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1.
Nat Commun ; 15(1): 5875, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997266

ABSTRACT

Correct regulation of intercellular communication is a fundamental requirement for cell differentiation. In Arabidopsis thaliana, the female germline differentiates from a single somatic ovule cell that becomes encased in ß-1,3-glucan, a water insoluble polysaccharide implicated in limiting pathogen invasion, regulating intercellular trafficking in roots, and promoting pollen development. Whether ß-1,3-glucan facilitates germline isolation and development has remained contentious, since limited evidence is available to support a functional role. Here, transcriptional profiling of adjoining germline and somatic cells revealed differences in gene expression related to ß-1,3-glucan metabolism and signalling through intercellular channels (plasmodesmata). Dominant expression of a ß-1,3-glucanase in the female germline transiently perturbed ß-1,3-glucan deposits, allowed intercellular movement of tracer molecules, and led to changes in germline gene expression and histone marks, eventually leading to termination of germline development. Our findings indicate that germline ß-1,3-glucan fulfils a functional role in the ovule by insulating the primary germline cell, and thereby determines the success of downstream female gametogenesis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Gametogenesis, Plant , Gene Expression Regulation, Plant , Ovule , beta-Glucans , Arabidopsis/metabolism , Arabidopsis/genetics , Ovule/metabolism , Ovule/genetics , beta-Glucans/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Gametogenesis, Plant/genetics , Plasmodesmata/metabolism , Pollen/metabolism , Pollen/genetics , Pollen/growth & development , Gene Expression Profiling
3.
Glob Health Action ; 17(1): 2362310, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38904186

ABSTRACT

Spiritual Intelligence (SI) is an independent concept from spirituality, a unifying and integrative intelligence that can be trained and developed, allowing people to make use of spirituality to enhance daily interaction and problem solving in a sort of spirituality into action. To comprehensively map and analyze current knowledge on SI and understand its impact on mental health and human interactions, we conducted a scoping review following the Joanna Briggs Institute methodology, searching for 'spiritual intelligence' across PubMedCentral, Scopus, WebOfScience, and PsycInfo. Quantitative studies using validated SI instruments and reproducible methodologies, published up to 1 January 2022, were included. Selected references were independently assessed by two reviewers, with any disagreements resolved by a third reviewer. Data were extracted using a data extraction tool previously developed and piloted. From this search, a total of 69 manuscripts from 67 studies were included. Most studies (n = 48) were conducted in educational (n = 29) and healthcare (n = 19) settings, with the Spiritual Intelligence Self Report Inventory (SISRI-24) emerging as the predominant instrument for assessing SI (n = 39). Analysis revealed several notable correlations with SI: resilience (n = 7), general, mental, and spiritual health (n = 6), emotional intelligence (n = 5), and favorable social behaviors and communication strategies (n = 5). Conversely, negative correlations were observed with burnout and stress (n = 5), as well as depression and anxiety (n = 5). These findings prompt a discussion regarding the integration of the SI concept into a revised definition of health by the World Health Organization and underscore the significance of SI training as a preventative health measure.


Main findings: This scoping review of Spiritual Intelligence found positive correlations with resilience, general, mental and spiritual health, emotional intelligence, and favourable social behaviours and communication strategies, and negative correlations with burnout, stress, depression, and anxiety.Added knowledge: Spiritual Intelligence is an all-inclusive way to approach spirituality from a practical, daily problem-solving perspective that can be trained with several benefits for personal overall health, while also fostering substantial personal growth in social behaviors and skills.Global health impact for policy and action: Spiritual Intelligence training is urgently needed and should be integrated into global educational programs from early childhood as a health promotion strategy aiming to foster a more resilient and compassionate society.


Subject(s)
Mental Health , Spirituality , Humans , Intelligence , Emotional Intelligence
4.
Int J Mol Sci ; 25(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38791419

ABSTRACT

Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (BRAF- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PI3KCA)-mutant), although MET did not affect either 3H-deoxy-D-glucose or 14C-butyrate uptake and lactate production, and ASP caused only a small decrease in 14C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (BRAF- and PI3KCA-wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit PI3KCA-mutant CRC cases, which currently have a poor prognostic.


Subject(s)
Aspirin , Cell Movement , Cell Proliferation , Colorectal Neoplasms , Metformin , Humans , Metformin/pharmacology , Aspirin/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cell Proliferation/drug effects , Caco-2 Cells , Cell Movement/drug effects , HT29 Cells , Mutation , Drug Synergism , Cell Survival/drug effects , Antineoplastic Agents/pharmacology , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Cell Line, Tumor
5.
Compr Rev Food Sci Food Saf ; 23(3): e13351, 2024 05.
Article in English | MEDLINE | ID: mdl-38682674

ABSTRACT

Consumer priorities in healthy diets and lifestyle boosted the demand for nutritious and functional foods as well as plant-based ingredients. Avocado has become a food trend due to its nutritional and functional values, which in turn is increasing its consumption and production worldwide. Avocado edible portion has a high content of lipids, with the pulp and its oil being rich in monounsaturated fatty acids and essential omega - 3 and omega - 6 polyunsaturated fatty acids (PUFA). These fatty acids are mainly esterified in triacylglycerides, the major lipids in pulp, but also in minor components such as polar lipids (phospholipids and glycolipids). Polar lipids of avocado have been overlooked despite being recently highlighted with functional properties as well. The growth in the industry of avocado products is generating an increased amount of their byproducts, such as seed and peels (nonedible portions), still undervalued. The few studies on avocado byproducts pointed out that they also contain interesting lipids, with seeds particularly rich in polar lipids bearing PUFA, and thus can be reused as a source of add-value phytochemical. Mass spectrometry-based lipidomics approaches appear as an essential tool to unveil the complex lipid signature of avocado and its byproducts, contributing to the recognition of value-added lipids and opening new avenues for their use in novel biotechnological applications. The present review provides an up-to-date overview of the lipid signature from avocado pulp, peel, seed, and its oils.


Subject(s)
Lipidomics , Lipids , Persea , Persea/chemistry , Lipidomics/methods , Lipids/chemistry , Lipids/analysis , Nutritive Value , Fruit/chemistry , Seeds/chemistry
6.
Curr Opin Plant Biol ; 78: 102527, 2024 04.
Article in English | MEDLINE | ID: mdl-38484440

ABSTRACT

Cell size affects many processes, including exchange of nutrients and external signals, cell division and tissue mechanics. Across eukaryotes, cells have evolved mechanisms that assess their own size to inform processes such as cell cycle progression or gene expression. Here, we review recent progress in understanding plant cell size regulation and its implications, relating these findings to work in other eukaryotes. Highlights include use of DNA contents as reference point to control the cell cycle in shoot meristems, a size-dependent cell fate decision during stomatal development and insights into the interconnection between ploidy, cell size and cell wall mechanics.


Subject(s)
Plant Cells , Plants , Cell Cycle/genetics , Cell Division , Cell Differentiation/genetics , Plants/genetics , Ploidies , Cell Size , Gene Expression Regulation, Plant/genetics
7.
Glia ; 72(6): 1096-1116, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38482984

ABSTRACT

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2AR or CB1R-A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.


Subject(s)
Astrocytes , Cannabinoids , Mice , Animals , Receptors, Cannabinoid , Receptor, Adenosine A2A , Neuronal Plasticity , Receptor, Cannabinoid, CB1/genetics
8.
Neurobiol Dis ; 193: 106435, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38336279

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1G93A mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1G93A mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.


Subject(s)
Amyotrophic Lateral Sclerosis , Motor Cortex , Neurodegenerative Diseases , Mice , Animals , Astrocytes/metabolism , Amyotrophic Lateral Sclerosis/metabolism , Superoxide Dismutase-1/genetics , Superoxide Dismutase-1/metabolism , Mice, Transgenic , Neurodegenerative Diseases/metabolism , Proteomics , Disease Models, Animal , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
9.
J Pain Symptom Manage ; 67(5): e439-e452, 2024 May.
Article in English | MEDLINE | ID: mdl-38237790

ABSTRACT

CONTEXT: The place where people are cared towards the end of their life and die is a complex phenomenon, requiring a deeper understanding. Honoring preferences is critical for the delivery of high-quality care. OBJECTIVES: In this umbrella review we examine and synthesize the evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS: Following the Joanna Briggs Institute methodology, we conducted a comprehensive search for systematic reviews in PsycINFO, MEDLINE, EMBASE, CINAHL, Epistemonikos, and PROSPERO without language restrictions. RESULTS: The search identified 15 reviews (10 high-quality, three with meta-analysis), covering 229 nonoverlapping primary studies. Home is the most preferred place of end-of-life care for both patients (11%-89%) and family members (23%-84%). It is also the most preferred place of death (patient estimates from two meta-analyses: 51%-55%). Hospitals and hospice/palliative care facilities are preferred by substantial minorities. Reasons and factors affecting preferences include illness-related, individual, and environmental. Differences between preferred places of care and death are underexplored and the evidence remains inconclusive about changes over time. Congruence between preferred and actual place of death ranges 21%-100%, is higher in studies since 2004 and a meta-analysis shows noncancer patients are at higher risk of incongruence than cancer patients (OR 1.23, 95% CI: 1.01-1.49, I2 = 62%). CONCLUSION: These findings are a crucial starting point to address gaps and enhance strategies to align care with patient and family preferences. To accurately identify patient and family preferences is an important opportunity to change their lives positively.


Subject(s)
Hospice Care , Terminal Care , Humans , Palliative Care/methods , Systematic Reviews as Topic , Terminal Care/methods , Family , Patient Preference , Attitude to Death
11.
J Clin Endocrinol Metab ; 109(3): e1117-e1124, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-37888829

ABSTRACT

CONTEXT: We recently reported that the presence of glutamic acid decarboxylase antibodies (GADA) was not associated with large-for-gestational-age infants in women with hyperglycemia in pregnancy (HIP). OBJECTIVE: We explored the association between the presence of GADA and other HIP-related adverse pregnancy outcomes. METHODS: This observational prospective study, conducted at a university hospital in a suburb of Paris, France, included 1182 consecutive women with HIP measured for GADA at HIP care initiation between 2012 and 2017. Post hoc analyses for outcomes included gestational weight gain, insulin therapy, cesarean delivery, hypertensive disorders, small-for-gestational-age infant, prematurity, and neonatal hypoglycemia. RESULTS: Of the 1182 women studied, 87 (7.4%) had positive (≥ 1 IU/mL) GADA. Although socioeconomic, clinical, and biological characteristics were similar across women in the positive and negative GADA groups, higher fasting plasma glucose values during early HIP screening were observed in the former (5.5 ± 1.5 vs 5.2 ± 0.7 mmol/L respectively, P < .001). At HIP care initiation, fructosamine levels were higher in women with positive GADA (208 ± 23 vs 200 ± 18 µmol/L; P < .05). In the homeostatic model assessment, insulin resistance (HOMA-IR) and beta secretion (HOMA-B) rates were similar in both groups. Gestational weight gain and the rates of all adverse outcomes were similar in both groups except for cesarean delivery (18.4 and 27.3% for positive and negative GADA, respectively; adjusted odds ratio 0.49 [95% CI, 0.26-0.92], P = .026). CONCLUSION: Universal measurement of GADA in women with HIP highlighted that 7.4% had positive GADA. No association was observed between GADA and HIP-related adverse pregnancy outcomes, except a lower risk of cesarean delivery.


Subject(s)
Diabetes, Gestational , Gestational Weight Gain , Hyperglycemia , Pregnancy , Infant, Newborn , Humans , Female , Glutamate Decarboxylase , Prospective Studies , Autoantibodies , Prognosis , Pregnancy Outcome/epidemiology
12.
Int J Biol Macromol ; 255: 128210, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37992936

ABSTRACT

The 5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin (TDFPPS4) was reported as a potential photosensitizer for photodynamic therapy. The capacity of the photosensitizers to be carried in the human bloodstream is predominantly determined by its extension of binding, binding location, and binding mechanism to human serum albumin (HSA), influencing its biodistribution and ultimately its photodynamic therapy efficacy in vivo. Thus, the present work reports a biophysical characterization on the interaction between the anionic porphyrin TDFPPS4 and HSA by UV-visible absorption, circular dichroism, steady-state, time-resolved, and synchronous fluorescence techniques under physiological conditions, combined with molecular docking calculations and molecular dynamics simulations. The interaction HSA:TDFPPS4 is spontaneous (ΔG° < 0), strong, and enthalpically driven (ΔH° = -70.1 ± 3.3 kJ mol-1) into subdomain IIA (site I). Curiously, despite the porphyrin binding into an internal pocket, about 50 % of TDFPPS4 structure is still accessible to the solvent, making aggregation in the bloodstream possible. In silico calculations were reinforced by spectroscopic data indicating porphyrin aggregation between bound and unbound porphyrins. This results in an adverse scenario for anionic porphyrins to achieve their therapeutical potential as photosensitizers and control of effective dosages. Finally, a trend of anionic porphyrins to have a combination of quenching mechanisms (static and dynamic) was noticed.


Subject(s)
Porphyrins , Serum Albumin, Human , Humans , Serum Albumin, Human/chemistry , Photosensitizing Agents/pharmacology , Molecular Docking Simulation , Binding Sites , Water/chemistry , Porphyrins/chemistry , Tissue Distribution , Protein Binding , Spectrometry, Fluorescence , Circular Dichroism , Thermodynamics
13.
Int J Palliat Nurs ; 29(12): 571-577, 2023 Dec 02.
Article in English | MEDLINE | ID: mdl-38085617

ABSTRACT

BACKGROUND: To describe the use of a telephone consultation (TC) hotline for palliative care (PC) patients and their families at home provided by a PC service, during the COVID-19 lockdown. METHODS: Observational and cross-sectional study of a TC hotline performed by a PC service from 1 January to 31 December 2020. Data was collected through a record sheet completed during the call. Descriptive analyses were performed using the SPSS software (V.21 for Windows). RESULTS: A total of 494 calls were retrieved (n=187 patients; 6500 minutes recorded). Compared to 2019, incoming calls increased 33.8%. Most callers were a family member (n=419) or a community health worker (n= 60). The peak of calls was registered in April (13.5%), May (13.2%) and October (15.0%). Main problems included uncontrolled symptoms (81.9%), need for medication (8.6%), information (4.8%) and consultation rescheduling (2.6%). In 81.9% of the cases, the call occurred during a crisis. The PC team solved 92.9% of the problems. Only 20 patients were admitted in the emergency department (this was 30.5% less compared to 2019). CONCLUSIONS: The TC is a feasible alternative to traditional in-person follow-ups. Callers considered it very useful, especially during the COVID-19 lockdown. Communication was improved and admissions to emergency services were reduced.


Subject(s)
COVID-19 , Palliative Care , Humans , Hotlines , Referral and Consultation , Cross-Sectional Studies , Telephone
14.
Rev Gaucha Enferm ; 44: e20230080, 2023.
Article in English, Portuguese | MEDLINE | ID: mdl-38055462

ABSTRACT

OBJECTIVE: To conduct the cross-cultural adaptation and evaluate the evidence of content validity of the Adverse Events Associated with Nursing Practices instrument in the Brazilian context. METHOD: Psychometric study, conducted between June 2021 and February 2023, following the stages of the Patient-Reported Outcomes Measurement Information System protocol. Semantic, idiomatic, experimental and conceptual equivalences were evaluated, along with content validity evidence, considering Content Validity Ratio (CVR) parameters, with the participation of 25 experts. RESULTS: A Brazilian version with 55 items was obtained, demonstrating good linguistic equivalence to the original version (agreement rate=99.2%), and adjustments in the items writing. CVR values remained above 0.60. Cognitive testing indicated good understanding, confirmed by the 31 participants in this stage, with a short application time (average = 17 minutes). CONCLUSION: The final version of the instrument showed good linguistic equivalence, strong evidence of content validity and a good response process in the Brazilian context.


Subject(s)
Cross-Cultural Comparison , Translations , Humans , Surveys and Questionnaires , Language , Brazil , Reproducibility of Results
16.
Nurse Educ Pract ; 73: 103829, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37977039

ABSTRACT

OBJECTIVE: To summarize the effects of spiritual intelligence (SI) training in several contexts and to identify the most consensual patterns in SI intervention design. INTRODUCTION: The "adaptive application" of spirituality in life is called SI, the ability to use spirituality in everyday problem-solving and it is proven to relate to better clinical and spiritual care (SC) competency in healthcare professionals. Interventions aiming to increase SI have been tested in different settings with benefits that can have a significant impact on the way healthcare professionals approach SC. INCLUSION CRITERIA: It included any quantitative studies that used reproducible methodology and reported on the implementation of interventions aiming to increase SI. Text, proceedings, conference or opinion papers, abstracts, reviews, mixed methods and qualitative studies were excluded from this scoping review. METHODS: Scoping review of quantitative studies on "spiritual intelligence" (query term) that include SI intervention programs (inclusion criteria) conducted on PubMed Central, Scopus, Web Of Science and PsycInfo databases, using the Joanna Briggs Institute methodology. Studies published until the 1st january 2022 were included. The studies' selection, extraction and synthesis of data was carried out by two independent reviewers. RESULTS: From the 10 articles/studies included, six were quasi-experimental and three experimental. Most (n=9) were conducted in Iran. The most common target samples of the studies were nurses (4 studies) and students (4 studies). SI training protocols, although based in group sessions, varied in their content between the different studies. SI interventions reported significant increase of SI levels, improvement of communications skills and reduction of anxiety, stress and depression levels. CONCLUSIONS: Despite the consensus among studies regarding the benefits of spiritual intelligence programs, more studies are needed to gauge long-term outcomes. There is also a need to standardize training protocols in spiritual intelligence.


Subject(s)
Health Personnel , Spirituality , Humans , Anxiety , Intelligence , Iran
17.
BMC Pregnancy Childbirth ; 23(1): 740, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853313

ABSTRACT

BACKGROUND: In women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators-food insecurity and poor language proficiency-on adherence to prenatal care and maternal and fetal outcomes. METHODS: In a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes. RESULTS: Among the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency. CONCLUSION: We found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.


Subject(s)
Hyperglycemia , Insulins , Pregnancy Complications , Pregnancy , Infant, Newborn , Female , Humans , Infant, Small for Gestational Age , Fetal Development , Pregnancy Outcome/epidemiology , Birth Weight , Hyperglycemia/epidemiology , Pregnancy Complications/epidemiology
18.
Photochem Photobiol Sci ; 22(11): 2607-2620, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37755667

ABSTRACT

The COVID-19 pandemic exposes our vulnerability to viruses that acquire the ability to infect our cells. Classical disinfection methods are limited by toxicity. Existing medicines performed poorly against SARS-CoV-2 because of their specificity to targets in different organisms. We address the challenge of mitigating known and prospective viral infections with a new photosensitizer for antimicrobial photodynamic therapy (aPDT). Photodynamic inactivation is based on local oxidative stress, which is particularly damaging to enveloped viruses. We synthesized a cationic imidazolyl chlorin that reduced by > 99.999% of the percentage inhibition of amplification of SARS-CoV-2 collected from patients at 0.2 µM concentration and 4 J cm-2. Similar results were obtained in the prevention of infection of human ACE2-expressing HEK293T cells by a pseudotyped lentiviral vector exhibiting the S protein of SARS-CoV-2 at its surface. No toxicity to human epidermal keratinocytes (HaCaT) cells was found under similar conditions. aPDT with this chlorin offers fast and safe broad-spectrum photodisinfection and can be repeated with low risk of resistance.


Subject(s)
Anti-Infective Agents , Photochemotherapy , Humans , Photosensitizing Agents/chemistry , Disinfection , Pandemics , HEK293 Cells , Prospective Studies , Photochemotherapy/methods , SARS-CoV-2 , Antiviral Agents/pharmacology
19.
Diabetes Metab ; 49(5): 101469, 2023 09.
Article in English | MEDLINE | ID: mdl-37648077

ABSTRACT

AIM: Prognosis of treated hyperglycemia in pregnancy (HIP) may differ according to whether diagnosis following an oral glucose tolerance test (OGTT) is based on high fasting and/or high post-load glucose values. METHODS: From a multiethnic prospective study, we included 8,339 women screened for HIP after 22 weeks of gestation. We evaluated the risk of large-for-gestational-age (LGA) infant (primary endpoint) and other adverse pregnancy outcomes according to HIP status in four groups defined as follows: no HIP (n = 6,832, reference); isolated fasting HIP (n = 465), isolated post-load HIP (n = 646), and fasting and post-load HIP (n = 396). RESULTS: After adjusting for age, body mass index, ethnicity, smoking during pregnancy and parity, compared with no HIP, the adjusted odds ratios [95% confidence interval] for LGA infant were higher in the isolated fasting HIP (1.47 [1.11-1.96]) and fasting and post-load HIP (1.65 [1.23-2.21]) groups, but not in the isolated post-load HIP (1.13 [0.86-1.48]) group. The adjusted odds ratios for preterm delivery and neonatal intensive care unit were higher in the post-load HIP group (1.44 [1.03-2.03] and 1.28 [1.04-1.57], respectively), the fasting and post-load HIP group (1.81 [1.23-2.68] and 1.42 [1.10-1.81], respectively) but not in the isolated fasting HIP group (1.34 [0.90-2.00] and 1.20 [0.94-1.52], respectively). CONCLUSION: Despite glucose-lowering care and adjustment for confounders, compared with no HIP, fasting HIP was associated with a higher rate of LGA infant, whereas post-load HIP was associated with higher preterm delivery and neonatal intensive care unit admission rates.


Subject(s)
Diabetes, Gestational , Hyperglycemia , Premature Birth , Pregnancy , Infant, Newborn , Female , Humans , Pregnancy Outcome/epidemiology , Diabetes, Gestational/epidemiology , Diabetes, Gestational/diagnosis , Glucose , Premature Birth/epidemiology , Prospective Studies , Birth Weight , Blood Glucose , Hyperglycemia/epidemiology , Hyperglycemia/diagnosis , Fasting
20.
Chemistry ; 29(53): e202301442, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37606898

ABSTRACT

A new fluorinated manganese porphyrin, (Mn-TPP-p-CF3 ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual 1 H relaxivity and 19 F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d6 /H2 O evidenced that the 1 H relaxometric and 19 F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (dMn-F =9.7-10 Å), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on 19 F T1 and T2 relaxation times. Mn-TPP-p-CF3 has a reversible Mn(II)/Mn(III) redox potential of 0.574 V vs. NHE in deoxygenated aqueous HEPES/ THF solution. The reduction of Mn(III)-TPP-p-CF3 in the presence of ascorbic acid is slowly, but fully reversed in the presence of air oxygen, as monitored by UV-Vis spectrometry and 19 F NMR. The broad 1 H and 19 F NMR signals of Mn(III)-TPP-p-CF3 disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened 19 F NMR signal from Mn(II)-TPP-p-CF3 . Phantom 19 F MR images in DMSO show a MRI signal intensity decrease upon reduction of Mn(III)-TPP-p-CF3 , retrieved upon complete reoxidation in air within ~24 h. 1 H NMRD curves of the Mn(III)/(II)-TPP-p-CF3 chelates in mixed DMSO/water solvent have the typical shape of Mn(II)/Mn(III) porphyrins.

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