Sociais da Saúde , Feminino , Masculino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Modelos Logísticos , Periodontite/epidemiologia
18.
Inorg Chem ; 63(3): 1613-1624, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38195398

RESUMO

Trinitarian designs in the morphology, components, and microstructure remain challenging for advanced electromagnetic wave absorption (EMWA) materials with light weight, strong absorption, and well-defined structure-function relationships. Herein, a series of X-doped MoS2/Cu9S5 with multilevel honeycomb structures (X-MoS2/Cu9S5 MHs, X = P, Si, Ge) were designed by space-confined growth and in situ sulfidation of a polyoxometalate-based metal-organic framework. X-MoS2/Cu9S5 MHs possess low density, high surface area, and abundant cation-cuprum and anion-sulfur double vacancies (VCu and VS) simultaneously that are unmatched by conventional EMWA materials. Also, the systematic investigation of the doping effect of various polyoxometalate heteroatoms on VCu and VS in the microhoneycomb has been conducted. Experimental results and density functional theory calculations reveal that the excellent EMWA performance (-56.21 dB) results from the synergistic effect of morphology design, component optimization, and vacancy regulation. This study not only provides an important opportunity to understand a morphology-component-microstructure strategy in electromagnetic wave absorption but also builds a noteworthy bridge between bioinspired engineering and microscale absorbers.

19.
PeerJ ; 12: e16548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188156

RESUMO

Reduced fertilizer efficiency caused by excessive use of nitrogen (N) fertilizer is a major problem in agriculture and a hot topic of research. Most studies have focused on the effect of N application rate on N efficiency, whereas there are limited studies on changing the N form to improve N yield and efficiency. Here, the effects of different N application rates and nitrate-to-ammonium N ratios on post-anthesis carbon (C) and N metabolism and maize yield under shallow-buried drip irrigation were investigated. Two rates of N application (210 kg·ha-1 (NA1) and 300 kg·ha-1 (NA2)) and three nitrate-to-ammonium N ratios (2:1 (NF1), 3:1 (NF2), and 4:1 (NF3)) were utilized. Post-anthesis photosynthetic characteristics, activities of key enzymes in photosynthetic C and N metabolism, nonstructural carbohydrate content, post-anthesis N accumulation and transportation, yield, and N-use efficiency were determined. At both N application rates, NF2 treatment enhanced photosynthetic activity in the ear-leaf at silking stage and promoted key enzyme activities of C and N metabolic pathways, compared with NF1 and NF3. Furthermore, NF2 significantly increased nonstructural carbohydrate accumulation (4.00-64.71%), post-anthesis N accumulation and transportation (11.00-38.00%), and grain yield (2.60-13.08%). No significant differences between NA1 and NA2 were observed under NF2 in most of the measured variables; however, NA1 had higher N-use efficiency. Thus, the optimal treatment under shallow-buried drip irrigation was a N application rate of 210 kg ha-1 and a nitrate-to-ammonium N ratio of 3:1. These findings provide theoretical guidance on appropriate N applications for high-yield maize production.


Assuntos
Compostos de Amônio , Zea mays , Nitratos , Fertilizantes , Fotossíntese , Carbono , Nitrogênio , Carboidratos
20.
J Ethnopharmacol ; 321: 117409, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37972909

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhizae Radix et Rhizoma, a Chinese herb known as licorice, is frequently incorporated in traditional Chinese medicine (TCM) formulations, due to its significant medicinal value and sweet taste. Despite licorice's merits, no systematic scientometric study has yet been conducted to analyze licorice research trends over the past 25 years. AIM OF THE STUDY: We conducted this study with the aim to provide researchers with a comprehensive overview of research advances in the application of licorice as a TCM ingredient and to offer valuable insights to guide future endeavors in this research field. METHODS: We selected licorice-related research papers published between 1997 and 2021 from the Web of Science Core Collection then conducted a scientometric analysis using VOSviewer and CiteSpace software tools. RESULTS: A total of 4883 licorice-related publications, including 4511 research papers, 372 review papers, and their cited references, were included in the analysis. Most of these articles were authored by researchers in China (36.8%), including major contributors Wang Ying, Ye Min, and Zhang Yu. The Journal of Ethnopharmacology (impact factor = 5.4) hosted the greatest number of papers (145 articles). Keyword cluster analysis revealed three keyword categories indicating that current licorice research is focused on licorice quality control and identification of licorice active ingredients and associated pharmacological mechanisms. CONCLUSION: This study provides a comprehensive overview of licorice-related research trends over the past 25 years as based on quantitative and qualitative analyses of published licorice-related articles. The results of this multi-level analysis of licorice research related to TCM formulations, chemical compositions, and pharmacological effects should provide valuable reference data and insights to guide future research endeavors in this field.


Assuntos
Medicamentos de Ervas Chinesas , Glycyrrhiza , Medicamentos de Ervas Chinesas/química , Glycyrrhiza/química , Etnofarmacologia , China
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