Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Front Endocrinol (Lausanne) ; 15: 1373869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628582

RESUMO

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.


Assuntos
Acromegalia , Adenoma , Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acromegalia/complicações , Adenoma/diagnóstico , Síndrome de Cushing/diagnóstico , Hipersecreção Hipofisária de ACTH/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações
2.
BMC Plant Biol ; 24(1): 188, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486139

RESUMO

BACKGROUND: Proper flowering time is important for the growth and development of plants, and both too early and too late flowering impose strong negative influences on plant adaptation and seed yield. Thus, it is vitally important to study the mechanism underlying flowering time control in plants. In a previous study by the authors, genome-wide association analysis was used to screen the candidate gene SISTER OF FCA (SSF) that regulates FLOWERING LOCUS C (FLC), a central gene encoding a flowering suppressor in Arabidopsis thaliana. RESULTS: SSF physically interacts with Protein arginine methyltransferase 5 (PRMT5, SKB1). Subcellular co-localization analysis showed that SSF and SKB1 interact in the nucleus. Genetically, SSF and SKB1 exist in the same regulatory pathway that controls FLC expression. Furthermore, RNA-sequencing analysis showed that both SSF and SKB1 regulate certain common pathways. CONCLUSIONS: This study shows that PRMT5 interacts with SSF, thus controlling FLC expression and facilitating flowering time control.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo
3.
Langmuir ; 39(49): 17600-17610, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38039395

RESUMO

Cation-π interaction is one of the most important noncovalent interactions identified in biosystems, which has been proven to play an essential role in the strong adhesion of marine mussels. In addition to the well-known catecholic amino acid, l-3,4-dihydroxyphenylalanine, mussel foot proteins are rich in various aromatic moieties (e.g., tyrosine, phenylalanine, and tryptophan) and cationic residues (e.g., lysine, arginine, and histidine), which favor a series of short-range cation-π interactions with adjustable strengths, serving as a prototype for the development of high-performance underwater adhesives. This work highlights our recent advances in understanding and utilizing cation-π interactions in underwater adhesives, focusing on three aspects: (1) the investigation of the cation-π interaction mechanisms in mussel foot proteins via force-measuring techniques; (2) the modulation of cation-π interactions in mussel mimetic polymers with the variation of cations, anions, and aromatic groups; (3) the design of wet adhesives based on these revealed principles, leading to functional materials in the form of films, coacervates, and hydrogels with biomedical and engineering applications. This review provides valuable insights into the development and optimization of smart materials based on cation-π interactions.


Assuntos
Materiais Biomiméticos , Bivalves , Animais , Materiais Biomiméticos/química , Proteínas/química , Adesivos/química , Di-Hidroxifenilalanina/química , Cátions/química , Bivalves/química
4.
Acta Neuropathol Commun ; 11(1): 188, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012690

RESUMO

Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Humanos , Neoplasias Encefálicas/patologia , Neoplasias Embrionárias de Células Germinativas/genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Epigênese Genética
5.
Front Neurosci ; 17: 1191596, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901430

RESUMO

Metastatic PitNETs are a rare life-threatening condition with poor prognosis and documentation. Due to the scarce literature and lack of precise treatment, we hope to better characterise PitNET using the next-generation whole exon sequencing (WES) and RNA sequencing. This case study outlines a 54 years-old man and a 52 years-old woman who were both diagnosed with PitNET and analysis of peripheral blood and tumours were performed by WES and RNA sequencing. Analysis showed that DICER1 mutations in precancerous lesions and LAG3 overexpression were significant in aiding the prognosis and diagnosis of PitNETs. The first case with overexpressed LAG3 and DICER1 mutation died 26 months later, and the second case with LAG3 overexpression achieved partial remission. This study revealed that heightened expression of LAG3 offered promising targets for ICI and mutations in DICER1 could provide markers for effective diagnosis and prognosis.

6.
Int J Biol Macromol ; 251: 126539, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37634787

RESUMO

Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized ß-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can "re-educate" macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the "don't eat me" CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.

7.
J Colloid Interface Sci ; 650(Pt B): 1525-1535, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37487283

RESUMO

HYPOTHESIS: Conventional coating strategies and materials for bio-applications with protective, diagnostic, and therapeutic functions are commonly limited by their arduous preparation processes and lack of on-demand functionalities. Herein, inspired by the 'root-leaf' structure of grass, a series of novel polyacrylate-conjugated proteins can be engineered with sticky bovine serum albumin (BSA) protein as a 'root' anchoring layer and a multifunctional polyacrylate as a 'leaf' functional layer for the facile coating procedure and versatile surface functionalities. EXPERIMENTS: The engineered proteins were synthesized based on click chemistry, where the 'root' layer can universally anchor onto both organic and inorganic substrates through a facile dip/spraying method with excellent stability in harsh solution conditions, thanks to its multiple adaptive molecular interactions with substrates that further elucidated by molecular force measurements between the 'root' BSA protein and substrates. The 'leaf' conjugated-polyacrylates imparted coatings with versatile on-demand functionalities, such as resistance to over 99% biofouling in complex biofluids, pH-responsive performance, and robust adhesion with various nanomaterials. FINDINGS: By synergistically leveraging the universal anchoring capabilities of BSA with the versatile physicochemical properties of polyacrylates, this study introduces a promising and facile strategy for imparting novel functionalities to a myriad of surfaces through engineering natural proteins and biomaterials for biotechnical and nanotechnical applications.


Assuntos
Incrustação Biológica , Materiais Revestidos Biocompatíveis , Materiais Revestidos Biocompatíveis/química , Soroalbumina Bovina/química , Propriedades de Superfície
8.
Front Neurosci ; 17: 1169179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476834

RESUMO

Introduction: Intracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs. Methods: Meta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs. Results: Nine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results. Discussion: This study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis.

9.
ACS Appl Mater Interfaces ; 15(15): 19560-19573, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37036950

RESUMO

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.


Assuntos
Quitosana , Microgéis , Temperatura , Adesivos , Hidrogéis/farmacologia , Hidrogéis/química , Quitosana/química , Polímeros/química , Cicatrização , Soroalbumina Bovina , Sulfametoxazol , Concentração de Íons de Hidrogênio
10.
J Cancer Res Clin Oncol ; 149(10): 8051-8076, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37002510

RESUMO

BACKGROUND: Abnormal metabolism is the main hallmark of cancer, and cancer metabolism plays an important role in tumorigenesis, metastasis, and drug resistance. Therefore, studying the changes of tumor metabolic pathways is beneficial to find targets for the treatment of cancer diseases. The success of metabolism-targeted chemotherapy suggests that cancer metabolism research will provide potential new targets for the treatment of malignant tumors. PURPOSE: The aim of this study was to systemically review recent research findings on targeted inhibitors of tumor metabolism. In addition, we summarized new insights into tumor metabolic reprogramming and discussed how to guide the exploration of new strategies for cancer-targeted therapy. CONCLUSION: Cancer cells have shown various altered metabolic pathways, providing sufficient fuel for their survival. The combination of these pathways is considered to be a more useful method for screening multilateral pathways. Better understanding of the clinical research progress of small molecule inhibitors of potential targets of tumor metabolism will help to explore more effective cancer treatment strategies.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Metabolismo Energético
11.
Front Pharmacol ; 13: 977582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467046

RESUMO

Background and objectives: The US FDA and Health Canada have successively published potential red flags for acute pancreatitis caused by sodium-dependent glucose transporter 2 inhibitors (SGLT-2i). However, existing studies have focused on case reports. We aimed to assess the possible association of SGLT-2i with acute pancreatitis by analyzing postmarketing adverse events reported in the FDA adverse event reporting system (FAERS), to explore risk factors for SGLT-2i-related acute pancreatitis death, and to build a nomogram. Methods and Results: We used a disproportionality analysis of suspected acute pancreatitis-related reports in the FAERS database of patients from the use of SGLT-2i from the first quarter of 2013 to the fourth quarter of 2021. Single-factor and multi-factor logistic regression analyses were performed using the relevant clinical information of patients, and risk factors were combined with the age of patients to construct a SGLT-2i risk prediction model for acute pancreatitis-related death. A total of 757 reports were retrieved. The largest number of acute pancreatitis-related cases were caused by canagliflozin (317 reports), which was also the strongest agent associated with acute pancreatitis, with the information component (IC 2.41, lower 95% one-sided confidence interval 2.16), the reporting odds ratio (ROR 5.37, 95% two-sided confidence interval 4.8-5.99), and the empirical Bayesian geometric mean (EBGM 5.32, lower 90% one-sided confidence interval 4.85). The median time to acute pancreatitis was 54 (interquartile range [IQR] 14-131) days, and approximately 83% of adverse events occurred within 6 months. Odds ratio(OR) adjusted by acute pancreatitis and the coadministration of SGLT-2i with dipeptidyl peptidase 4 inhibitor (DPP-4i), glucagon-like peptide 1 analog (GLP-1RA), and angiotensin converting enzyme inhibitor (ACEIs) was 1.39, 1.97, and 1.34, respectively, all of which were statistically significant. Logistic regression analysis showed that different SGLT-2i type and their combinations with statins were independent risk factors for acute pancreatitis mortality in the patients (p < 0.05). The mortality risk prediction model showed good discrimination and clinical applicability in both the training set (AUC 0.708) and the validation set (AUC 0.732). Conclusion: SGLT-2i may increase the risk of acute pancreatitis especially within the first 6 months of drug administration. Combination with DPP-4i, GLP-1RA or ACEIs significantly increases the risk of acute pancreatitis. In addition, different SGLT-2i type and their combination with statins are risk factors that can predict the risk of death following acute pancreatitis.

12.
Biomed Pharmacother ; 155: 113707, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36122520

RESUMO

Due to the complexity and particularity of cancer cell microenvironments, redox responsive drug delivery systems (DDSs) for cancer therapy have been extensively explored. Compared with widely reported cancer treatment systems based on disulfide bonds, diselenide bonds have better redox properties and greater anticancer efficiency. In this review, the significance and application of diselenide bonds in DDSs are summarized, and the stimulation sensitivity of diselenide bonds is comprehensively reported. The potential and prospects for the application of diselenide bonds in next-generation anticancer drug treatment systems are extensively discussed.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/uso terapêutico , Oxirredução , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Dissulfetos , Portadores de Fármacos/química , Microambiente Tumoral
13.
J Stroke Cerebrovasc Dis ; 31(9): 106692, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35932542

RESUMO

OBJECTIVES: The use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration. MATERIALS AND METHODS: This study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. RESULTS: Overall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%. CONCLUSIONS: Early PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.


Assuntos
Edema Encefálico , Biomarcadores , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/terapia , Edema , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/terapia , Humanos , Prognóstico , Tomografia Computadorizada por Raios X
14.
Artigo em Inglês | MEDLINE | ID: mdl-35805805

RESUMO

Although it has been widely recognized that land fragmentation has increased chemical fertilizer application, little is known about the role of technology adoption in mitigating these adverse effects. To empirically examine the relationship between land fragmentation, technology adoption and chemical fertilizer application, we developed a mediation model. We applied our analysis to a survey data set encompassing 1388 farm-level samples collected in 14 Chinese provinces in 2019. Our study demonstrated that land fragmentation can not only directly increase chemical fertilizer application but also indirectly increase it by hindering the adoption of agricultural mechanization technologies (AMT's) and soil testing fertilization technologies (STFT's). Both are recognized as potent drivers of fertilizer use reductions. Moreover, the adoption of information and communications technologies (ICT's) can help mitigate the negative effects of land fragmentation on technology adoption, thus reducing chemical fertilizer application intensity (CFAI). However, the direct effects of land fragmentation on CAFI was unaffected by ICT's. Our findings suggest that ICT's have revolutionized farmer recognition, promotion and adoption of agricultural technologies by increasing awareness and diffusion of agricultural technology information.


Assuntos
Agricultura , Fertilizantes , China , Fertilizantes/análise , Solo , Tecnologia
15.
J Colloid Interface Sci ; 627: 180-193, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35842968

RESUMO

In this contribution, carbon quantum dots (CQDs) modified 3D-flower like BiOX (X = Cl, Br, I) photocatalyst were successfully prepared via a facile mechanical compounding method. The crystal structure, surface composition, morphologies, optical properties and photocatalytic activities were investigated in detail. The photocatalytic activity of the as-obtained photocatalyst were evaluated by degradation of rhodamine B (RhB) and Levofloxacin (LEV) under near IR-UV-vis light irradiation, the CQDs/BiOX composite displayed enhanced photocatalytic activity as compared with individual BiOX materials. The CQDs/BiOX composite had the outstanding light harvesting and electron transfer ability because of the ordered ultrathin nanosheet structure of the BiOX, the formation of metal Bi under photoinduction, and the synergistic effects between CQDs and pure BiOX. Antibacterial activity and effects on Rye seeds growth of the LEV degradation intermediate were also researched. Reactive-species-trapping experiments exhibited that h+ and O2- were the active reactive species during photodegradation process. This work provided an effective and simple strategy for designing QDs modified Bi-rich oxyhalides in organic pollutant containing wastewater treatment.


Assuntos
Poluentes Ambientais , Pontos Quânticos , Antibacterianos/química , Antibacterianos/farmacologia , Bismuto , Carbono , Catálise , Levofloxacino , Fotólise , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Rodaminas
16.
Biomed Pharmacother ; 149: 112894, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367763

RESUMO

In recent years, with improvements in treatments for heart failure (HF), the survival period of patients has been extended. However, the emergence of some patients with repeated hospitalizations due to their worsening conditions and low survival rates followed. Currently, few drugs are available for such patients. Vericiguat was first drug approved for the treatment of symptomatic patients with chronic HF with reduced ejection fraction (HFrEF) to reduce the occurrence of worsening HF. This article provides comprehensive information about vericiguat in terms of drug design and development, structure-activity relationship (SAR), synthesis, pharmacological efficacy, and clinical practice. In addition, insights into the current vericiguat trials and treatments of HF are also discussed.


Assuntos
Insuficiência Cardíaca , Compostos Heterocíclicos com 2 Anéis , Insuficiência Cardíaca/tratamento farmacológico , Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Humanos , Pirimidinas , Guanilil Ciclase Solúvel , Volume Sistólico , Vasodilatadores/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-36612550

RESUMO

Turnover has been a serious concern to social service organizations. A lack of committed social workers is a risk to organizational performance and service quality. Therefore, it is vital to better understand the leaving process of social work practitioners. The study constructed a moderated mediation model to examine the mediating role of job satisfaction between employees' professionalism and turnover intention and the moderating role of the perceived level of managerialism in the context of social work organizations. A total of 667 participants from Guangzhou, Shenzhen, and Shanghai in China were recruited to complete the survey. Results presented that job satisfaction plays a full mediation role in the relationship between professionalism and turnover intention. In addition, the positive relationship between professionalism and job satisfaction, as well as the negative relationship between professionalism and turnover intention were moderated by managerialism. The findings enrich knowledge about turnover among social workers in the context of China and inspire to foster professionalism among service workers to improve job satisfaction and alleviate turnover intention and actual turnover as well as to apply management techniques and structures properly to strengthen the effect of professionalism on promoting job satisfaction and on preventing turnover intention.


Assuntos
Satisfação no Emprego , Assistentes Sociais , Humanos , Profissionalismo , China , Reorganização de Recursos Humanos , Intenção , Inquéritos e Questionários
18.
J Colloid Interface Sci ; 607(Pt 2): 1993-2009, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34798708

RESUMO

HYPOTHESIS: Lung surfactant protects lung tissue and reduces the surface tension in the alveoli during respiration. Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5), which invades primely through inhalation, can deposit on and interact with the surfactant layer, leading to changes in the biophysical and morphological properties of the lung surfactant. EXPERIMENTS: Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and clinical surfactant Calsurf were investigated with a PM2.5 model injected into the water subphase, which were characterized by surface pressure-area isotherms, Brewster angle microscopy, atomic force microscopy, fluorescent microscopy, and x-ray photoelectron spectroscopy. The binding between DPPC/Calsurf and PM2.5 was studied using isothermal titration calorimetry. FINDINGS: PM2.5 induced the expansion of the monolayers at low surface pressure (п) and film condensation at high п. Aggregation of PM2.5 mainly occurred at the interface of liquid expanded/liquid condensed (LE/LC) phases. PM2.5 led to slimmer and ramified LC domains on DPPC and the reduction of nano-sized condensed domains on Calsurf. Both DPPC and Calsurf showed fast binding with PM2.5 through complex binding modes attributed to the heterogeneity and amphiphilic property of PM2.5. This study improves the fundamental understanding of PM2.5-lung surfactant interaction and shows useful implications of the toxicity of PM2.5 through respiration process.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Surfactantes Pulmonares , Produtos Biológicos , Material Particulado , Fosfolipídeos , Propriedades de Superfície , Tensoativos
19.
ACS Appl Mater Interfaces ; 13(40): 48239-48251, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34601867

RESUMO

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.


Assuntos
Adesivos/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Poloxâmero/farmacologia , Taninos/farmacologia , Adesividade , Adesivos/química , Animais , Antibacterianos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Poloxâmero/química , Pele/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Suínos , Taninos/química , Água/química
20.
ACS Nano ; 15(6): 9913-9923, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34037373

RESUMO

Developing effective internal wound dressing materials is important for postoperative tissue regeneration while remains a challenge due to the poor biological environment-adaptability of conventional materials. Here, we report an example of injectable self-healing hydrogel based on gastric environment-adaptive supramolecular assembly, and have explored its application for gastric perforation healing. By leveraging the gastric environment-modulated supramolecular interactions, the self-assembled hydrogel network is orchestrated with sensitive thermo-responsibility, injectability, printability and rapid self-healing capability. The hydrogel dressing can effectively inhibit the attachment of microorganisms and demonstrates outstanding antibiofouling property. In vivo rat model further demonstrates the as-prepared hydrogel dressing simplifies the surgical procedures, reduces postoperative complications as well as enhances the healing process of gastric perforation compared with the conventional treatment. This work provides useful insights into the development of biological environment-adaptive functional materials for various biomedical applications.


Assuntos
Hidrogéis , Cicatrização , Animais , Bandagens , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA