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1.
J Org Chem ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669291

RESUMEN

The regioselective modification of polyols allows rapid access to their derivatives, thereby accelerating the polyol-related biology and drug discovery. We previously reported that benzoxaborole is a potent catalyst for the regioselective modification of polyols containing a cis-1,2-diol structure. In this study, we developed a bifunctional benzoxaborole catalyst embedded with a Lewis base. Benzoxaborole and Lewis base groups were designed to cooperatively activate a substrate (cis-1,2-diol) and reactant (electrophile), respectively, hence lowering the reaction barrier for the cis-1,2-diol moiety. The bifunctional catalyst indeed exhibited a significantly higher catalytic activity and selectivity for cis-1,2-diol modifications rather than a benzoxaborole catalyst without a Lewis base group. Mechanistic analyses, using both experimental and theoretical methods, supported the design of our catalyst. The bifunctional catalyst reported herein would be a new tool for the straightforward synthesis of polyol derivatives.

2.
BMC Med Inform Decis Mak ; 24(1): 47, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38350972

RESUMEN

This paper introduces a forensic psychiatry database established in Japan and discusses its significance and future issues. The purpose of this Database, created under the Medical Treatment and Supervision Act (MTSA) Database Project, is to improve the quality of forensic psychiatry treatment. It can collect monthly data on "basic information," "Orders and hospitalizations under the MTSA," "Treatment process," "Criminal and medical treatment history," and "problematic behavior in the unit." The online system has accumulated data on more than 8,000 items in 24 broad categories. Medical data are exported from the medical care assisting system of 32 designated inpatient facilities in XML format and then saved on USB memory sticks. The files are imported into the Database system client, which sends the data to the Database server via a virtual private network. This system minimizes errors and efficiently imports patient data. However, there is a limitation that it is difficult to set items that need to be analyzed to solve everyday clinical problems into the database system because they tend to change over time. By evaluating the effectiveness of the Database, and collecting appropriate data, it is expected to disseminate a wide range of knowledge that will contribute to the future development of mental health and welfare care.


Asunto(s)
Servicios de Salud Mental , Humanos , Psiquiatría Forense , Hospitalización , Japón , Sistemas en Línea
3.
Cancer Sci ; 115(5): 1634-1645, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38411285

RESUMEN

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.


Asunto(s)
Biomarcadores de Tumor , Ácido Homovanílico , Neuroblastoma , Ácido Vanilmandélico , Humanos , Neuroblastoma/orina , Neuroblastoma/diagnóstico , Masculino , Femenino , Medición de Riesgo , Preescolar , Biomarcadores de Tumor/orina , Lactante , Ácido Homovanílico/orina , Ácido Vanilmandélico/orina , Niño , Catecolaminas/orina , Estudios de Casos y Controles , Dopamina/orina , Dopamina/análogos & derivados , Cromatografía Liquida
4.
Front Psychiatry ; 14: 1243859, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860168

RESUMEN

Backgrounds: Patients with schizophrenia suffer from cognitive impairment that worsens real-world functional outcomes. We previously reported that multi-session transcranial direct current stimulation (tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) improved daily living skills, while stimulation on the left superior temporal sulcus (STS) enhanced performance on a test of social cognition in these patients. To examine the region-dependent influence of tDCS on daily-living skills, neurocognition, and psychotic symptoms, this study compared effects of anodal stimulation targeting either of these two brain areas in patients with schizophrenia. Methods: Data were collected from open-label, single-arm trials with anodal electrodes placed over the left DLPFC (N = 28) or STS (N = 15). Daily-living skills, neurocognition, and psychotic symptoms were measured with the UCSD performance-based skills assessment-brief (UPSA-B), Brief Assessment of Cognition in Schizophrenia (BACS), and Positive and Negative Syndrome Scale (PANSS), respectively. After baseline evaluation, tDCS (2 mA × 20 min) were delivered two times per day for 5 consecutive days. One month after the final stimulation, clinical assessments were repeated. Results: Performance on the UPSA-B was significantly improved in patients who received anodal tDCS at the left DLPFC (d = 0.70, p < 0.001), while this effect was absent in patients with anodal electrodes placed on the left STS (d = 0.02, p = 0.939). Significant improvement was also observed for scores on the BACS with anodal tDCS delivered to the DLPFC (d = 0.49, p < 0.001); however, such neurocognitive enhancement was absent when the STS was stimulated (d = 0.05, p = 0.646). Both methods of anodal stimulation showed a significant improvement of General Psychopathology scores on the PANSS (DLPFC, d = 0.50, p = 0.027; STS, d = 0.44, p = 0.001). Conclusion: These results indicate the importance of selecting brain regions as a target for tDCS according to clinical features of individual patients. Anodal stimulation of the left DLPFC may be advantageous in improving higher level functional outcomes in patients with schizophrenia. Trial registration: These studies were registered within the University hospital Medical Information Network Clinical Trials Registry [(24), UMIN000015953], and the Japan Registry of Clinical Trials [(28), jRCTs032180026].

5.
ACS Appl Mater Interfaces ; 15(23): 27560-27567, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37276244

RESUMEN

Peptide sequence periodicity is a simple design tool that can be used to generate functional peptide-based surface coatings. De novo-designed peptide N3-PEG-VK16 is characterized by a hydrophobic periodicity of two that avidly binds to native polystyrene priming its surface for subsequent targeted functionalization via chemical ligation. The peptidic portion of N3-PEG-VK16 is responsible for surface binding, converting polystyrene's hydrophobic surface into a wettable and electrostatically charged environment that facilitates cell attachment. Native polystyrene surfaces are coated by simple peptide adsorption from an aqueous buffered solution, and the resulting primed surface is easily functionalized by cycloaddition chemistry. Herein, we show that ligating a vitronectin-derived peptide to primed polystyrene surfaces enables adhesion, expansion, long-term culture, and phenotype maintenance of human induced pluripotent stem cells. To demonstrate scope, we also show that additional functional ligands can be used, for example, nerve growth factor protein, to control neurite outgrowth.


Asunto(s)
Células Madre Pluripotentes Inducidas , Poliestirenos , Humanos , Poliestirenos/química , Adhesión Celular , Péptidos/farmacología , Vitronectina/química , Propiedades de Superficie
6.
J Phys Chem A ; 127(23): 4940-4948, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37262017

RESUMEN

Conformer-selected electronic and vibrational spectra of benzyl methyl ether and its terminal methyl group-substituted derivative in a supersonic jet have been measured using ultraviolet (UV)-UV hole burning and fluorescence-detected infrared spectroscopy to investigate the conformational stability of flexible molecules. Various quantum chemical calculations as well as experimental observations reveal the coexistence of three conformers with different CCOC dihedral angles and side-chain orientations relative to the benzene ring plane. Vibrational analysis in the excited state with time-dependent density functional theory and IR simulations containing anharmonic coupling sufficiently reproduce the experimental results, suggesting that these three conformers can be distinguished into one gauche-conformer and two trans-ones with respect to the CCOC dihedral angle. We also observe that the gauche conformer exhibits higher-frequency CH2 modes. The natural bond orbital analysis indicates that this phenomenon is attributed to the electron delocalization from the non-bonding orbitals and the C-O orbitals associated with the neighboring oxygen atom, which leads to a conformer dependence of the methylene C-H bond strength.

7.
Sci Rep ; 13(1): 10430, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37369727

RESUMEN

Laminins are a family of heterotrimers composed of α-, ß-, and γ-chains in the basement membrane. Five α chains contain laminin globular (LG) domain consisting of five tandem modules (LG1-5 modules) at their C-terminus. Each LG45 modules is connected to a compact cloverleaf-shaped structure of LG1-3 through a flexible linker. Although the accumulated studies of the LG45 modules have suggested differences in each α chain regarding the binding of carbohydrate chain and intramolecular interaction, this remains unclear. In this study, to characterize their functions comparatively, we produced recombinant proteins of LG45 modules of human laminin α1-5 chains. Dystroglycan (DG) modified with matriglycan readily bound to the LG45 modules of α1 and α2 chains but not to the other α chains. In contrast, heparin bound to the LG45 modules of the α chains, except for α2. The binding of heparan sulfate/heparin-linked syndecans (SDCs) to LG45 modules was influenced by their core proteins. Furthermore, the α1 and α4LG45 modules bound to SDCs in a pH-dependent manner. A cell adhesion assay showed that HEK293 cells could readily adhere to the LG45 modules of α3-5 chains through a combination of SDCs and integrins. Moreover, α5LG45 modules bound to the E8 fragment, which includes the C-terminus of the laminin coiled-coil (LCC) domain and LG1-3 modules, but α2LG45 modules did not. The results suggested that although α5LG45 modules was fixed within the LG domain, α2LG45 modules was freely placed in the vicinity of LG1-3. Our findings provide information for investigation of the structural and functional diversity of basement membranes.


Asunto(s)
Heparitina Sulfato , Laminina , Humanos , Laminina/metabolismo , Células HEK293 , Unión Proteica/fisiología , Heparina/metabolismo , Sitios de Unión
8.
BMJ Glob Health ; 8(5)2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37247873

RESUMEN

INTRODUCTION: We investigated the effect of social media-based interventions on COVID-19 vaccine intention (VI) and confidence in Japan. METHODS: We conducted a three-arm randomised controlled trial between 5 November 2021 and 9 January 2022 during a low incidence (<1000/day) of COVID-19 in Japan in the midst of the second and the third waves. Japanese citizens aged ≥20 who had not received any COVID-19 vaccine and did not intend to be vaccinated were randomly assigned to one of the following three groups: (1) a control group, (2) a group using a mobile app chatbot providing information on COVID-19 vaccines and (3) a group using interactive webinars with health professionals. VI and predefined Vaccine Confidence Index (VCI) measuring confidence in the importance, safety and effectiveness were compared before and after the interventions under intention-to-treat principle. Logistic regression models were used to investigate the effect of each intervention on postintervention VI and changes of VCI compared with control. RESULTS: Among 386 participants in each group, 359 (93.0%), 231 (59.8%) and 207 (53.6%) completed the postsurvey for the control, chatbot and webinar groups, respectively. The average duration between the intervention and the postsurvey was 32 days in chatbot group and 27 days in webinar group. VI increased from 0% to 18.5% (95% CI 14.5%, 22.5%) in control group, 15.4% (95% CI 10.8%, 20.1%) in chatbot group and 19.7% (95% CI 14.5%, 24.9%) in webinar group without significant difference (OR for improvement=0.8 (95% CI 0.5, 1.3), p=0.33 between chatbot and control, OR=1.1 (95% CI 0.7, 1.6), p=0.73 between webinar and control). VCI change tended to be larger in chatbot group compared with control group without significant difference (3.3% vs -2.5% in importance, OR for improvement=1.3 (95% CI 0.9, 2.0), p=0.18; 2.5% vs 1.9% in safety, OR=1.1 (95% CI 0.7, 1.9), p=0.62; -2.4% vs -7.6% in effectiveness, OR=1.4 (95% CI 0.9, 2.1), p=0.09). Improvement in VCI was larger in webinar group compared with control group for importance (7.8% vs -2.5%, OR=1.8 (95% CI 1.2, 2.8), p<0.01), effectiveness (6.4% vs -7.6%, OR=2.2 (95% CI 1.4, 3.4), p<0.01) and safety (6.0% vs 1.9%, OR=1.6 (95% CI 1.0, 2.6), p=0.08). CONCLUSION: This study demonstrated that neither the chatbot nor the webinar changed VI importantly compared with control. Interactive webinars could be an effective tool to change vaccine confidence. Further study is needed to identify risk factors associated with decreased vaccine confidence and investigate what intervention can increase VI and vaccine confidence for COVID-19 vaccines. TRIAL REGISTRATION NUMBER: UMIN000045747.


Asunto(s)
COVID-19 , Aplicaciones Móviles , Vacunas , Humanos , Vacunas contra la COVID-19 , COVID-19/prevención & control , Intención , Japón
10.
Int J Hematol ; 117(6): 910-918, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36867356

RESUMEN

Minimal residual disease (MRD) is usually defined as the small number of cancer cells that remain in the body after treatment. The clinical significance of MRD kinetics is well recognized in treatment of hematologic malignancies, particularly acute lymphoblastic leukemia (ALL). Real time quantitative PCR targeting immunoglobulin (Ig) or T-cell receptor (TCR) rearrangement (PCR-MRD), as well as multiparametric flow cytometric analysis targeting antigen expression, are widely used in MRD detection. In this study, we devised an alternative method to detect MRD using droplet digital PCR (ddPCR), targeting somatic single nucleotide variants (SNVs). This ddPCR-based method (ddPCR-MRD) had sensitivity up to 1E-4. We assessed ddPCR-MRD at 26 time points from eight T-ALL patients, and compared it to the results of PCR-MRD. Almost all results were concordant between the two methods, but ddPCR-MRD detected micro-residual disease that was missed by PCR-MRD in one patient. We also measured MRD in stored ovarian tissue of four pediatric cancer patients, and detected 1E-2 of submicroscopic infiltration. Considering the universality of ddPCR-MRD, the methods can be used as a complement for not only ALL, but also other malignant diseases regardless of tumor-specific Ig/TCR or surface antigen patterns.


Asunto(s)
Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasia Residual/patología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Mutación , Receptores de Antígenos de Linfocitos T/genética
11.
J Phys Chem A ; 127(11): 2536-2544, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36919254

RESUMEN

The structures of hydrogen-bonded benzoxazole clusters with methanol and ammonia, BO-(CH3OH)n (n = 1-3) and BO-(NH3)n (n = 1, 2), in a supersonic jet have been investigated by measuring the S1-S0 electronic spectra and isomer-selected vibrational spectra with the aid of quantum chemical calculations. Similar to BO-(H2O)1, two isomers of BO-(NH3)1 were observed, which form two types of hydrogen bond networks starting from the CH bond at the 2-/7-position to the nitrogen atom of BO (C2HN/C7HN). The relative stability of these isomers strongly depends on solvent molecules. Natural bond orbital analysis reveals that the OH···N hydrogen bond is dominant in BO-(H2O)1 and that intermolecular interaction between the CH group and the nitrogen atom of ammonia, especially C2H···N, is significantly enhanced, resulting in a more stable C2HN isomer. Symmetry-adapted perturbation theory calculations indicate that the dispersion interaction between the methyl group of methanol and π electron cloud on the BO ring is responsible for the extreme stability of the C7HN of BO-(CH3OH)1. Furthermore, using time-dependent density functional theory calculations, the isomer tendency of the electronic transition shifts from the monomer origin is reproduced and it is proposed that the significant blue shift in C2HN is due to the shortened C2H bond length upon electronic excitation.

13.
ACS Omega ; 8(5): 4687-4693, 2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36777587

RESUMEN

The RGD motif is a cell adhesion sequence that binds to integrins, a receptor family for extracellular matrix proteins. We previously reported that the RGDX1X2 sequence, where X1X2 is VF or NY, is required for integrin αvß5-mediated cell adhesion. However, the importance and applications of the X1X2 combinations and their surrounding sequences of integrin αvß5-binding RGDX1X2-containing peptides have not been comprehensively elucidated. Therefore, we aimed to identify an RGD-containing peptide with enhanced integrin αvß5 binding activity. We synthesized various peptides based on the RGDVF and RGDNY peptides to optimize the N-terminal, C-terminal, and X1X2 combinations of the RGDX1X2 sequence. These peptides were immobilized on maleimide-functionalized bovine serum albumin-coated plates via a thiol-maleimide reaction, and cell adhesion was evaluated using HeLa cells and human dermal fibroblasts. Consequently, CPPP-RGDTF and CPPP-RGDTFI were identified as highly active peptides for integrin αvß5-mediated cell adhesion. CPPP-RGDTF and CPPP-RGDTFI are expected to serve as cell adhesion molecules for developing culture substrates and biomaterials. Furthermore, these findings provide important novel insights into the interaction between the RGD motifs and integrins.

14.
Dalton Trans ; 52(3): 572-582, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36537300

RESUMEN

Iron complexes bearing 1,2,3-triazol-5-ylidene were synthesized and applied to the reaction with hydrosilane and homogeneous catalytic hydrosilylation of aromatic ketones and aldehydes. Addition of a free carbene to a solution of Fe(CO)4Br2 yielded an octahedral, diamagnetic and cationic iron(II) complex [Fe(1,2,3-triazolylidene)(CO)2Br]+. Pyrolysis of the dicarbonyl complex eliminated the two CO ligands to form a paramagnetic four-coordinate complex. A theoretical study using DFT calculations indicated that the spin state changed from singlet to quintet during ligand elimination. Investigations of the successful hydrosilylation of acetophenone and benzaldehyde derivatives using MIC-iron(II) bromide suggested the importance of the base for efficient conversion in the catalytic process. The bromide-to-hydride exchange reaction, transmetallation, of MIC-iron(II) bromide in the presence of KOtBu and HSi(OEt)3 which could occur in the initial process of hydrosilylation was proposed, and supported by a theoretical study.

15.
Clin EEG Neurosci ; 54(6): 601-610, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34898301

RESUMEN

Backgrounds. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, eg, mood disorders and schizophrenia. Although tDCS provides a promising approach, its neurobiological mechanisms remain to be explored. Objectives. To provide a systematic review of animal studies, and consider how tDCS ameliorates psychiatric conditions. Methods. A literature search was conducted on English articles identified by PubMed. We defined the inclusion criteria as follows: (1) articles published from the original data; (2) experimental studies in animals; (3) studies delivering direct current transcranially, ie, positioning electrodes onto the skull. Results. 138 papers met the inclusion criteria. 62 papers deal with model animals without any dysfunctions, followed by 52 papers for neurological disorder models, and 12 for psychiatric disorder models. The most studied category of functional areas is neurocognition, followed by motor functions and pain. These studies overall suggest the role for the late long-term potentiation (LTP) via anodal stimulation in the therapeutic effects of tDCS. Conclusions. tDCS Anodal stimulation may provide a novel therapeutic strategy to particularly enhance neurocognition in psychiatric disorders. Its mechanisms are likely to involve facilitation of the late LTP.


Asunto(s)
Trastornos Mentales , Estimulación Transcraneal de Corriente Directa , Animales , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Electroencefalografía , Trastornos Mentales/terapia , Potenciación a Largo Plazo/fisiología , Encéfalo
16.
Gan To Kagaku Ryoho ; 50(13): 1724-1726, 2023 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-38303186

RESUMEN

A 76-year-old male patient underwent a distal gastrectomy for advanced gastric cancer. As the postoperative serum CA19-9 level was elevated, chemotherapy was initiated. Computed tomography(CT)detected a solitary peritoneal recurrence in the left subhepatic space 17 months later. Consequently, chemoradiotherapy(CRT)at a total dose of 60 Gy, combined with S-1 therapy, was administered for local tumor control. After CRT, CT scans revealed a remarkable reduction in the peritoneal recurrence. Presently, 8 months after CRT, the patient remains alive with no indications of regrowth. CRT could prove efficacious as a treatment for gastric cancer patients with localized peritoneal recurrences.


Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Masculino , Humanos , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Quimioradioterapia , Cavidad Peritoneal , Gastrectomía , Recurrencia Local de Neoplasia/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia
17.
JAMA Pediatr ; 2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-36190704

RESUMEN

Importance: The risk and benefits of COVID-19 vaccination during pregnancy are under investigation. Pooled evidence regarding neonatal and maternal outcomes in association with COVID-19 vaccination during pregnancy is scarce. Objective: To evaluate the association between COVID-19 vaccination during pregnancy and peripartum outcomes. Data Sources: PubMed and EMBASE databases were searched on April 5, 2022. Language restrictions were not applied. Study Selection: Prospective trials and observational studies comparing the individuals who received at least 1 COVID-19 vaccination during pregnancy with those who did not and reporting the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, neonatal intensive care units (NICU) admission, and intrauterine fetal death (IFD). Data Extraction and Synthesis: Two independent investigators extracted relevant data from each study. Odds ratios (ORs) were calculated using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Main Outcomes and Measures: The primary outcomes were the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, NICU admission, and IFD. The secondary outcomes were maternal outcomes, including maternal SARS-CoV-2 infection, cesarean delivery, postpartum hemorrhage, and chorioamnionitis. Results: Nine observational studies involving 81 349 vaccinated (mean age, 32-35 years) and 255 346 unvaccinated individuals during pregnancy (mean age, 29.5-33 years) were included. COVID-19 vaccination during pregnancy was associated with lower risk of NICU admission (OR, 0.88; 95% CI, 0.80-0.97) and IFD (OR, 0.73; 95% CI, 0.57-0.94), whereas there was no statistically significant association with preterm birth (OR, 0.89; 95% CI, 0.76-1.04), small for gestational age (OR, 0.99; 95% CI, 0.94-1.04), and low Apgar score (OR, 0.94; 95% CI, 0.87-1.02). COVID-19 vaccination during pregnancy was associated with a lower risk of maternal SARS-CoV-2 infection (OR, 0.46; 95% CI, 0.22-0.93), whereas it was not associated with increased risk of cesarean delivery (OR, 1.05; 95% CI, 0.93-1.20), postpartum hemorrhage (OR, 0.95; 95% CI, 0.83-1.07), and chorioamnionitis (OR, 0.95; 95% CI, 0.83-1.07). Conclusions and Relevance: COVID-19 vaccination during pregnancy was not associated with an increase in the risk of peripartum outcomes, was associated with a decreased risk of NICU admission, IFD, and maternal SARS-CoV-2 infection. Thus, COVID-19 vaccination should be encouraged for pregnant individuals.

18.
Molecules ; 27(19)2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36235147

RESUMEN

The hA5G18 peptide (DDFVFYVGGYPS) identified from the human laminin α5 chain G domain promotes cell attachment and spreading when directly coated on a plastic plate, but does not show activity when it is conjugated on a chitosan matrix. Here, we focused on the structural requirement of hA5G18 for activity. hA5G18 was stained with Congo red and formed amyloid-like fibrils. A deletion analysis of hA5G18 revealed that FVFYV was a minimum active sequence for the formation of amyloid-like fibrils, but FVFYV did not promote cell attachment. Next, we designed functional fibrils using FVFYV as a template for amyloid-like fibrils. When we conjugated an integrin binding sequence Arg-Gly-Asp (RGD) to the FVFYV peptide with Gly-Gly (GG) as a spacer, FVFYVGGRGD promoted cell attachment in a plate coat assay, but a negative control sequence RGE conjugated peptide, FVFYVGGRGE, also showed activity. However, when the peptides were conjugated to Sepharose beads, the FVFYVGGRGD beads showed cell attachment activity, but the FVFYVGGRGE beads did not. These results suggest that RGD and RGE similarly contribute to cell attachment activity in amyloid-like fibrils, but only RGD contributes the activity on the Sepharose beads. Further, we conjugated a basic amino acid (Arg, Lys, and His) to the FVFYV peptide. Arg or Lys-conjugated FVFYV peptides, FVFYVGGR and FVFYVGGK, showed cell attachment activity when they were coated on a plate, but a His-conjugated FVFYV peptide FVFYVGGH did not show activity. None of the basic amino acid-conjugated peptides showed cell attachment in a Sepharose bead assay. The cell attachment and spreading on FVFYVGGR and FVFYVGGK were inhibited by an anti-integrin ß1 antibody. These results suggest that the Arg and Lys residues play critical roles in the interaction with integrins in amyloid-like fibrils. FVFYV is useful to use as a template for amyloid-like fibrils and to develop multi-functional biomaterials.


Asunto(s)
Quitosano , Rojo Congo , Secuencia de Aminoácidos , Aminoácidos Básicos , Amiloide/metabolismo , Materiales Biocompatibles , Adhesión Celular/fisiología , Humanos , Laminina , Oligopéptidos , Péptidos/farmacología , Plásticos , Sefarosa
19.
Biol Pharm Bull ; 45(10): 1537-1543, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36184513

RESUMEN

Octa-arginine (R8) is a cell-permeable peptide with excellent cell adhesion properties. Surface-immobilized R8 mediates cell attachment via cell surface receptors, such as heparan sulfate proteoglycans and integrin ß1, and promotes cell spreading and proliferation. However, it is not clear how these properties are affected by specific peptide composition and if they could be improved. Here, we synthesized XR8 peptides, in which half of the original R8 arginine residues were replaced with another amino acid (X). We then aimed to investigate the effect of the substitution on cell adhesion and proliferation on XR8-conjugated agarose matrices. The XR8-matrix showed slightly better cell attachment when X was a hydrophobic or aromatic amino acid. However, hydrophobic XR8-matrices tended to promote cell proliferation to a less extent. Eventually, YR8-matrix most efficiently promoted cell adhesion, spreading, and proliferation among the XR8-matrices tested. Collectively, these observations indicate that the properties of residue X play a major role in the biological activity of XR8-matrices and shed light on the interaction between small peptides and the cell membrane. Further, YR8 is a promising cell-adhesive peptide for the development of cell culture substrates and biomaterials.


Asunto(s)
Proteoglicanos de Heparán Sulfato , Integrina beta1 , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Aminoácidos Aromáticos/farmacología , Arginina/farmacología , Materiales Biocompatibles/farmacología , Adhesión Celular , Proteoglicanos de Heparán Sulfato/farmacología , Integrina beta1/farmacología , Péptidos/metabolismo , Péptidos/farmacología , Sefarosa
20.
Matrix Biol Plus ; 15: 100118, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35990309

RESUMEN

The linkage between the basement membrane (BM) and cytoskeleton is crucial for muscle fiber stability and signal transduction. Mutations in the linkage molecules can cause various types of muscular dystrophies. The different severities and times of onset suggest that compensatory linkages occur at the sarcolemma. Cluster of differentiation 239 (CD239) binds to the α5 subunit of laminin-511 extracellularly and is connected to spectrin intracellularly, resulting in a linkage between the BM and cytoskeleton. In this study, we explored the linkage of laminin α5_CD239_spectrin in skeletal muscles. Although laminin α5, CD239, and spectrin were present in embryonic skeletal muscles, they disappeared in adult skeletal muscle tissues, except for the soleus and diaphragm. Laminin α5_CD239_spectrin was localized in the skeletal muscle tissues of Duchenne muscular dystrophy and congenital muscular dystrophy mouse models. The experimental regeneration of skeletal muscle increased the CD239-mediated linkage, indicating that it responds to regeneration, but not to genetic influence. Furthermore, in silico analysis showed that laminin α5_CD239_spectrin was upregulated by steroid therapy for muscular dystrophy. Therefore, CD239-mediated linkage may serve as a therapeutic target to prevent the progression of muscular dystrophy.

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