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1.
Proc Natl Acad Sci U S A ; 120(4): e2210632120, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36669117

RESUMO

Plant cells are surrounded by a cell wall and do not migrate, which makes the regulation of cell division orientation crucial for development. Regulatory mechanisms controlling cell division orientation may have contributed to the evolution of body organization in land plants. The GRAS family of transcription factors was transferred horizontally from soil bacteria to an algal common ancestor of land plants. SHORTROOT (SHR) and SCARECROW (SCR) genes in this family regulate formative periclinal cell divisions in the roots of flowering plants, but their roles in nonflowering plants and their evolution have not been studied in relation to body organization. Here, we show that SHR cell autonomously inhibits formative periclinal cell divisions indispensable for leaf vein formation in the moss Physcomitrium patens, and SHR expression is positively and negatively regulated by SCR and the GRAS member LATERAL SUPPRESSOR, respectively. While precursor cells of a leaf vein lacking SHR usually follow the geometry rule of dividing along the division plane with the minimum surface area, SHR overrides this rule and forces cells to divide nonpericlinally. Together, these results imply that these bacterially derived GRAS transcription factors were involved in the establishment of the genetic regulatory networks modulating cell division orientation in the common ancestor of land plants and were later adapted to function in flowering plant and moss lineages for their specific body organizations.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Divisão Celular/genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
2.
New Phytol ; 241(2): 665-675, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37865886

RESUMO

Anisotropic cell expansion is crucial for the morphogenesis of land plants, as cell migration is restricted by the rigid cell wall. The anisotropy of cell expansion is regulated by mechanisms acting on the deposition or modification of cell wall polysaccharides. Besides the polysaccharide components in the cell wall, a layer of hydrophobic cuticle covers the outer cell wall and is subjected to tensile stress that mechanically restricts cell expansion. However, the molecular machinery that deposits cuticle materials in the appropriate spatiotemporal manner to accommodate cell and tissue expansion remains elusive. Here, we report that PpABCB14, an ATP-binding cassette transporter in the moss Physcomitrium patens, regulates the anisotropy of cell expansion. PpABCB14 localized to expanding regions of leaf cells. Deletion of PpABCB14 resulted in impaired anisotropic cell expansion. Unexpectedly, the cuticle proper was reduced in the mutants, and the cuticular lipid components decreased. Moreover, induced PpABCB14 expression resulted in deformed leaf cells with increased cuticle lipid accumulation on the cell surface. Taken together, PpABCB14 regulates the anisotropy of cell expansion via cuticle deposition, revealing a regulatory mechanism for cell expansion in addition to the mechanisms acting on cell wall polysaccharides.


Assuntos
Bryopsida , Bryopsida/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Folhas de Planta/metabolismo , Polissacarídeos/metabolismo , Lipídeos
3.
Opt Express ; 32(6): 10599-10617, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571267

RESUMO

In this paper, we have proposed a method of three-dimensional (3D) fluorescence imaging through a scattering medium. The proposed method combines the numerical digital phase conjugation propagation after measurement of the complex amplitude distribution of scattered light waves by the transport of intensity equation (TIE) with followed iterative phase retrieval to achieve 3D fluorescence imaging through a scattering medium. In the experiment, we present the quantitative evaluation of the depth position of fluorescent beads. In addition, for time-lapse measurement, cell division of tobacco-cultured cells was observed. Numerical results presented the effective range of the phase amount in the scattering medium. From these results, the proposed method is capable of recovering images degraded by a thin scattering phase object beyond a small phase change approximation.

4.
Diabetes Obes Metab ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764356

RESUMO

AIM: To conduct a post hoc subgroup analysis of patients with type 2 diabetes (T2D) from the RECAP study, who were treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor and glucagon-like peptide 1 receptor agonist (GLP-1RA) combination therapy, focusing only on those patients who had chronic kidney disease (CKD), to examine whether the composite renal outcome differed between those who received SGLT2 inhibitor treatment first and those who received a GLP-1RA first. METHODS: We included 438 patients with CKD (GLP-1RA-first group, n = 223; SGLT2 inhibitor-first group, n = 215) from the 643 T2D patients in the RECAP study. The incidence of the composite renal outcome, defined as progression to macroalbuminuria and/or a ≥50% decrease in estimated glomerular filtration rate (eGFR), was analysed using a propensity score (PS)-matched model. Furthermore, we calculated the win ratio for these composite renal outcomes, which were weighted in the following order: (1) both a ≥50% decrease in eGFR and progression to macroalbuminuria; (2) a decrease in eGFR of ≥50% only; and (3) progression to macroalbuminuria only. RESULTS: Using the PS-matched model, 132 patients from each group were paired. The incidence of renal composite outcomes did not differ between the two groups (GLP-1RA-first group, 10%; SGLT2 inhibitor-first group, 17%; odds ratio 1.80; 95% confidence interval [CI] 0.85 to 4.26; p = 0.12). The win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was 1.83 (95% CI 1.71 to 1.95; p < 0.001). CONCLUSION: Although the renal composite outcome did not differ between the two groups, the win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was significant. These results suggest that, in GLP-1RA and SGLT2 inhibitor combination therapy, the addition of an SGLT2 inhibitor to baseline GLP-1RA treatment may lead to more favourable renal outcomes.

5.
Sensors (Basel) ; 24(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38339437

RESUMO

Quantitative phase imaging by digital holographic microscopy (DHM) is a nondestructive and label-free technique that has been playing an indispensable role in the fields of science, technology, and biomedical imaging. The technique is competent in imaging and analyzing label-free living cells and investigating reflective surfaces. Herein, we introduce a new configuration of a wide field-of-view single-shot common-path off-axis reflective DHM for the quantitative phase imaging of biological cells that leverages several advantages, including being less-vibration sensitive to external perturbations due to its common-path configuration, also being compact in size, simple in optical design, highly stable, and cost-effective. A detailed description of the proposed DHM system, including its optical design, working principle, and capability for phase imaging, is presented. The applications of the proposed system are demonstrated through quantitative phase imaging results obtained from the reflective surface (USAF resolution test target) as well as transparent samples (living plant cells). The proposed system could find its applications in the investigation of several biological specimens and the optical metrology of micro-surfaces.


Assuntos
Holografia , Holografia/métodos , Imageamento Quantitativo de Fase
6.
BMC Urol ; 21(1): 8, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413292

RESUMO

BACKGROUND: Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. CASE PRESENTATION: A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. CONCLUSIONS: We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.


Assuntos
Adenocarcinoma/complicações , Dermatomiosite/complicações , Neoplasias da Próstata/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Dermatomiosite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
7.
Nucleic Acids Res ; 47(9): 4539-4553, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30873540

RESUMO

Next-generation sequencing technologies have made it possible to carry out transcriptome analysis at the single-cell level. Single-cell RNA-sequencing (scRNA-seq) data provide insights into cellular dynamics, including intercellular heterogeneity as well as inter- and intra-cellular fluctuations in gene expression that cannot be studied using populations of cells. The utilization of scRNA-seq is, however, restricted to cell types that can be isolated from their original tissues, and it can be difficult to obtain precise positional information for these cells in situ. Here, we established single cell-digital gene expression (1cell-DGE), a method of scRNA-seq that uses micromanipulation to extract the contents of individual living cells in intact tissue while recording their positional information. With 1cell-DGE, we could detect differentially expressed genes (DEGs) during the reprogramming of leaf cells of the moss Physcomitrella patens, identifying 6382 DEGs between cells at 0 and 24 h after excision. Furthermore, we identified a subpopulation of reprogramming cells based on their pseudotimes, which were calculated using transcriptome profiles at 24 h. 1cell-DGE with microcapillary manipulation can be used to analyze the gene expression of individual cells without detaching them from their tightly associated tissues, enabling us to retain positional information and investigate cell-cell interactions.


Assuntos
Bryopsida/genética , Reprogramação Celular/genética , Perfilação da Expressão Gênica/métodos , Análise de Célula Única/métodos , Folhas de Planta/genética , Análise de Sequência de RNA/métodos , Software , Transcriptoma/genética
8.
Proc Natl Acad Sci U S A ; 114(42): E8847-E8854, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28973935

RESUMO

Proper orientation of the cell division axis is critical for asymmetric cell divisions that underpin cell differentiation. In animals, centrosomes are the dominant microtubule organizing centers (MTOC) and play a pivotal role in axis determination by orienting the mitotic spindle. In land plants that lack centrosomes, a critical role of a microtubular ring structure, the preprophase band (PPB), has been observed in this process; the PPB is required for orienting (before prophase) and guiding (in telophase) the mitotic apparatus. However, plants must possess additional mechanisms to control the division axis, as certain cell types or mutants do not form PPBs. Here, using live imaging of the gametophore of the moss Physcomitrella patens, we identified acentrosomal MTOCs, which we termed "gametosomes," appearing de novo and transiently in the prophase cytoplasm independent of PPB formation. We show that gametosomes are dispensable for spindle formation but required for metaphase spindle orientation. In some cells, gametosomes appeared reminiscent of the bipolar MT "polar cap" structure that forms transiently around the prophase nucleus in angiosperms. Specific disruption of the polar caps in tobacco cells misoriented the metaphase spindles and frequently altered the final division plane, indicating that they are functionally analogous to the gametosomes. These results suggest a broad use of transient MTOC structures as the spindle orientation machinery in plants, compensating for the evolutionary loss of centrosomes, to secure the initial orientation of the spindle in a spatial window that allows subsequent fine-tuning of the division plane axis by the guidance machinery.


Assuntos
Bryopsida/citologia , Citoplasma/metabolismo , Microtúbulos/metabolismo , Fuso Acromático/metabolismo , Actinas/genética , Actinas/metabolismo , Divisão Celular Assimétrica , Citoplasma/ultraestrutura , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Células Vegetais , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Prófase , Imagem com Lapso de Tempo/métodos , Nicotiana/citologia , Nicotiana/genética , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
9.
Jpn J Clin Oncol ; 48(5): 485-490, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635526

RESUMO

BACKGROUND: The role of radical prostatectomy in treating non-metastatic prostate cancer patients with high prostate-specific antigen levels remains unclear. We evaluated the feasibility and oncological outcomes of radical prostatectomy in non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. METHODS: This retrospective study included 31 patients who were diagnosed as very high-risk prostate cancer (clinical stage of any T, N0-1 M0 and PSA levels ≥50 ng/ml) and underwent radical prostatectomy either as a monotherapy or as a component of multimodal therapy (RP group). Surgery-related complications were investigated. Time to castration-resistant prostate cancer, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method. A total of 47 patients with very high-risk prostate cancer who were treated with androgen deprivation therapy without local therapy served as a control group (ADT group). Survivals were compared between RP group and ADT group in exploratory analyses. RESULTS: The median pretreatment prostate-specific antigen was 87 ng/ml and 100 ng/ml in the RP and ADT groups, respectively (P = 0.67). Surgical complications of Clavien-Dindo Grade 3 were documented in nine patients (29%). Ten-year castration-resistant prostate cancer-free, cancer-specific and overall survivals were 78%, 81% and 77% in RP group, respectively, and they were significantly better than those of ADT group (54%, P = 0.006; 54%, P = 0.006 and 38%, P < 0.001). Exploratory multivariate analysis identified radical prostatectomy as the only significant factor associated with a better cancer-specific survival (hazard ratio: 0.25, P = 0.006). CONCLUSIONS: Radical prostatectomy is feasible for non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Radical prostatectomy is a viable option for select patients with non-metastatic, very high-risk prostate cancer.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antígeno Prostático Específico/metabolismo , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Development ; 141(8): 1660-70, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24715456

RESUMO

Many differentiated plant cells can dedifferentiate into stem cells, reflecting the remarkable developmental plasticity of plants. In the moss Physcomitrella patens, cells at the wound margin of detached leaves become reprogrammed into stem cells. Here, we report that two paralogous P. patens WUSCHEL-related homeobox 13-like (PpWOX13L) genes, homologs of stem cell regulators in flowering plants, are transiently upregulated and required for the initiation of cell growth during stem cell formation. Concordantly, Δppwox13l deletion mutants fail to upregulate genes encoding homologs of cell wall loosening factors during this process. During the moss life cycle, most of the Δppwox13l mutant zygotes fail to expand and initiate an apical stem cell to form the embryo. Our data show that PpWOX13L genes are required for the initiation of cell growth specifically during stem cell formation, in analogy to WOX stem cell functions in seed plants, but using a different cellular mechanism.


Assuntos
Bryopsida/citologia , Bryopsida/genética , Genes de Plantas/genética , Folhas de Planta/citologia , Proteínas de Plantas/genética , Protoplastos/citologia , Células-Tronco/citologia , Sequência de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Bryopsida/crescimento & desenvolvimento , Proliferação de Células , Parede Celular/genética , Deleção de Genes , Regulação da Expressão Gênica de Plantas , Meristema/citologia , Meristema/crescimento & desenvolvimento , Dados de Sequência Molecular , Folhas de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Protoplastos/metabolismo , Regeneração , Células-Tronco/metabolismo , Regulação para Cima/genética , Zigoto/citologia , Zigoto/crescimento & desenvolvimento
11.
Heart Vessels ; 30(5): 682-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24906987

RESUMO

In-stent restenosis (ISR) has long remained as the major limitation of coronary stenting. The use of drug-eluting stent (DES) reduces the risk of repeat revascularization without an increase of death and myocardial infarction, compared to the standard bare metal stents. DES has also demonstrated markedly to reduce ISR for complex lesions. However, ISR after DES implantation still occurs and optimal treatment for ISR after DES has not been established. Herein, we report 3 cases with black hole restenosis confirmed by intravascular ultrasound at the site of overlapped DES and discuss potential mechanism and optimal strategy for this phenomenon.


Assuntos
Stents Farmacológicos/efeitos adversos , Oclusão de Enxerto Vascular/diagnóstico , Infarto do Miocárdio/cirurgia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Angiografia Coronária , Feminino , Seguimentos , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Reoperação , Sirolimo , Ultrassonografia de Intervenção
12.
Nihon Hinyokika Gakkai Zasshi ; 106(2): 95-102, 2015 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-26415359

RESUMO

PURPOSE: The guidelines on adrenal hemorrhage has not established in Japan. In this article, we discuss the management of adrenal hemorrhage. OBJECTS AND METHODS: We experienced 6 patients from November 2004 to September 2013 in The University of Tokyo Hospital and The Fraternity Memorial Hospital, and we searched 57 cases already reported in Japan by using Japan Medical Abstracts Society (http://search.jamas.or.jp/). So we analyzed total 63 adrenal hemorrhage cases in Japan. RESULTS: In 63 cases, 5 cases were performed TAE, 3 cases were performed emergent surgeries, 13 cases were managed conservatively and elective surgeries were performed in the other cases. 5 cases were fulfilled criteria for Hb < 10 g/dl and the maximum diameter of the hematoma > 10 cm. Of 5 cases, 4 cases were performed emergent hemostasis. CONCLUSIONS: Adrenal hemorrhages caused by metastatic tumor tend to be serious anemia. In addition, the most patients with adrenal hemorrhages, who had Hb < 10 g/dl and the maximum diameter of the hematoma > 10 cm, required immediate medical treatment, e.g. TAE or surgical hemostasis.


Assuntos
Doenças das Glândulas Suprarrenais/etiologia , Hemorragia/etiologia , Doenças das Glândulas Suprarrenais/patologia , Doenças das Glândulas Suprarrenais/cirurgia , Adulto , Feminino , Hemorragia/patologia , Hemorragia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Plant Cell ; 23(8): 2924-38, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21862705

RESUMO

During regeneration, differentiated plant cells can be reprogrammed to produce stem cells, a process that requires coordination of cell cycle reactivation with acquisition of other cellular characteristics. However, the factors that coordinate the two functions during reprogramming have not been determined. Here, we report a link between cell cycle reactivation and the acquisition of new cell-type characteristics through the activity of cyclin-dependent kinase A (CDKA) during reprogramming in the moss Physcomitrella patens. Excised gametophore leaf cells of P. patens are readily reprogrammed, initiate tip growth, and form chloronema apical cells with stem cell characteristics at their first cell division. We found that leaf cells facing the cut undergo CDK activation along with induction of a D-type cyclin, tip growth, and transcriptional activation of protonema-specific genes. A DNA synthesis inhibitor, aphidicolin, inhibited cell cycle progression but prevented neither tip growth nor protonemal gene expression, indicating that cell cycle progression is not required for acquisition of protonema cell-type characteristics. By contrast, treatment with a CDK inhibitor or induction of dominant-negative CDKA;1 protein inhibited not only cell cycle progression but also tip growth and protonemal gene expression. These findings indicate that cell cycle progression is coordinated with other cellular changes by the concomitant regulation through CDKA;1.


Assuntos
Bryopsida/fisiologia , Ciclo Celular/fisiologia , Desdiferenciação Celular/fisiologia , Quinases Ciclina-Dependentes/metabolismo , Afidicolina/farmacologia , Sequência de Bases , Bryopsida/citologia , Bryopsida/efeitos dos fármacos , Bryopsida/genética , Ciclo Celular/efeitos dos fármacos , Ciclina D/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/genética , DNA de Plantas/química , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica de Plantas/fisiologia , Dados de Sequência Molecular , Mutação , Folhas de Planta/citologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA , Células-Tronco/fisiologia , Fatores de Tempo , Ativação Transcricional/fisiologia
14.
Diabetol Int ; 15(1): 76-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264229

RESUMO

Introduction: Insulin degludec (degludec) is a basal insulin with a long duration of action. This post-marketing surveillance study monitored safety and glycemic control during use of degludec for 3 years in normal clinical practice in Japan. Materials and methods: This multicenter, open-label, observational study included patients with diabetes receiving degludec in Japan between 2013 and 2019. The primary outcome was incidence of adverse events occurring over 3 years of treatment. The pre-specified, secondary outcomes were severe hypoglycemic episodes and changes in HbA1c and fasting plasma glucose levels. Results: Of 4167 patients enrolled, 4022 were included in the safety assessments and 3918 in the assessments of glycemic control. Mean age was 58.9 years; 74.1% of patients had type 2 diabetes, and mean HbA1c at baseline was 8.7%. Adverse events and serious adverse events were observed in 19.1% and 8.9% of patients, respectively. Cardiac disorders and neoplasms were reported in 2.0% and 1.8% of patients, respectively, with the majority of these incidents reported as serious adverse events. Adverse drug reactions were seen in 8.0% of patients, mainly hypoglycemia. Hypoglycemic events were observed in 5.6% of patients, and severe hypoglycemic events in 1.7%. No serious allergic or injection-site reactions were seen. Respective changes (from baseline to 3 years' observation) in HbA1c and fasting plasma glucose levels were - 0.55% and - 36.3 mg/dL, and 19.6% of patients reached HbA1c < 7.0%. Conclusions: Using degludec for 3 years in normal clinical practice had a good safety and tolerability profile. Improvements in glycemic control were also seen. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00657-7.

15.
Diabetol Int ; 15(1): 109-116, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264231

RESUMO

Introduction: This study aimed to investigate the association between scan frequency and intermittently scanned continuous glucose monitoring (isCGM) metrics and to clarify the factors affecting scan frequency in adults with type 1 diabetes mellitus (T1D). Methods: We enrolled adults with T1D who used FreeStyle® Libre. Scan and self-monitoring of blood glucose (SMBG) frequency and CGM metrics from the past 90-day glucose data were collected. The receiver operating characteristic curve was plotted to obtain the optimal cutoff values of scan frequency for the target values of time in range (TIR), time above range (TAR), and time below range (TBR). Results: The study was conducted on 211 adults with T1D (mean age, 50.9 ± 15.2 years; male, 40.8%; diabetes duration, 16.4 ± 11.9 years; duration of CGM use, 2.1 ± 1.0 years; and mean HbA1c, 7.6 ± 0.9%). The average scan frequency was 10.5 ± 3.3 scan/day. Scan frequency was positively correlated with TIR and negatively correlated with TAR, although it was not significantly correlated with TBR. Scan frequency was positively correlated with the hypoglycemia fear survey-behavior score, while it was negatively correlated with some glycemic variability metrics. Adult patients with T1D and good exercise habits had a higher scan frequency than those without exercise habits. The AUC for > 70% of the TIR was 0.653, with an optimal cutoff of 11 scan/day. Conclusions: In real-world conditions, frequent scans were linked to improved CGM metrics, including increased TIR, reduced TAR, and some glycemic variability metrics. Exercise habits and hypoglycemia fear-related behavior might affect scan frequency. Our findings could help healthcare professionals use isCGM to support adults with T1D.Clinical Trial Registry No. UMIN000039376.

16.
Front Pharmacol ; 15: 1358573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601470

RESUMO

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: -3.5 ± 9.4 mL/min/1.73 m2/year, post: -0.4 ± 6.3 mL/min/1.73 m2/year, p < 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: -2.0 ± 10.9 mL/min/1.73 m2/year, post: -1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits-especially annual eGFR decline-of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.

17.
Methods Mol Biol ; 2604: 159-171, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36773232

RESUMO

Protonemata of the moss Physcomitrium patens are ideal structures in which to observe cytoskeletal organization and dynamics. Special care is needed to prepare P. patens cultures for high-resolution microscopy. Here, we describe methods for spinning disk microscopy of dividing P. patens cells expressing sGFP-tubulin and H2B-mCherry, including detailed methods for culturing P. patens.


Assuntos
Bryopsida , Microscopia , Citocinese , Tubulina (Proteína)
18.
Plant Methods ; 19(1): 100, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752568

RESUMO

BACKGROUND: Land plants exhibit a haplodiplontic life cycle, whereby multicellular bodies develop in both the haploid and diploid generations. The early-diverging land plants, known as bryophytes, have a haploid-dominant life cycle, in which a short-lived multicellular body in the diploid generation, known as the sporophyte, develops on the maternal haploid gametophyte tissues. The moss Physcomitrium (Physcomitrella) patens has become one of the most powerful model systems in evolutionary plant developmental studies. To induce diploid sporophytes of P. patens, several protocols are implemented. One of the conventional approaches is to grow approximately one-month-old gametophores for another month on Jiffy-7 pellets made from the peat moss that is difficult to fully sterilize. A more efficient method to obtain all tissues throughout the life cycle should accelerate studies of P. patens. RESULTS: Here, we investigated the effect of nitrogen conditions on the growth and development of P. patens. We provide an improved protocol for the sporophyte induction of P. patens using a BCD-based solid culture medium without Jiffy-7 pellets, based on the finding that the formation of gametangia and subsequent sporophytes is promoted by nitrogen-free growth conditions. The protocol consists of two steps; first, culture the protonemata and gametophores on nitrogen-rich medium under continuous light at 25 °C, and then transfer the gametophores onto nitrogen-free medium under short-day and at 15 °C for sporophyte induction. The protocol enables to shorten the induction period and reduce the culture space. CONCLUSIONS: Our more efficient and shortened protocol for inducing the formation of sporophytes will contribute to future studies into the fertilization or the diploid sporophyte generation of P. patens.

19.
Diabetol Int ; 14(2): 206-210, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36575722

RESUMO

We report a case of 77-year-old woman with fulminant type 1 diabetes (T1D) who developed diabetic ketoacidosis (DKA) after the second dose of SARS-CoV-2 vaccine tozinameran. The patient had been diagnosed as having T1D associated with an immune-related adverse event caused by pembrolizumab at the age of 75. After the second dose of tozinameran, she developed DKA and needed intravenous insulin infusion and mechanical ventilation. Although the direct causal relationship between the vaccination and the DKA episode could not be proven in this case, published literatures had suggested the possibility of developing DKA after SARS-CoV-2 vaccination in patients with T1D. As the magnitude of the risk of the combination of the known adverse drug reactions of SARS-CoV-2 mRNA vaccine and T1D patients' vulnerability to sick-day conditions is not yet thoroughly assessed, future studies such as a non-interventional study with adequate sample size would be required to address this issue.

20.
Life Sci Alliance ; 6(5)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36849250

RESUMO

Cell division is essential for development and involves spindle assembly, chromosome separation, and cytokinesis. In plants, the genetic tools for controlling the events in cell division at the desired time are limited and ineffective owing to high redundancy and lethality. Therefore, we screened cell division-affecting compounds in Arabidopsis thaliana zygotes, whose cell division is traceable without time-lapse observations. We then determined the target events of the identified compounds using live-cell imaging of tobacco BY-2 cells. Subsequently, we isolated two compounds, PD-180970 and PP2, neither of which caused lethal damage. PD-180970 disrupted microtubule (MT) organization and, thus, nuclear separation, and PP2 blocked phragmoplast formation and impaired cytokinesis. Phosphoproteomic analysis showed that these compounds reduced the phosphorylation of diverse proteins, including MT-associated proteins (MAP70) and class II Kinesin-12. Moreover, these compounds were effective in multiple plant species, such as cucumber (Cucumis sativus) and moss (Physcomitrium patens). These properties make PD-180970 and PP2 useful tools for transiently controlling plant cell division at key manipulation nodes conserved across diverse plant species.


Assuntos
Arabidopsis , Citocinese , Divisão Celular , Proteínas Associadas aos Microtúbulos/genética , Segregação de Cromossomos , Microtúbulos
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