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1.
Adv Healthc Mater ; : e2400235, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569198

RESUMO

Cancer immunotherapy by immune checkpoint inhibitors (ICIs) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, it is shown that the development of an antibody-conjugated nanogel (ANGel), consisting of N-isopropylacrylamide-co-acrylic acid and antibody-binding protein (protein A), potentiates the efficacy of two ICI monoclonal antibodies (mAbs) (cytotoxic-T-lymphocyte-associated antigen 4 and programmed death ligand-1 mAbs). Compared with mAb treatment alone, treatment with a bispecific ANGel surface-conjugated with the mAbs significantly decreases both the survival of Michigan Cancer Foundation-7 (MCF-7) and M D Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cells in vitro and the burden of 4T1-luciferase-2-derived orthotopic syngeneic tumors in vivo. The bispecific ANGel is also more potent than the conventional treatment at prolonging survival in animals with triple-negative breast cancer. The advantage of the bispecific ANGel over other engineered bispecific antibodies arises not only from the adaptability to link multiple antibodies quickly and easily, but also from the capability to maintain the anticancer effect steadily at subcutaneously delivered tumor site. This finding has an important implication for cancer immunotherapy, opening a new paradigm to treat solid tumors.

2.
Plant Physiol Biochem ; 208: 108522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38493663

RESUMO

In staple crops, such as rice (Oryza sativa L.), pollen plays a crucial role in seed production. However, the molecular mechanisms underlying rice pollen germination and tube growth remain underexplored. Notably, we recently uncovered the redundant expression and mutual interaction of two rice genes encoding cyclic nucleotide-gated channels (CNGCs), OsCNGC4 and OsCNGC5, in mature pollen. Building on these findings, the current study focused on clarifying the functional roles of these two genes in pollen germination and tube growth. To overcome functional redundancy, we produced gene-edited rice plants with mutations in both genes using the CRISPR-Cas9 system. The resulting homozygous OsCNGC4 and OsCNGC5 gene-edited mutants (oscngc4/5) exhibited significantly lower pollen germination rates than the wild type (WT), along with severely reduced fertility. Transcriptome analysis of the double oscngc4/5 mutant revealed downregulation of genes related to receptor kinases, transporters, and cell wall metabolism. To identify the direct regulators of OsCNGC4, which form a heterodimer with OsCNGC5, we screened a yeast two-hybrid library containing rice cDNAs from mature anthers. Subsequently, we identified two calmodulin isoforms (CaM1-1 and CaM1-2), NETWORKED 2 A (NET2A), and proline-rich extension-like receptor kinase 13 (PERK13) proteins as interactors of OsCNGC4, suggesting its roles in regulating Ca2+ channel activity and F-actin organization. Overall, our results suggest that OsCNGC4 and OsCNGC5 may play critical roles in pollen germination and elongation by regulating the Ca2+ gradient in growing pollen tubes.


Assuntos
Oryza , Oryza/fisiologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Germinação/genética , Pólen/metabolismo , Tubo Polínico/genética , Calmodulina/genética , Calmodulina/metabolismo , Fosfotransferases , Nucleotídeos Cíclicos/metabolismo
3.
Eur J Med Res ; 29(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167158

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a significant contributor to morbidity and mortality worldwide, with CVD and post-acute COVID-19 associated CVD increasing. It remains unknown whether COVID-19 patients with weight gain are at a high risk for CVD events. Therefore, the primary objective of this study is to investigate the association between weight control and the risk of CVD following COVID-19. METHODS: The study included 2,024,728 adults who participated in two rounds of health screening between 2017 and 2020. The final cohort, which included 70,996 participants in the COVID-19 group and 212,869 participants in the control group. The adjusted hazard ratio of BMI change to CVD risk was calculated using Cox proportional hazards regression. RESULTS: We identified a total of 2869 cases of CVD (861 events for COVID-19 group and 2,008 events for the control group). Compared to individuals with a stable BMI, COVID-19 patients without obesity had an increased risk of CVD (adjusted hazard ratio [aHR] = 2.28; 95% confidence interval [CI], 1.15-4.53; p-value = 0.018). Additionally, non-COVID-19 patients with obesity also exhibited a higher risk of CVD (aHR = 1.58; 95% CI, 1.01-2.47; p-value = 0.046). CONCLUSION: In conclusion, people who gained weight during the pandemic, regardless of their weight category, had a significantly higher risk of CVD associated with COVID-19 compared to those who maintained their weight before the pandemic.


Assuntos
COVID-19 , Doenças Cardiovasculares , Adulto , Humanos , Fatores de Risco , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Índice de Massa Corporal , COVID-19/complicações , COVID-19/epidemiologia , Aumento de Peso , Obesidade/complicações , Obesidade/epidemiologia
4.
J Korean Med Sci ; 38(49): e415, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38111284

RESUMO

BACKGROUND: While accumulating evidence indicates chronic kidney disease as a risk factor for coronavirus disease 2019 (COVID-19), the association between normal or mildly decreased kidney function and COVID-19 is unaddressed. Here, we have examined the association of an increase in estimated glomerular filtration rate (eGFR) with the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes among patients within normal to mildly decreased kidney function. METHODS: The patients who participated in both health screenings from period I (2017-2018) to II (2019-2020) were enrolled to our study. All participants were categorized into four groups according to the changes in eGFR stage from period I to II: 1) persistently stage G1, 2) from stage G2 to G1, 3) from stage G1 to G2, 4) persistently stage G2. In addition, the changes in eGFR value were defined by subtracting its value of period I from II. Patients were followed up for SARS-CoV-2 infection from January 1, 2021 to any diagnosis of COVID-19 or December 31, 2021, whichever happened first. In addition, those with SARS-CoV-2 infection were followed-up for one month after diagnosis to analyze severe COVID-19. Adjusted odds ratio (aOR) was calculated using multivariable-adjusted logistic regression. RESULTS: We identified 159,427 patients with and 1,804,798 patients without SARS-CoV-2 infection. The risk of SARS-CoV-2 infection decreased when eGFR stage changed from G2 to G1 (aOR, 0.957; 95% confidence interval [CI], 0.938-0.977) and persistently maintained at G1 (aOR, 0.966; 95% CI, 0.943-0.990), compared with the persistently stage G2 group. In addition, the risk showed an inverse relationship with changes in eGFR value, which was depicted by restricted cubic spline curves. For the overall risk of severe COVID-19, the persistently stage G1 showed the lowest risk (aOR, 0.897; 95% CI, 0.827-0.972), followed by those from stage G1 to G2 (aOR, 0.900; 95% CI, 0.828-0.978) and those from stage G2 to G1 (aOR, 0.931; 95% CI, 0.871-0.995), compared with the persistently stage G2 group. CONCLUSION: An increase in eGFR was negatively associated with the risk of SARS-CoV-2 infection and severe COVID-19 among normal or mildly decreased kidney function. For severe COVID-19, maintaining higher baseline eGFR may act as a protective factor against its risk.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Humanos , COVID-19/complicações , SARS-CoV-2 , Estudos de Casos e Controles , Fatores de Risco , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/complicações
5.
Rice (N Y) ; 16(1): 51, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37971600

RESUMO

Root hairs are extensions of epidermal cells on the root tips that increase the root contract surface area with the soil. For polar tip growth, newly synthesized proteins and other materials must be incorporated into the tips of root hairs. Here, we report the characterization of PRX102, a root hair preferential endoplasmic reticulum peroxidase. During root hair growth, PRX102 has a polar localization pattern within the tip regions of root hairs but it loses this polarity after growth termination. Moreover, PRX102 participates in root hair outgrowth by regulating dense cytoplasmic streaming toward the tip. This role is distinct from those of other peroxidases playing roles in the root hairs and regulating reactive oxygen species homeostasis. RNA-seq analysis using prx102 root hairs revealed that 87 genes including glutathione S-transferase were downregulated. Our results therefore suggest a new function of peroxidase as a player in the delivery of substances to the tips of growing root hairs.

6.
Plants (Basel) ; 12(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37631170

RESUMO

The collar region plays a crucial role in leaf angle formation and plant architecture, which is important for improving crop yield given the challenges of diminishing arable land and changing environmental conditions. To determine collar region-preferential genes (CRPGs) affecting plant architecture and crop yield, we conducted genome-wide transcriptomic analysis. By integrating our RNA sequencing data with public rice anatomical expression data, we identified 657 CRPGs. Verification involved testing six randomly selected CRPGs, all of which exhibited collar-preferential expression. The functional significance of CRPGs was assessed via Gene Ontology enrichment analysis, utilizing MapMan and KEGG, and literature analysis provided additional information for characterized CRPGs. Our findings revealed links between manipulating leaf angle and phytohormone-related pathways and stress responses. Moreover, based on the CRPGs, five transcription factors downstream of the liguleless 1 (LG1) gene were identified. Overall, the identified CRPGs provide potential targets for further research and breeding applications aimed at improving crop productivity by manipulating leaf architecture.

7.
ACS Appl Polym Mater ; 5(3): 2195-2202, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-37552750

RESUMO

The efficacy of coronavirus disease 2019 (COVID-19) vaccination is closely related to the serum levels of SARS-CoV-2-neutralizing antibodies (NAb) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Therefore, the rapid and quantitative measurement of SARS-CoV-2 NAb in the sera of vaccinated individuals is essential to develop an effective vaccine and further achieve population immunity, that is, herd immunity. The plaque reduction neutralization test, the gold standard for NAb effectiveness in serological tests, is accurate but requires biosafety level 3 facilities because of the use of the virus, which hampers its application in common laboratories and clinical practice. Here, we developed a bioresponsive nanogel-based surface plasmon resonance (nSPR) platform that detects SARS-CoV-2 NAb in clinical samples without complicated pretreatment. We found that multivalent protein binding (MPB) between the nanogel-conjugated RBD protein and SARS-CoV-2 NAb yields significantly enhanced SPR signals compared to the nonspecific interference from serum proteins in the nSPR assay. The excellence of our nanogel-based SARS-CoV-2 NAb test is due to its selectivity for NAb, with resistance to all other proteins, allowing the rapid detection and quantification of NAbs in each individual. Importantly, this nSPR assay provides a NAb detection platform for easier and safer COVID-19 vaccination strategies.

8.
J Lipid Atheroscler ; 12(2): 189-200, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265848

RESUMO

Objective: Hypercholesterolaemia transforms macrophages into lipid-laden foam cells in circulation, which can activate the immune response. Compromised autophagy and inflammatory cytokines are involved in the pathogenesis and progression of metabolic diseases. The aim of this study was to identify the role of autophagy as a modulator of the inflammatory response and cytotoxicity in macrophages under hypercholesterolaemic conditions. Methods: High cholesterol-induced cytokine secretion and alteration of autophagy-associated molecules were confirmed by cytokine array and western blot analysis, respectively. To confirm whether autophagic regulation affects high cholesterol-induced cytokine release and cytotoxicity, protein levels of autophagic molecules, cell viability, and cytotoxicity were measured in cultured macrophages treated autophagy enhancers. Results: Cholesterol treatment increased cytokine secretion, cellular toxicity, and lactate dehydrogenase release in lipopolysaccharide (LPS)-primed macrophages. Concomitantly, altered levels of autophagy-related molecules were detected in LPS-primed macrophages under hypercholesterolaemic conditions. Treatment with autophagy enhancers reversed the secretion of cytokines, abnormally expressed autophagy-associated molecules, and cytotoxicity of LPS-primed macrophages. Conclusion: Autophagy enhancers inhibit inflammatory cytokine secretion and reduce cytotoxicity under metabolic disturbances, such as hypercholesterolaemia. Modulation of autophagy may be a novel approach to control the inflammatory response observed in metabolic diseases.

10.
J Integr Plant Biol ; 65(9): 2218-2236, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37195059

RESUMO

Pollen tube growth is essential for successful double fertilization, which is critical for grain yield in crop plants. Rapid alkalinization factors (RALFs) function as ligands for signal transduction during fertilization. However, functional studies on RALF in monocot plants are lacking. Herein, we functionally characterized two pollen-specific RALFs in rice (Oryza sativa) using multiple clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9-induced loss-of-function mutants, peptide treatment, expression analyses, and tag reporter lines. Among the 41 RALF members in rice, OsRALF17 was specifically expressed at the highest level in pollen and pollen tubes. Exogenously applied OsRALF17 or OsRALF19 peptide inhibited pollen tube germination and elongation at high concentrations but enhanced tube elongation at low concentrations, indicating growth regulation. Double mutants of OsRALF17 and OsRALF19 (ralf17/19) exhibited almost full male sterility with defects in pollen hydration, germination, and tube elongation, which was partially recovered by exogenous treatment with OsRALF17 peptide. This study revealed that two partially functionally redundant OsRALF17 and OsRALF19 bind to Oryza sativa male-gene transfer defective 2 (OsMTD2) and transmit reactive oxygen species signals for pollen tube germination and integrity maintenance in rice. Transcriptomic analysis confirmed their common downstream genes, in osmtd2 and ralf17/19. This study provides new insights into the role of RALF, expanding our knowledge of the biological role of RALF in regulating rice fertilization.


Assuntos
Oryza , Tubo Polínico , Tubo Polínico/genética , Pólen/genética , Transdução de Sinais , Peptídeos
11.
Small ; 19(27): e2300564, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37010002

RESUMO

Having a permanent omniphobicity on the inner surface of the tube can bring enormous advantages, such as reducing resistance and avoiding precipitation during mass transfer. For example, such a tube can prevent blood clotting when delivering blood composed of complex hydrophilic and lipophilic compounds. However, it is very challenging to fabricate micro and nanostructures inside a tube. To overcome these, a wearability and deformation-free structural omniphobic surface is fabricated. The omniphobic surface can repel liquids by its "air-spring" under the structure, regardless of surface tension. Furthermore, it is not lost an omniphobicity under physical deformation like curved or twisted. By using these properties, omniphobic structures on the inner wall of the tube by the "roll-up" method are fabricated. Fabricated omniphobic tubes still repels liquids, even complex liquids like blood. According to the ex vivo blood tests for medical usage, the tube can reduce thrombus formation by 99%, like the heparin-coated tube. So, the surface will soon replace typical coating-based medical surfaces or anticoagulation blood vessels.


Assuntos
Nanoestruturas , Trombose , Humanos , Coagulação Sanguínea , Interações Hidrofóbicas e Hidrofílicas , Anticoagulantes/farmacologia
12.
Plants (Basel) ; 11(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36432876

RESUMO

In the angiosperm, pollen germinates and rapidly expands the pollen tube toward the ovule. This process is important for plant double fertilization and seed setting. It is well known that the tip-focused calcium gradient is essential for pollen germination and pollen tube growth. However, little is known about the Ca2+ channels that play a role in rice pollen germination and tube growth. Here, we divided the 16 cyclic nucleotide-gated channel (CNGC) genes from rice into five subgroups and found two subgroups (clades II and III) have pollen-preferential genes. Then, we performed a meta-expression analysis of all OsCNGC genes in anatomical samples and identified three pollen-preferred OsCNGCs (OsCNGC4, OsCNGC5, and OsCNGC8). The subcellular localization of these OsCNGC proteins is matched with their roles as ion channels on the plasma membrane. Unlike other OsCNGCs, these genes have a unique cis-acting element in the promoter. OsCNGC4 can act by forming a homomeric complex or a heteromeric complex with OsCNGC5 or OsCNGC8. In addition, it was suggested that they can form a multi-complex with Mildew Resistance Locus O (MLO) protein or other types of ion transporters, and that their expression can be modulated by Ruptured Pollen tube (RUPO) encoding receptor-like kinase. These results shed light on understanding the regulatory mechanisms of pollen germination and pollen tube growth through calcium channels in rice.

13.
Rice (N Y) ; 15(1): 39, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35859217

RESUMO

Understanding pollen tube growth is critical for crop yield maintenance. The pollen tube provides a path for sperm cells for fertilization with egg cells. Cells must be subdivided into functionally and structurally distinct compartments for polar tip growth, and phosphoinositides are thought to be one of the facilitators for polarization during pollen tube growth. OsSNDP3 encodes Sec14-nodulin domain-containing protein and localizes in the nucleus and the microdomains of the plasma membrane in tobacco leaf epidermis cells. OsSNDP3 is thought to bind with phosphatidylinositol 4,5-bisphosphate based on the data including the information of basic amino acids in the C-terminal and colocalization with 2X Pleckstrin homology domain of Phospholipase C delta-1. OsSNDP3 interacts with a protein that contains a class I nodulin domain. We discovered that OsSNDP3 plays a significant role in pollen tube germination using CRISPR/Cas9 systems, whereas another pollen-preferential Sec14-nodulin domain-containing protein, OsSNDP2, additively functions with OsSNDP3 during pollen tube germination. Gene Ontology analysis using downregulated genes in ossndp3 indicated that the expression of genes involved in the phosphatidylinositol metabolic process and tip growth was significantly altered in ossndp3. OsSNDP3 aids pollen polar tip growth by binding with phosphatidylinositol 4,5-bisphosphate. We can better understand the roles of phosphoinositides during pollen tube growth by studying the functions of OsSNDP3 and OsSNDP2. And downregulated genes in ossndp3 might be useful targets for future research on polar tip growth.

14.
ACS Biomater Sci Eng ; 8(7): 2878-2889, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35658391

RESUMO

Surface plasmon resonance (SPR) phenomena have been widely studied to detect biomolecules because of their high sensitivity and ability to determine biomolecular interactions with kinetic information. However, highly selective detection in specific concentration ranges relevant to target biomolecules is still a challenging task. Recently, we developed bioresponsive nanoscale hydrogels to selectively intensify SPR signals through multivalent protein binding (MPB) events with target biomolecules, including IL-2, where we were able to demonstrate exceptional selectivity for target biomolecules with minimal responses to nonspecific and monovalent binding events. In this work, we systematically explored the relationship between the physical properties of MPB-capable nanoscale hydrogels and their SPR response induced in the presence of the programmed cell death protein 1 antibody (PD-1Ab) as a model target biomolecule. First, we developed a synthetic protocol by controlling various reaction parameters to construct a library of nanoscale poly(N-isopropylacrylamide-co-acrylic acid) hydrogels (NHs) with different sizes (from 400 nm to 1 µm) and degrees of crosslinking (from 2 to 8%). Then, by incorporating MPB-capable PD-1 receptors onto the surface of NHs to form PD-1-responsive nanoscale hydrogels (PNHs), the hydrogel size and crosslinking dependency of their SPR responses were investigated. Our results reveal the appropriate hydrogel size regime and degree of crosslinking for effective PD-1Ab detection at specific concentrations range between a few nM and 1 µM. Overall, our study demonstrates that by tuning the physical properties of the nanoscale hydrogel matrix, the sensitivity and detection range of MPB-based SPR sensors can be modulated to potentially benefit clinical applications such as monitoring diverse therapeutic biomolecules.


Assuntos
Hidrogéis , Ressonância de Plasmônio de Superfície , Hidrogéis/química , Receptor de Morte Celular Programada 1 , Ligação Proteica , Ressonância de Plasmônio de Superfície/métodos
15.
Plant Cell Rep ; 41(5): 1229-1242, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35249124

RESUMO

To further understand the regulatory mechanism for anther dehiscence in rice, we carried out transcriptome analysis for the following two tissues: the anther wall and pollen at the anthesis stage. With the anatomical meta-expression data, in addition to these tissues, the differentially expressed genes (DEGs) between the two tissues were further refined to identify 1,717 pollen-preferred genes and 534 anther wall-preferred genes. A GUS transgenic line and RT-qPCR analysis for anther wall-preferred genes supported the fidelity of our gene candidates for further analysis. The refined DEGs were functionally classified through Gene Ontology (GO) enrichment and MapMan analyses. Through the analysis of cis-acting elements and alternative splicing variants, we also suggest the feature of regulatory sequences in promoter regions for anther wall-preferred expression and provide information of the unique splicing variants in anther wall. Subsequently, it was found that hormone signaling and the resulting transcriptional regulation pathways may play an important role in anther dehiscence and anther wall development. Our results could provide useful insights into future research to broaden the molecular mechanism of anther dehiscence or anther wall development in rice.


Assuntos
Oryza , Flores , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/metabolismo
16.
Front Plant Sci ; 12: 609473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927731

RESUMO

Pollen in angiosperms plays a critical role in double fertilization by germinating and elongating pollen tubes rapidly in one direction to deliver sperm. In this process, the secretory vesicles deliver cell wall and plasma membrane materials, and excessive materials are sequestered via endocytosis. However, endocytosis in plants is poorly understood. AP180 N-terminal homology (ANTH) domain-containing proteins function as adaptive regulators for clathrin-mediated endocytosis in eukaryotic systems. Here, we identified 17 ANTH domain-containing proteins from rice based on a genome-wide investigation. Motif and phylogenomic analyses revealed seven asparagine-proline-phenylalanine (NPF)-rich and 10 NPF-less subgroups of these proteins, as well as various clathrin-mediated endocytosis-related motifs in their C-terminals. To investigate their roles in pollen germination, we performed meta-expression analysis of all genes encoding ANTH domain-containing proteins in Oryza sativa (OsANTH genes) in anatomical samples, including pollen, and identified five mature pollen-preferred OsANTH genes. The subcellular localization of four OsANTH proteins that were preferentially expressed in mature pollen can be consistent with their role in endocytosis in the plasma membrane. Of them, OsANTH3 represented the highest expression in mature pollen. Functional characterization of OsANTH3 using T-DNA insertional knockout and gene-edited mutants revealed that a mutation in OsANTH3 decreased seed fertility by reducing the pollen germination percentage in rice. Thus, our study suggests OsANTH3-mediated endocytosis is important for rice pollen germination.

17.
Ann Neurol ; 89(3): 444-458, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33219556

RESUMO

OBJECTIVE: It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. METHODS: Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. RESULTS: We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. INTERPRETATION: We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.


Assuntos
Antitrombinas/efeitos adversos , Trombose das Artérias Carótidas/diagnóstico por imagem , Dabigatrana/efeitos adversos , Desprescrições , Agregação Plaquetária/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/sangue , Trombofilia/sangue , Idoso , Idoso de 80 Anos ou mais , Animais , Antitrombinas/farmacologia , Ácido Araquidônico/sangue , Aspirina/farmacologia , Trombose das Artérias Carótidas/induzido quimicamente , Trombose das Artérias Carótidas/prevenção & controle , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Infarto Cerebral/fisiopatologia , Infarto Cerebral/prevenção & controle , Cloretos/toxicidade , Angiografia por Tomografia Computadorizada , Dabigatrana/farmacologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Compostos Férricos/toxicidade , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/prevenção & controle , Angiografia por Ressonância Magnética , Masculino , Volume Plaquetário Médio , Camundongos , Noxas/toxicidade , Projetos Piloto , Inibidores da Agregação Plaquetária/farmacologia , Contagem de Plaquetas , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Trombina/metabolismo , Trombofilia/etiologia , Trombofilia/prevenção & controle , Microtomografia por Raio-X
18.
Anesth Pain Med (Seoul) ; 15(1): 19-27, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33329785

RESUMO

BACKGROUND: Bile duct ligation (BDL) has been used for experimental research on hepatic encephalopathy (HE) caused by chronic liver disease. However, little research has been done on a BDL model in C57BL/6 mouse. Therefore, we evaluated the suitability of a BDL model in C57BL/6 mouse for the study of HE and determined which behavioral tests are appropriate for the identification of HE in this model. METHODS: Twelve to fourteen-week-old male C57BL/6 mice were randomly assigned to either sham group or BDL group. Histological changes in liver were confirmed by hematoxylin/eosin and Masson's trichrome staining. Liver function alterations were detected by alanine aminotransferase (ALT) and ammonia levels. To identify behavioral changes, open field, elevated plus maze, novel object recognition, and passive avoidance tests were performed. RESULTS: Inflammatory liver injury and fibrosis were observed 14 days after BDL. ALT and ammonia levels were significantly higher in BDL group than in sham group. There were no differences in general locomotor activity or anxiety between the groups. No difference was observed between these two groups in the novel object recognition test, but BDL group showed significant learning/memory impairment in the passive avoidance test compared to sham group. CONCLUSIONS: Fourteen days of BDL in 12-14-week-old male C57BL/6 mice is a clinically relevant model for HE, as these mice have liver fibrosis with impaired liver function, hyperammonemia, and learning/memory impairment. Passive avoidance can be used as the major behavioral test in this model of HE.

19.
PLoS One ; 15(7): e0234415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673322

RESUMO

BACKGROUND: Discrimination is associated with depressive symptoms and other negative health effects, but little is known about the mental health risks of workplace gender discrimination. We aimed to investigate the association of workplace gender discrimination and depressive symptoms among employed women in South Korea. METHODS: The 6th wave (2016) survey datasets of the Korean Longitudinal Survey of Women and Family (KLoWF) were analyzed for 2,339 respondents who are identified as wage workers. Depressive symptoms were evaluated by the short-form (10-item) Center for Epidemiological Studies-Depression scale. Association of workplace gender discrimination and depressive symptoms was assessed using multivariate logistic regression, adjusted for potential confounding variables including age, income satisfaction, education level, marital status, and currently diagnosed disease. We then measured the age effect using age stratification multivariate logistic regression model. RESULTS: Women who experienced gender discrimination at workplace had higher odds of depressive symptoms regardless of the type of the discrimination including hiring, promotion, work assignments, paid wages, and firing. These associations were consistent in younger women below 40 years of age in regard to hiring, promotion, paid wages and firing, whereas inconsistent among older women above 40 years of age. LIMITATIONS: We did not investigate the effect of workplace gender discrimination on depressive symptoms in a longitudinal manner. CONCLUSIONS: Workplace gender discrimination was found to be significantly associated with depressive symptoms after adjustment for socio-demographic factors. Further, women under 40 years of age were especially vulnerable to workplace gender discrimination.


Assuntos
Bullying/psicologia , Depressão/psicologia , Sexismo/psicologia , Adulto , Estudos Transversais , Depressão/etiologia , Emprego , Feminino , Humanos , Modelos Logísticos , Estado Civil , Pessoa de Meia-Idade , Razão de Chances , Satisfação Pessoal , República da Coreia , Salários e Benefícios , Sexismo/ética , Inquéritos e Questionários , Local de Trabalho/psicologia
20.
J Affect Disord ; 274: 768-773, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32664013

RESUMO

BACKGROUND: Depression in adolescence is a social problem that has detrimental effects on an individual's physical and mental health and increases health care burden on families and society. This study investigates the connection between mental illness among parents and their adolescent children in Korea. METHODS: The sample included parents of 5315 adolescents (12-24 years) and data were obtained from the Korea National Health and Nutrition Survey (KNHANES) from 2007 to 2017. Family based comprehensive questionnaires were used. Multivariate logistic regression models were performed to estimate odds ratios (ORs) at 95% confidence intervals (95% CIs). RESULTS: The main findings showed that daughters with depressed mothers were 1.92 times more likely to experience depression and 1.64 times more likely to have suicidal ideations. In particular, when father was suicidal, his daughter had a 2.59 times higher risk of suicidal thoughts than father was not depressed and had no suicidal thoughts. Sons' depressive mood was rarely affected by the psychological status of mothers and fathers. LIMITATION: There are under-report issue of feelings and study design is cross-sectional. CONCLUSIONS: This study showed gender differences in the association between parents' and adolescents' experience of depression. Thus, the daughter's psychological state was found to be strongly associated with the psychological state of both parents.


Assuntos
Depressão , Ideação Suicida , Adolescente , Criança , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Saúde Mental , Pais , República da Coreia/epidemiologia
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