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1.
J Cancer Res Clin Oncol ; 150(5): 266, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769166

RESUMO

PURPOSE: Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs). However, real-world safety data for a more diverse population are needed, as carfilzomib received expedited approval. This study aimed to evaluate carfilzomib's safety in Korea by comparing new users of KRd (carfilzomib, lenalidomide, and dexamethasone) to Rd (lenalidomide and dexamethasone) using a nationwide administrative claims database. METHODS: The retrospective cohort study utilized target trial emulation, focusing on adverse events in various organ systems similar to the ASPIRE trial. RESULTS: This study included 4,580 RRMM patients between 2007 and 2020, and the KRd group showed significantly higher risks of hematologic adverse events (anemia, neutropenia, thrombocytopenia) and some non-hematologic adverse events (cough, hypokalemia, constipation, hypertension, heart failure) compared to the Rd group. Among non-hematologic adverse events, cardiovascular events (heart failure [HR 2.04; 95% CI 1.24-3.35], hypertension [HR 1.58; 95% CI 1.15-2.17]) had the highest risk in the KRd group. CONCLUSION: The safety profile of carfilzomib in Korean patients was similar to previous RCTs. Therefore, caution should be exercised when using carfilzomib in Asian individuals with RRMM due to the increased risk of cardiovascular adverse events.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiplo , Oligopeptídeos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Oligopeptídeos/administração & dosagem , Masculino , Feminino , República da Coreia/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Lenalidomida/efeitos adversos , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico
2.
Nat Plants ; 10(3): 494-511, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38467800

RESUMO

Pressurized cells with strong walls make up the hydrostatic skeleton of plants. Assembly and expansion of such stressed walls depend on a family of secreted RAPID ALKALINIZATION FACTOR (RALF) peptides, which bind both a membrane receptor complex and wall-localized LEUCINE-RICH REPEAT EXTENSIN (LRXs) in a mutually exclusive way. Here we show that, in root hairs, the RALF22 peptide has a dual structural and signalling role in cell expansion. Together with LRX1, it directs the compaction of charged pectin polymers at the root hair tip into periodic circumferential rings. Free RALF22 induces the formation of a complex with LORELEI-LIKE-GPI-ANCHORED PROTEIN 1 and FERONIA, triggering adaptive cellular responses. These findings show how a peptide simultaneously functions as a structural component organizing cell wall architecture and as a feedback signalling molecule that regulates this process depending on its interaction partners. This mechanism may also underlie wall assembly and expansion in other plant cell types.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/química , Arabidopsis/metabolismo , Peptídeos/metabolismo , Plantas/metabolismo , Parede Celular/metabolismo , Raízes de Plantas/metabolismo
3.
Cancer Immunol Res ; 12(4): 491-507, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38289363

RESUMO

The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non-small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame the limitations of first-generation immune-checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti-PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoglobulinas , Neoplasias Pulmonares , Proteínas de Membrana , Animais , Humanos , Camundongos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoglobulinas/metabolismo , Imunoterapia , Leucócitos Mononucleares , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo
4.
Ecotoxicol Environ Saf ; 269: 115820, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103469

RESUMO

Perfluorooctanesulfonate (PFOS) is a ubiquitous environmental pollutant associated with increasing health concerns and environmental hazards. Toxicological analyses of PFOS exposure are hampered by large interspecies variations and limited studies on the mechanistic details of PFOS-induced toxicity. We investigated the effects of PFOS exposure on Xenopus laevis embryos based on the reported developmental effects in zebrafish. X. laevis was selected to further our understanding of interspecies variation in response to PFOS, and we built upon previous studies by including transcriptomics and an assessment of ciliogenic effects. Midblastula-stage X. laevis embryos were exposed to PFOS using the frog embryo teratogenesis assay Xenopus (FETAX). Results showed teratogenic effects of PFOS in a time- and dose-dependent manner. The morphological abnormalities of skeleton deformities, a small head, and a miscoiled gut were associated with changes in gene expression evidenced by whole-mount in situ hybridization and transcriptomics. The transcriptomic profile of PFOS-exposed embryos indicated the perturbation in the expression of genes associated with cell death, and downregulation in adenosine triphosphate (ATP) biosynthesis. Moreover, we observed the effects of PFOS exposure on cilia development as a reduction in the number of multiciliated cells and changes in the directionality and velocity of the cilia-driven flow. Collectively, these data broaden the molecular understanding of PFOS-induced developmental effects, whereby ciliary dysfunction and disrupted ATP synthesis are implicated as the probable modes of action of embryotoxicity. Furthermore, our findings present a new challenge to understand the links between PFOS-induced developmental toxicity and vital biological processes.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Perfilação da Expressão Gênica , Peixe-Zebra , Animais , Xenopus laevis/genética , Trifosfato de Adenosina , Embrião não Mamífero , Teratogênicos/toxicidade
5.
Dev Reprod ; 27(3): 159-165, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38074458

RESUMO

The Ruvb-like AAA ATPase1 (Ruvbl1; also known as Pontin) is an evolutionary conserved protein belonging to the adenosine triphosphates associated with diverse cellular activities (AAA+) superfamily of ATPases. Ruvbl1 is a component of various protein supercomplexes and is involved in a variety of cellular activities, including chromatin remodeling, DNA damage repair, and mitotic spindle assembly however, the developmental significance of this protein is unknown and needs detailed investigation. We investigated the developmental significance of Ruvbl1 in multiciliated cells of the Xenopus laevis epidermis since ruvbl1 is expressed in the multiciliated cells and pronephros during X. laevis embryogenesis. The knockdown of ruvbl1 significantly impaired cilia-driven fluid flow and basal body polarity in the X. laevis epidermis compared to control embryos, but did not affect cilia morphology. Our results suggest that Ruvbl1 plays a significant role in embryonic development by regulating ciliary beating; however, further investigation is needed to determine the mechanisms involved.

6.
Science ; 382(6671): 719-725, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37943924

RESUMO

Assembly of cell wall polysaccharides into specific patterns is required for plant growth. A complex of RAPID ALKALINIZATION FACTOR 4 (RALF4) and its cell wall-anchored LEUCINE-RICH REPEAT EXTENSIN 8 (LRX8)-interacting protein is crucial for cell wall integrity during pollen tube growth, but its molecular connection with the cell wall is unknown. Here, we show that LRX8-RALF4 complexes adopt a heterotetrametric configuration in vivo, displaying a dendritic distribution. The LRX8-RALF4 complex specifically interacts with demethylesterified pectins in a charge-dependent manner through RALF4's polycationic surface. The LRX8-RALF4-pectin interaction exerts a condensing effect, patterning the cell wall's polymers into a reticulated network essential for wall integrity and expansion. Our work uncovers a dual structural and signaling role for RALF4 in pollen tube growth and in the assembly of complex extracellular polymers.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Parede Celular , Pectinas , Tubo Polínico , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Parede Celular/química , Parede Celular/metabolismo , Pectinas/química , Pectinas/metabolismo , Peptídeos/metabolismo , Tubo Polínico/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo
7.
J Pers Med ; 13(8)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37623492

RESUMO

Interstitial fibrosis and tubular atrophy (IF/TA) after kidney transplantation causes a chronic deterioration of graft function. IF/TA can be diagnosed by means of a graft biopsy, which is a necessity as non-invasive diagnostic methods are unavailable. In this study, we identified IF/TA-related differentially expressed genes (DEGs) through next-generation sequencing using peripheral blood mononuclear cells. Blood samples from kidney transplant recipients undergoing standard immunosuppressive therapy (tacrolimus/mycophenolate mofetil or mycophenolate sodium/steroid) and diagnosed as IF/TA (n = 41) or normal (controls; n = 41) at their one-year protocol biopsy were recruited between January of 2020 and August of 2020. DEGs were derived through mRNA sequencing and validated by means of a quantitative real-time polymerase chain reaction. We identified 34 DEGs related to IF/TA. ADAMTS2, PLIN5, CLDN9, and KCNJ15 demonstrated a log2(fold change) of >1.5 and an area under the receiver operating characteristic curve (AUC) value of >0.6, with ADAMTS2 showing the largest AUC value and expression levels, which were 3.5-fold higher in the IF/TA group relative to that observed in the control group. We identified and validated DEGs related to IF/TA progression at one-year post-transplantation. Specifically, we identified ADAMTS2 as a potential IF/TA biomarker.

8.
BMC Med Ethics ; 24(1): 52, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37461075

RESUMO

BACKGROUND: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. METHODS: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan-Meier curve analyses for survival were performed. RESULTS: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63-81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan-Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). CONCLUSIONS: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.


Assuntos
Neoplasias , Pneumonia , Humanos , Idoso de 80 Anos ou mais , Idoso , Estudos Retrospectivos , Tomada de Decisões , Ordens quanto à Conduta (Ética Médica) , Suspensão de Tratamento , Hospitais , Pneumonia/terapia , República da Coreia/epidemiologia , Morte
9.
Artigo em Inglês | MEDLINE | ID: mdl-36294140

RESUMO

Carfilzomib is a promising anticancer drug for relapsed/refractory multiple myeloma (RRMM). However, real-world evidence has only investigated the cardiovascular safety of carfilzomib, and there is a high demand for thorough safety evaluations. We aimed to comprehensively evaluate the risk of adverse events associated with carfilzomib in Korean patients with RRMM. We followed up with 138 matched patients with RRMM (69 KRd (carfilzomib, lenalidomide, and dexamethasone) and 69 Rd (lenalidomide and dexamethasone) users). A total of 12 adverse events were evaluated. More than 75% of adverse events occurred during the early cycle (1-6 cycles), and the incidence rate showed a tendency to decrease in the later cycle (7-12 and 13-18 cycles). Severities of most adverse events were evaluated as grade 1-2. The KRd regimen were related with significantly increased risks of dyspnea (adjusted HR (aHR) 2.27, 95% confidence interval (CI) 1.24-4.16), muscle spasm (aHR 5.12, 95% CI 1.05-24.9) and thrombocytopenia (aHR 1.84, 95% CI 1.10-3.06). Although the severities were low, carfilzomib has many side effects in treating RRMM; hence, findings on the patterns of its adverse events could lead to both effective and safe use of KRd therapy in real-world settings.


Assuntos
Antineoplásicos , Mieloma Múltiplo , Humanos , Lenalidomida/uso terapêutico , Registros Eletrônicos de Saúde , Dexametasona , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/induzido quimicamente , Antineoplásicos/efeitos adversos
10.
Sci Rep ; 12(1): 15605, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114344

RESUMO

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.


Assuntos
Fragilidade , Pneumonia Associada a Assistência à Saúde , Desnutrição , Idoso , Exercício Físico , Fragilidade/complicações , Avaliação Geriátrica , Hospitais , Humanos , Desnutrição/etiologia
11.
Korean J Intern Med ; 37(4): 800-810, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35811368

RESUMO

BACKGROUND/AIMS: Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea. METHODS: This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups. RESULTS: Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007). CONCLUSION: The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.


Assuntos
Infecção Hospitalar , Pneumonia , Antibacterianos/uso terapêutico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas , Humanos , Unidades de Terapia Intensiva , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Pneumonia/epidemiologia , Sistema de Registros , Estudos Retrospectivos
12.
Thorac Cancer ; 13(15): 2170-2179, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35785522

RESUMO

BACKGROUND: Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement. METHODS: This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software. RESULTS: A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv. CONCLUSIONS: There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos
13.
Thorac Cancer ; 13(13): 1998-2000, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35599247

RESUMO

Highly active and durable systemic therapies such as targeted therapy and immunotherapy can convert widespread metastatic disease into oligometastatic status, for which metastasis-directed local intervention can control and potentially prolong survival. Radiation therapy is an effective therapeutic option for oligometastatic and oligoprogressive disease. Here, we present a case of induced oligometastasis and repeated oligoprogressive lung cancer in which more than 6 years of survival was achieved with a combination of immunotherapy and radiotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Radiocirurgia , Adenocarcinoma de Pulmão/radioterapia , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia
14.
Cell Rep ; 38(5): 110312, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35108539

RESUMO

The Zic family of zinc finger transcription factors plays a critical role in multiple developmental processes. Using loss-of-function studies, we find that Zic5 is important for the differentiation of retinal pigmented epithelium (RPE) and the rod photoreceptor layer through suppressing Hedgehog (Hh) signaling. Further, Zic5 interacts with the critical Hh signaling molecule, Gli3, through the zinc finger domains of both proteins. This Zic5-Gli3 interaction disrupts Gli3/Gli3 homodimerization, resulting in Gli3 protein stabilization via a reduction in Gli3 ubiquitination. During embryonic Hh signaling, the activator form of Gli is normally converted to a repressor form through proteosome-mediated processing of Gli3, and the ratio of Gli3 repressor to full-length (activator) form of Gli3 determines the Gli3 repressor output required for normal eye development. Our results suggest Zic5 is a critical player in regulating Gli3 stability for the proper differentiation of RPE and rod photoreceptor layer during Xenopus eye development.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Retina/crescimento & desenvolvimento , Proteínas de Xenopus/metabolismo , Proteína Gli3 com Dedos de Zinco/metabolismo , Animais , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Xenopus
15.
Plant Physiol ; 188(4): 2073-2084, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35078230

RESUMO

Successful reproduction in the Brassicaceae is mediated by a complex series of interactions between the pollen and the pistil, and some species have an additional layer of regulation with the self-incompatibility trait. While the initial activation of the self-incompatibility pathway by the pollen S-locus protein 11/S locus cysteine-rich protein and the stigma S Receptor Kinase is well characterized, the downstream mechanisms causing self-pollen rejection are still not fully understood. In previous studies, we detected the presence of autophagic bodies with self-incompatible (SI) pollinations in Arabidopsis lyrata and transgenic Arabidopsis thaliana lines, but whether autophagy was essential for self-pollen rejection was unknown. Here, we investigated the requirement of autophagy in this response by crossing mutations in the essential AUTOPHAGY7 (ATG7) and ATG5 genes into two different transgenic SI A. thaliana lines in the Col-0 and C24 accessions. By using these previously characterized transgenic lines that express A. lyrata and Arabidopsis halleri self-incompatibility genes, we demonstrated that disrupting autophagy weakened their SI responses in the stigma. When the atg7 or atg5 mutations were present, an increased number of SI pollen was found to hydrate and form pollen tubes that successfully fertilized the SI pistils. Additionally, we confirmed the presence of GFP-ATG8a-labeled autophagosomes in the stigmatic papillae following SI pollinations. Together, these findings support the requirement of autophagy in the self-incompatibility response and add to the growing understanding of the intracellular mechanisms employed in the transgenic A. thaliana stigmas to reject self-pollen.


Assuntos
Arabidopsis , Arabidopsis/genética , Autofagia/genética , Pólen/metabolismo , Tubo Polínico , Polinização/genética
16.
J Cell Biol ; 221(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34787650

RESUMO

Proper cilia formation in multiciliated cells (MCCs) is necessary for appropriate embryonic development and homeostasis. Multicilia share many structural characteristics with monocilia and primary cilia, but there are still significant gaps in our understanding of the regulation of multiciliogenesis. Using the Xenopus embryo, we show that CEP97, which is known as a negative regulator of primary cilia formation, interacts with dual specificity tyrosine phosphorylation regulated kinase 1A (Dyrk1a) to modulate multiciliogenesis. We show that Dyrk1a phosphorylates CEP97, which in turn promotes the recruitment of Polo-like kinase 1 (Plk1), which is a critical regulator of MCC maturation that functions to enhance centriole disengagement in cooperation with the enzyme Separase. Knockdown of either CEP97 or Dyrk1a disrupts cilia formation and centriole disengagement in MCCs, but this defect is rescued by overexpression of Separase. Thus, our study reveals that Dyrk1a and CEP97 coordinate with Plk1 to promote Separase function to properly form multicilia in vertebrate MCCs.


Assuntos
Centríolos/metabolismo , Cílios/metabolismo , Proteínas do Citoesqueleto/metabolismo , Organogênese , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas de Xenopus/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Proteínas do Citoesqueleto/química , Embrião não Mamífero/metabolismo , Embrião não Mamífero/ultraestrutura , Humanos , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/química , Proteínas Tirosina Quinases/química , Proteínas Proto-Oncogênicas/metabolismo , Especificidade por Substrato , Xenopus , Proteínas de Xenopus/química , Quinase 1 Polo-Like
17.
Membranes (Basel) ; 11(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34564525

RESUMO

In this study, we mixed the zeolitic imidazolate framework-7 (ZIF-7) with poly(ether-b-amide)® 2533 (Pebax-2533) and used it as a selective layer for a composite membrane. We prepared the composite membrane's substrate using polysulfone (PSf), adjusted its pore size using polyethylene glycol (PEG), and applied polydimethylsiloxane (PDMS) to the gutter layer and the coating layer. Then, we investigated the membrane's properties of gases by penetrating a single gas (N2, CO2) into the membrane. We identified the peaks and geometry of ZIF-7 to determine if it had been successfully synthesized. We confirmed that ZIF-7 had a BET surface area of 303 m2/g, a significantly high Langmuir surface area of 511 m2/g, and a high CO2/N2 adsorption selectivity of approximately 50. Considering the gas permeation, with ZIF-7 mixed into Pebax-2533, N2 permeation decreased from 2.68 GPU in a pure membrane to 0.43 GPU in the membrane with ZIF-7 25 wt%. CO2 permeation increased from 18.43 GPU in the pure membrane to 26.22 GPU in the ZIF-7 35 wt%. The CO2/N2 ideal selectivity increased from 6.88 in the pure membrane to 50.43 in the ZIF-7 25 wt%. Among the membranes, Pebax-2533/ZIF-7 25 wt% showed the highest permeation properties and the characteristics of CO2-friendly ZIF-7.

18.
Antioxidants (Basel) ; 10(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34439449

RESUMO

The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and ß-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34207330

RESUMO

BACKGROUND: This study aimed to evaluate the successful smoking cessation across different national smoking cessation services. METHODS: This study included data that had been previously entered into the integrated information system for smoking cessation services and comprised 144,688 participants after excluding missing data. These clinics provide face-to-face counseling, phone calls, text messages, and e-mail services for six months and nine sessions. RESULTS: The women-only program had the lowest success rate (11.3%). Compared with the women-only program, the six-month success rate of smoking cessation clinic at public health centers (OR = 3.72, CI = [3.52, 3.92]), visiting-type smoking cessation clinics (OR = 2.97, CI = [2.79, 3.16]), the residential 4 -night 5-day program (OR = 7.79, CI = [6.49, 9.35]), and a program for inpatients (OR = 2.36, CI = [1.89, 2.94]) showed a significant increase. CONCLUSIONS: Emotional labor workers who participated in the women-only program had low smoking cessation success rates, while those who participated in the residential 4-night 5-day program had high success rates.


Assuntos
Abandono do Hábito de Fumar , Envio de Mensagens de Texto , Aconselhamento , Feminino , Humanos , República da Coreia/epidemiologia , Fumantes
20.
Artigo em Inglês | MEDLINE | ID: mdl-34067704

RESUMO

Despite the steadily increasing prevalence of female smoking, gender-responsive tobacco cessation services have not been widely provided worldwide. The purpose of this study is to identify factors associated with the use of tobacco cessation services among female tobacco product users in Korea from a national perspective. We performed a logistic regression analysis using data from 663 female smokers; 11.0% of female smokers had used government-supported smoking cessation services. A logistic regression model showed a statistically significant association between the utilization of smoking cessation services and a history of pregnancy and childbirth, depression, current use of heated tobacco products and multiple tobacco products, parental smoking status and receiving advice to quit. With regard to the motivation ruler, those in their 50s reported a higher importance than those in their 20s. Weight gain concerns when quitting smoking were the lowest among the participants aged 19-29. The need to develop gender-specific smoking cessation programs is the highest among the participants aged 39-49 and the lowest among those aged 19-29. This study suggests several factors related to the utilization of national health services among female smokers. Further studies considering gender-specific needs for the development of gender-responsive tobacco cessation support are needed.


Assuntos
Abandono do Hábito de Fumar , Produtos do Tabaco , Abandono do Uso de Tabaco , Feminino , Humanos , República da Coreia/epidemiologia , Fumantes
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