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Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.
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Bases de Datos Factuales , Farmacovigilancia , Humanos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Vacunas contra la COVID-19/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , COVID-19/prevención & control , COVID-19/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Vacunas/efectos adversos , Organización Mundial de la Salud , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , Incidencia , Salud GlobalRESUMEN
The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
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Bases de Datos Factuales , Parálisis Facial , Farmacovigilancia , Organización Mundial de la Salud , Humanos , Parálisis Facial/epidemiología , Parálisis Facial/etiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Preescolar , Anciano , Incidencia , Vacunas/efectos adversos , Salud Global , COVID-19/prevención & control , COVID-19/epidemiología , Lactante , Vacunación/efectos adversos , Vacunación/estadística & datos numéricos , SARS-CoV-2/inmunologíaRESUMEN
INTRODUCTION: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). METHODS: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. RESULTS: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. CONCLUSION: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs.
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OBJECTIVE: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. METHODS: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. RESULTS: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). CONCLUSION: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.
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AIM: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data. MATERIALS AND METHODS: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC025 regarding the association between GLP-1RA use and suicidality. RESULTS: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC025 0.01]). CONCLUSIONS: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population.
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AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.
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Contaminación por Humo de Tabaco , Humanos , Contaminación por Humo de Tabaco/estadística & datos numéricos , Contaminación por Humo de Tabaco/efectos adversos , Adolescente , Salud Global , Femenino , Masculino , Fumar/epidemiología , Conducta del Adolescente , Prevalencia , Países en DesarrolloRESUMEN
Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.
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Leonurus , Enfermedades Respiratorias , Ratones , Animales , Leonurus/metabolismo , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Emisiones de Vehículos , Material Particulado , InflamaciónRESUMEN
Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 [95% CI, 13.58-27.56]), Serum ferritin (DOR, 24.90 [11.67-53.12]), N terminal proBNP (DOR, 21.03 [9.03-49.00]), and micro RNAs (DOR, 45.28 [6.30-325.52]), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 [95% CI, 2.37-25.09]), non-coding RNAs (DOR, 14.63 [3.24-66.14]), neutrophil to lymphocyte ratio (DOR, 6.62 [4.05-10.81]), platelet to lymphocyte ratio (DOR, 3.30 [2.10-5.19]), and C reactive protein (DOR, 6.58 [3.69-11.74]). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.
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BACKGROUND AND AIMS: Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. RESULTS: Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). CONCLUSIONS: The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.
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Esofagitis Eosinofílica , Masculino , Humanos , Esofagitis Eosinofílica/diagnóstico , Prevalencia , Incidencia , Europa (Continente) , América del NorteRESUMEN
Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.
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Quasi-bound state in the continuum (BIC) has significant potential because it supports an ultra-high quality factor (Q-factor). Here, we propose a graphene-embedded subwavelength grating that supports quasi-BIC for tuning very sharp Fano resonance transmission. The strongly enhanced light-graphene interaction from the quasi-BIC enables fine variation of the transmission at the resonant wavelength. The Q-factor of quasi-BIC significantly decreases as the Fermi level of graphene increases. We also propose a low-energy consumption THz-wave modulator using this scheme. The designed modulator shows approximately 100% modulation depth with a Fermi level shift of only EF = 90 meV.
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Many modern user interfaces are based on touch, and such sensors are widely used in displays, Internet of Things (IoT) projects, and robotics. From lamps to touchscreens of smartphones, these user interfaces can be found in an array of applications. However, traditional touch sensors are bulky, complicated, inflexible, and difficult-to-wear devices made of stiff materials. The touch screen is gaining further importance with the trend of current IoT technology flexibly and comfortably used on the skin or clothing to affect different aspects of human life. This review presents an updated overview of the recent advances in this area. Exciting advances in various aspects of touch sensing are discussed, with particular focus on materials, manufacturing, enhancements, and applications of flexible wearable sensors. This review further elaborates on the theoretical principles of various types of touch sensors, including resistive, piezoelectric, and capacitive sensors. The traditional and novel hybrid materials and manufacturing technologies of flexible sensors are considered. This review highlights the multidisciplinary applications of flexible touch sensors, such as e-textiles, e-skins, e-control, and e-healthcare. Finally, the obstacles and prospects for future research that are critical to the broader development and adoption of the technology are surveyed.
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Robótica , Dispositivos Electrónicos Vestibles , HumanosRESUMEN
We propose a new type of a mid-infrared ultra-compact optical modulator composed of a graphene metasurface. Unlike the previously proposed schemes based on loss variation of materials or interference, the proposed one utilizes the unique topological characteristic of the isofrequency contour in the hyperbolic metasurface to modulate the transmission. The designed modulator provides a modulation depth of 10.7 dB, the length of which is 750 nm, corresponding to â¼1/30 of an operating wavelength.
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KEY MESSAGE: IbSPF1, a novel target of IbMPK3/IbMPK6, regulates biotic stress response in sweetpotato. Environmental stresses due to biotic and abiotic factors negatively affect crop quality and productivity. To minimize the damage caused by these factors, numerous stress signaling pathways are activated in plants. Among these, the mitogen-activated protein kinase (MAPK) signaling cascade plays a pivotal role in diverse plant stress responses. MPK3 and MPK6 function in several cellular signaling pathways by phosphorylating downstream partner proteins in response to environmental stresses. However, little is known about the MPK3/MPK6 signaling pathway in sweetpotato [Ipomoea batatas (L.) Lam]. We recently confirmed that IbMPK3 and IbMPK6, two pathogen-responsive MAPKs, play essential roles in defense gene activation in sweetpotato. In this study, we show that sweetpotato SP8-binding factor (IbSPF1), a substrate of IbMPK3/IbMPK6, functions as a transcriptional regulator of biotic stress signaling in sweetpotato. IbSPF1 specifically interacts with IbMPK3 and IbMPK6, which phosphorylate Ser75 and Ser110 residues of IbSPF1. This increases the affinity of IbSPF1 for the W-box element in target gene promoters. Additionally, the expression of IbSPF1 was up-regulated under various stress conditions and different hormone treatments involved in plant defense responses. Interestingly, the phospho-mimicking mutant of IbSPF1 showed enhanced resistance to Pseudomonas syringae pv. tabaci, and transient expression of mutant IbSPF1 induced the expression of pathogenesis-related genes. These results indicate that the phosphorylation of IbSPF1 by IbMPK3/IbMPK6 plays a critical role in plant immunity by up-regulating the expression of downstream genes.
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Proteínas de Unión al ADN/metabolismo , Ipomoea batatas/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Ipomoea batatas/enzimología , Fosforilación , Inmunidad de la Planta , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiones Promotoras Genéticas , Pseudomonas syringae , Transducción de Señal , Estrés Fisiológico/genética , Nicotiana/genética , Nicotiana/metabolismo , Factores de Transcripción/genéticaRESUMEN
KEY MESSAGE: IbOr-R96H resulted in carotenoid overaccumulation and enhanced abiotic stress tolerance in transgenic sweetpotato calli. The Orange (Or) protein is involved in the regulation of carotenoid accumulation and tolerance to various environmental stresses. Sweetpotato IbOr, with strong holdase chaperone activity, protects a key enzyme, phytoene synthase (PSY), in the carotenoid biosynthetic pathway and stabilizes a photosynthetic component, oxygen-evolving enhancer protein 2-1 (PsbP), under heat and oxidative stresses in plants. Previous studies of various plant species demonstrated that a single-nucleotide polymorphism (SNP) from Arg to His in Or protein promote a high level of carotenoid accumulation. Here, we showed that the substitution of a single amino acid at position 96 (Arg to His) of wild-type IbOr (referred to as IbOr-R96H) dramatically increases carotenoid accumulation. Sweetpotato calli overexpressing IbOr-WT or IbOr-Ins exhibited 1.8- or 4.3-fold higher carotenoid contents than those of the white-fleshed sweetpotato Yulmi (Ym) calli, and IbOr-R96H overexpression substantially increased carotenoid accumulation by up to 23-fold in sweetpotato calli. In particular, IbOr-R96H transgenic calli contained 88.4-fold higher levels of ß-carotene than those in Ym calli. Expression levels of carotenogenesis-related genes were significantly increased in IbOr-R96H transgenic calli. Interestingly, transgenic calli overexpressing IbOr-R96H showed increased tolerance to salt and heat stresses, with similar levels of malondialdehyde to those in calli expressing IbOr-WT or IbOr-Ins. These results suggested that IbOr-R96H is a useful target for the generation of efficient industrial plants, including sweetpotato, to cope with growing food demand and climate change by enabling sustainable agriculture on marginal lands.
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Sustitución de Aminoácidos/genética , Carotenoides/metabolismo , Ipomoea batatas/genética , Chaperonas Moleculares/genética , Proteínas de Plantas/genética , Respuesta al Choque Térmico , Ipomoea batatas/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Tolerancia a la Sal , Estrés Fisiológico , beta Caroteno/biosíntesis , beta Caroteno/genéticaRESUMEN
Lignans are known to be an important class of phenylpropanoid secondary metabolites. In the course of our studies on the chemodiversity of lignans, the necessity arose to develop a method for the fast detection and identification of bioactive lignan subclasses. In this study, we detected 10 lignan derivatives of different extracts of F. viridissima by UHPLC-ESI-QTOF-MS. Lignan glycosides (1 and 2), lignans (3 and 4), and lignan dimers (5-10) were identified by analysis of their exact masses and MSe spectra along with the characteristic mass fragmentation patterns and molecular formulas. We further investigated NO inhibitory effects of F. viridissima fractions and their major lignan derivatives to evaluate those anti-inflammatory effects. The methylene chloride fraction of F. viridissima as well as compounds 8 and 10 showed potent dose-dependent NO inhibitory effects on RAW 264.7 cells. Corresponding to the NO inhibition by compounds 8 and 10, lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression was notably reduced by both compounds. Our combined data with the bioactive results and the component analysis by UHPLC-ESI-QTOF-MS suggest that the methylene chloride fraction of F. viridissima roots could be potential anti-inflammatory agents and these are related to major lignans including dimeric dibenzylbutyrolactone lignans.
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Forsythia/química , Lignanos/química , Lignanos/farmacología , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Raíces de Plantas/química , Células RAW 264.7 , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Since the molecular self-assembly of nanomaterials is sensitive to their surface properties, the molecular packing structure on the surface is essential to build the desired chemical and physical properties of nanomaterials. Here, a new nanosurfactant is proposed for the automatic construction of macroscopic surface alignment layer for liquid crystal (LC) molecules. An asymmetric nanosurfactant (C60 NS) consisted of mesogenic cyanobiphenyl moieties with flexible alkyl chains and a [60]fullerene nanoatom is newly designed and precisely synthesized. The C60 NS directly introduced in the anisotropic LC medium is self-assembled into the monolayered protrusions on the surface because of its amphiphilic nature originated by asymmetrically programmed structural motif of LC-favoring moieties and LC-repelling groups. The monolayered protrusions constructed by the phase-separation and self-assembly of asymmetric C60 NS nanosurfactant in the anisotropic LC media amplify and transfer the molecular orientational order from surface to bulk, and finally create the automatic vertical molecular alignment on the macroscopic length scale. The asymmetric C60 NS nanosurfactant and its self-assembly described herein can offer the direct guideline of interface engineering for the automatic molecular alignments.
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We numerically demonstrate optical bistability in a nonlinear multilayer structure by utilizing the unique dispersion of hyperbolic metamaterials. The linear transmission is varied sharply with topological transition of isofrequency contour of the multilayer structure, and this non-resonant scheme enables realization of optical bistability with a short response time and a relatively low switching intensity. We have investigated exhaustively all possible topological transitions in the dispersion characteristics of the multilayer structure for optical bistability, and shown that the hyperbolic metamaterial (HMM) type transition from Type II to Type I, and the transition from Type II HMM to effective dielectric are suitable for realizing high-performances optical bistability. The proposed schemes can overcome the trade-off between a switching intensity and a response time in resonance based optical bistabilities.