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1.
Environ Int ; 192: 108991, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39299052

RESUMEN

Chemical risk assessments typically focus on single substances, often overlooking real-world co-exposures to chemical mixtures. Mixture toxicology studies using representative mixtures can reveal potential chemical interactions, but these do not account for the unique chemical profiles that occur in the blood of diverse individuals. Here we used the H295R steroidogenesis assay to screen personalized mixtures of 24 persistent organic pollutants (POPs) for cytotoxicity and endocrine disruption. Each mixture was reconstructed at a human exposure relevant concentration (1×), as well as at 10- and 100-fold higher concentration (10×, 100×) by acoustic liquid handling based on measured blood concentrations in a Swedish cohort. Among the twelve mixtures tested, nine mixtures decreased the cell viability by 4-18%, primarily at the highest concentration. While the median and maximum mixtures based on the whole study population induced no measurable effects on steroidogenesis at any concentration, the personalized mixture from an individual with the lowest total POPs concentration was the only mixture that affected estradiol synthesis (35% increase at the 100× concentration). Mixtures reconstructed from blood levels of three different individuals stimulated testosterone synthesis at the 1× (11-15%) and 10× concentrations (12-16%), but not at the 100× concentration. This proof-of-principle personalized toxicity study illustrates that population-based representative chemical mixtures may not adequately account for the toxicological risks posed to individuals. It highlights the importance of testing a range of real-world mixtures at relevant concentrations to explore potential interactions and non-monotonic effects. Further toxicological studies of personalized contaminant mixtures could improve chemical risk assessment and advance the understanding of human health, as chemical exposome data become increasingly available.

2.
Sci Total Environ ; : 176298, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39299307

RESUMEN

This study aims to investigate the meteorological variables determining Cupressaceae pollen grain disruption in the environment. A parallel sampling of pollen grains and disrupted Cupressaceae pollen grains was performed in six cities using two Spanish aerobiological networks. The pollen concentrations, disrupted pollen concentrations, percentage of disrupted pollen and number of days when the percentage of disrupted pollen was above or equal to 50 % were quantified during two pollen seasons. The concentrations were determined following the standardised method EN 16868. Results show that the concentrations of pollen grains and disrupted pollen grains were not determined by geographical features and rarely by bioclimatic variables or indexes but by the ornamental use of the specimens in the vicinity of the pollen sampler, highlighting the possibility of using management practices to reduce exposure to allergens in the cities. African dust outbreaks coincided with higher concentrations of pollen grains and disrupted pollen grains, but the reduced percentage of disrupted pollen grains pointed to a non-causal relationship with long-distance transport. The effect of wind and maximum gusts remained negligible. The triggering factor for pollen disruption was the amount of water in the atmosphere, mainly reported as relative humidity. Rainfall increased the effect of disruption due to pollen grain swelling caused by its wash-out effect. The higher the relative humidity, the higher the disrupted pollen concentrations. This aligns with the mechanism of Cupressaceae reproduction since the family needs a water medium in the form of pollination droplets for the pollination tube to develop and the pollen grain to perform its biological function. Therefore, people that develop allergic symptoms to Cupresaceae pollen should avoid exposure during days with high relative humidity in the main pollen season.

3.
BMC Public Health ; 24(1): 2555, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300419

RESUMEN

BACKGROUND: Working during the night interferes with the timing of normal daily activities and is associated with an increased risk of chronic diseases. Under controlled experimental conditions, interventions focusing on sleep and nutrition can mitigate the short-term adverse effects of shift work. However, it is unclear how these results translate to real-life, how they can be targeted to individual conditions, and how they relate to long-term health. Therefore, the current study aims to implement a personalized sleep and nutritional intervention among night shift workers in the field. METHODS: A non-blinded controlled intervention study is used, consisting of a run-in period, an intervention of 3 months, post-intervention measurements, and a follow-up after 12 months. Three study arms are included: sleep intervention, nutritional intervention, and control group (n = 25 each). Participants are healthy 18-60-year male night shift workers, with at least one year of experience in night shift work. Information from the run-in period will be used to personalize the interventions. The main outcomes are sleep measurements and continuous interstitial glucose levels. Furthermore, general health biomarkers and parameters will be determined to further evaluate effects on long-term health. DISCUSSION: This study aims to mitigate negative health consequences associated with night shift work by introducing two personalized preventive interventions. If proven effective, the personalized interventions may serve as practical solutions that can have a meaningful impact on the sustainable health and employability of night shift workers. This study will thereby contribute to the current need for high-quality data on preventative strategies for night shift work in a real-life context. TRIAL REGISTRATION: This trial has been registered under ClinicalTrials.gov Identifier NCT06147089. Registered 27 November 2023.


Asunto(s)
Horario de Trabajo por Turnos , Sueño , Humanos , Masculino , Adulto , Persona de Mediana Edad , Adulto Joven , Sueño/fisiología , Adolescente , Trastornos del Sueño del Ritmo Circadiano/prevención & control , Tolerancia al Trabajo Programado/fisiología
4.
Front Endocrinol (Lausanne) ; 15: 1459329, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301317

RESUMEN

Introduction: Currently, although there have been a few reports on the endocrine-disrupting effects of neonicotinoids, the effect on Chironomidae during long-term exposure remains unknown. Methods: Ecdysis and sex ratio, along with ecdysone-relevant gene expressions of representative neonicotinoid dinotefuran on Chironomus kiinensis were investigated at different environmental concentrations by long-term exposure. Results: A low dose of dinotefuran delayed pupation and emergence via inhibiting ecdysis. Sex ratios of adults shifted toward male-dominated populations with the concentration of dinotefuran increasing. The corresponding transcriptions of ecdysis genes ecr, usp, E74, and hsp70 were significantly downregulated in the midge. For estrogen effects, the vtg gene expression was upregulated, but there was no significant change for the err gene. Discussion: These results would improve our understanding of the endocrine-disrupting mechanisms of neonicotinoid insecticides to Chironomidae and provide data support for assessing their potential environmental risks.


Asunto(s)
Chironomidae , Disruptores Endocrinos , Guanidinas , Neonicotinoides , Nitrocompuestos , Razón de Masculinidad , Animales , Neonicotinoides/toxicidad , Chironomidae/efectos de los fármacos , Chironomidae/genética , Chironomidae/metabolismo , Masculino , Nitrocompuestos/toxicidad , Disruptores Endocrinos/toxicidad , Femenino , Guanidinas/toxicidad , Muda/efectos de los fármacos , Insecticidas/toxicidad , Larva/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos
5.
Digit Health ; 10: 20552076241226964, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286786

RESUMEN

Objective: The goal of this research was to demonstrate the efficacy of telemedicine via design, implementation and evaluation of a web-based remote patient monitoring system (WB-RPMS) across the tertiary/university teaching hospitals in a developing country Nigeria, as a tool to continue to expand access to an affordable and resilient tertiary healthcare system through the challenging times of the COVID-19 pandemic or any future disruptions. Methods: This research employed an agile and human-centred design thinking philosophy, which saw the researchers iteratively collaborate with clinicians across the system development value chain. It also employed qualitative and quantitative research methods for new system evaluations. After the system's development, a 20-patient sample was randomly selected from members of the National Youth Service Corp to evaluate the WB-RPMS Patient Portal for usability and user experience through a survey based on the system usability scale. Again, the COREQ standards for reporting research result were adopted for this study. Results: The evaluation of the WB-RPMS Patient Portal by a select patient sample showed that 95.0% of the respondents believed that they would like to use the system frequently. It was also discovered that 90.0% of all respondents also indicated that they found the Patient Portal to be simple; 85.0% of the respondents believed and indicated that the WB-RPMS Patient Portal was easy to use. Conclusions: The result of the usability evaluation of the developed WB-RPMS Patient Portal showed that it was well received by the select patient sample and by the clinicians who participated in the development process. In fact, the performance of the system shows that it has the potential to remotely support and sustain improved access to affordable healthcare for outpatients in developing countries even during times of uncertainties and disruptions as recently occasioned by COVID-19 pandemic.

6.
Environ Sci Technol ; 58(37): 16336-16346, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39226441

RESUMEN

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9-16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.


Asunto(s)
Pubertad , Humanos , Masculino , Noruega , Adolescente , Niño , Fluorocarburos/sangre , Contaminantes Ambientales/sangre , Estudios Transversales , Exposición a Riesgos Ambientales , Ácidos Alcanesulfónicos/sangre
7.
Environ Sci Pollut Res Int ; 31(43): 55708-55719, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39243328

RESUMEN

Endocrine-disrupting chemicals (EDCs) are widespread pollutants known to interfere with hormonal pathways and to disrupt behaviours. Standardised behavioural procedures have been developed in common fish model species to assess the impact of various pollutants on behaviours such as locomotor activity and anxiety-like as well as social behaviours. These procedures need now to be adapted to improve our knowledge on the behavioural effects of EDCs on less studied marine species. In this context, the European sea bass (Dicentrarchus labrax) is emerging as a valuable species representative of the European marine environment. Here, we designed and validated a two-step procedure allowing to sequentially assess anxiety-like behaviours (novel tank test) and social preference (visual social preference test) in sea bass. Thereafter, using this procedure, we evaluated whether social behavioural disruption occurs in 2-month-old larvae after an 8-day exposure to a xenoestrogen, the 17α-ethinylestradiol (EE2 at 0.5 and 50 nM). Our results confirmed previous studies showing that exposure to 50 nM of EE2 induces a significant increase in anxiety-like behaviours in sea bass larvae. On the contrary, social preference seemed unaffected whatever the EE2 concentration, suggesting that social behaviour has more complex mechanical regulations than anxiety.

8.
Chemosphere ; 365: 143287, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39243900

RESUMEN

Active ingredients of pesticides or biocides and industrial chemicals can negatively affect environmental organisms, potentially endangering populations and ecosystems. European legislation mandates that chemical manufacturers provide data for the environmental risk assessment of substances to obtain registration. Endocrine disruptors, substances that interfere with the hormone system, are not granted marketing authorization due to their adverse effects. Current methods for identifying disruptors targeting the thyroid hormone system are costly and require many amphibians. Consequently, alternative methods compliant with the 3R principle (replacement, reduction, refinement) are essential to prioritize risk assessment using reliable biomarkers at non-protected life stages. Our study focused on detecting robust biomarkers for thyroid-disrupting mechanisms of action (MoA) by analyzing molecular signatures in zebrafish embryos induced by deiodinase inhibitor iopanoic acid and thyroid peroxidase inhibitor methimazole. We exposed freshly fertilized zebrafish eggs to these compounds, measuring lethality, hatching rate, swim bladder size and transcriptomic responses. Both compounds significantly reduced swim bladder size, aligning with prior findings. Transcriptome analysis revealed specific molecular fingerprints consistent with the MoA under investigation. This analysis confirmed regulation directions seen in other studies involving thyroid disruptors and allowed us to identify genes like tg, scl2a11b, guca1d, cthrc1a, si:ch211-226h7.5, soul5, nnt2, cox6a2 and mep1a as biomarker genes for thyroid disrupting MoA in zebrafish embryos as per OECD test guideline 236. Future screening methods based on our findings will enable precise identification of thyroid-related activity in chemicals, promoting the development of environmentally safer substances. Additionally, these biomarkers could potentially be incorporated into legally mandated chronic toxicity tests in fish, potentially replacing amphibian tests for thyroid disruption screening in the future.

9.
J Control Release ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293527

RESUMEN

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo.

10.
Genomics ; : 110938, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293535

RESUMEN

Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.

11.
Br J Pharmacol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294926

RESUMEN

BACKGROUND AND PURPOSE: Ulinastatin has beneficial effects in patients undergoing coronary artery bypass grafting (CABG) surgery due to its anti-inflammatory properties, but the underlying mechanism remains unclear. EXPERIMENTAL APPROACH: We used samples from patients undergoing CABG, a model of cardiac ischaemia-reperfusion injury (IRI) in mice and murine cardiac endothelial cell cultures to investigate links between ulinastatin, the kallikrein-kinin system (KKS), endothelial dysfunction and cardiac inflammation in the response to ischaemia/reperfusion injury (IRI). These links were assessed using clinical investigations, in vitro and in vivo experiments and RNA sequencing analysis. KEY RESULTS: Ulinastatin inhibited the activity of tissue kallikrein, a key enzyme of the KKS, at 24 h after CABG surgery, which was verified in our murine cardiac ischaemia-reperfusion model. Under normal conditions, ulinastatin only inhibited kallikrein activity but did not affect bradykinin (B1/B2) receptors. Ulinastatin protected against IRI, in vivo and in vitro, by suppressing activation of the kallikrein-kinin system and down-regulating B1/B2 receptor-related signalling pathways including ERK/ iNOS, which resulted in enhanced endothelial barrier function, mitigation of inflammation and oedema, decreased infarct size, improved cardiac function and decreased mortality. Inhibition of kallikrein and knockdown of B1, but not B2 receptors prevented ERK translocation into the nucleus, reducing reperfusion-induced injury in murine cardiac endothelial cells. CONCLUSIONS AND IMPLICATIONS: Treatment with ulinastatin exerts a protective influence on cardiac reperfusion by suppressing activation of the kallikrein-kinin system. Our findings highlight the potential of targeting kallikrein /bradykinin receptors to alleviate endothelial dysfunction, thus improving cardiac IRI.

12.
J Appl Toxicol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39295171

RESUMEN

The reliability of relative quantification RT-qPCR depends upon the gene of interest being normalized to one or more reference genes, with the assumption that the chosen reference genes do not experience altered expression with experimental conditions. The correct choice of stable reference genes is critical when investigating alterations to gene transcript levels following exposure to endocrine and metabolic disrupting chemicals, such as the flame retardant triphenyl phosphate (TPhP). This study assessed the stability of eight reference genes following TPhP exposure in embryonic cells derived from rainbow trout (Oncorhynchus mykiss). The genes ß-actin (actb) and 18s rRNA (18s) were stable, while glyceraldehyde-3-phosphate dehydrogenase (gapdh) relative expression was found to be increased. gapdh is a popular reference gene and has been previously used in the literature for investigating TPhP exposure in teleost fish models. We discuss the implications of gapdh upregulation in the context of TPhP as a metabolic disrupting chemical. Furthermore, we quantified the expression of the tumor suppressor gene p53 following TPhP exposure in relation to different reference genes to use as an example to report on how discrepancies in findings might arise depending on the stability of the chosen reference gene.

13.
Radiol Case Rep ; 19(11): 4845-4848, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39234009

RESUMEN

Isolated colon injuries following blunt abdominal trauma have been reported at a rate of 0.1%-0.5%, with isolated sigmoid colon injuries involved in only 34.8% of single colon injuries. Surgical treatment options include recto-colonic anastomosis, resection with or without recto-colonic anastomosis, and colostomy. We report the case of a 39-year-old male patient diagnosed with isolated sigmoid colon rupture after a traffic accident, identified using contrast-enhanced abdominal computed tomography. The patient underwent emergency surgery, during which the Hartmann procedure was performed. This included excision of the sigmoid colon at both ends of the hiatus, creation of a proximal colostomy, closure of the distal end, and repair of the sigmoid disruption segment. Seven days after surgery, the patient's clinical symptoms were stable, and he was discharged.

14.
BMC Microbiol ; 24(1): 317, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223475

RESUMEN

BACKGROUND: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans. RESULTS: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively. CONCLUSION: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture.


Asunto(s)
Bacillus amyloliquefaciens , Enterobacteriaceae , Panax , Enfermedades de las Plantas , Raíces de Plantas , Panax/microbiología , Panax/química , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/química , Bacillus amyloliquefaciens/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Raíces de Plantas/microbiología , Enterobacteriaceae/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Microbiología del Suelo , Rizosfera , Acetatos/farmacología , Ascomicetos/efectos de los fármacos , Ascomicetos/química , Antifúngicos/farmacología , Antifúngicos/metabolismo , Agentes de Control Biológico/farmacología
15.
Ultrasound Med Biol ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39277462

RESUMEN

OBJECTIVE: Tamoxifen is the most used agent to treat estrogen receptor-positive (ER+) breast cancer (BC). While it decreases the risk of cancer recurrence by 50%, many patients develop resistance to this treatment, culminating in highly aggressive disease. Tamoxifen resistance comes from the repression of ER transcriptional activity that switches the cancer cells to proliferation via nonhormonal signaling pathways. Here, we evaluate a potential strategy to overcome tamoxifen resistance by focused ultrasound (FUS), a noninvasive approach for the mechanical excitation of cancer cells. METHODS: Resistant and nonresistant ER+ BC cells and xenografts from patients with ER+ BC were treated with tamoxifen, FUS or their combination. The apoptosis, proliferation rate, gene expression and activity of estrogen receptor, and morphological changes were measured in treated cells and tissues. RESULTS: FUS caused the mechanical disruption of tamoxifen-resistant BC cells that in turn led to the upregulation of ERα-encoding gene expression and long-term re-sensitization of the cells to tamoxifen. Patient-derived xenografts treated with Tamoxifen and FUS demonstrated a significant reduction in tumor viability and proliferation and a strong structural damage to tumor cells and extracellular matrix. CONCLUSION: FUS can improve ER+ BC treatment by re-sensitizing the cancer cells to tamoxifen.

16.
Microb Pathog ; 196: 106931, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39288825

RESUMEN

The development of antibiotic resistance has caused significant health problems. Antimicrobial peptides (AMPs) are considered next-generation antibiotics. Protegrin-1 (PG-1) is a ß-hairpin AMP with a membrane-binding capacity. This study used twelve PG-1 analogs with different amino acid substitutions. Coarse-grained molecular dynamics (MD) simulations were used to assess these analogs, and their physicochemical properties were computed using the Antimicrobial Peptide Database. Three AMPs, PEP-D, PEP-C, and PEP-H, were chosen and synthesized for antibacterial testing. The microbroth dilution technique and hemolytic assays evaluated the antimicrobial efficacy and cellular toxicity. The checkerboard method was used to test the combined activity of AMP and standard antibiotics. Cell membrane permeability and electron microscopy were used to evaluate the mode of action. The chemical stability of the selective AMP, PEP-D, was assessed by a validated HPLC method. PEP-D consists of 16-18 amino acid residues and has a charge of +7 and a hydrophobicity of 44 %, similar to PG-1. It can efficiently inactivate bacteria by disrupting cell membranes and significantly reducing hemolytic activity. Chemical stability studies indicated that AMP was stable at 40 °C for six months under autoclave conditions. This study could introduce the potential therapeutic application of selective AMP as an anti-infective agent.

17.
Environ Toxicol Pharmacol ; 111: 104562, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245243

RESUMEN

Artificial turf, a consumer product growing in usage in the United States, contains diverse chemicals, some of which are endocrine disruptive. Endocrine effects from turf material extracts have been primarily limited to one component, crumb rubber, of these multi-material products. We present in vitro bioactivities from non-weathered and weathered turf sample extracts, including multiple turf components. All weathered samples were collected from real-world turf fields. Non-weathered versus weathered differentially affected the androgen (AR), estrogen (ER), glucocorticoid (GR), and thyroid receptors (TR) in reporter bioassays. While weathered extracts more efficaciously activated peroxisome proliferator activated receptor γ (PPARγ), this did not translate to greater in vitro adipogenic potential. All turf extracts activated the aryl hydrocarbon receptor (AhR). High AhR-efficacy extracts induced modest rat cardiomyoblast toxicity in an AhR-dependent manner. Our data demonstrate potential endocrine and cardiometabolic effects from artificial turf material extracts, warranting further investigation into potential exposures and human health effects.

18.
Prostaglandins Other Lipid Mediat ; 175: 106904, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39260818

RESUMEN

Transient receptor potential melastatin 7 (TRPM7) has been emerged as a potent drug target for immunomodulation with ion conductance and kinase activities. The research is projected to characterize the influences of TRPM7 on the course of ulcerative colitis (UC) and dissect the latent response mechanisms. The in vivo murine model and in vitro cell model of UC were both stimulated by DSS. RT-qPCR and western blotting tested the abundance of TRPM7. Colonic damage was estimated by Hematoxylin-eosin staining, calculation of colon length, measurement of DAI and MPO assay kit. CCK-8 method and TUNEL staining severally ascertained cell activity and apoptosis. ELISA method assayed the inflammatory levels and relevant assay kits determined oxidative stress levels. FITC-dextran flux, immunohistochemistry, TEER as well as western blotting evaluated intestinal barrier function. Immunofluorescence staining and western blotting appraised NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis. Depleted TRPM7 retarded inflammation, oxidative damage as well as intestinal barrier damage both in vitro and in vivo. TRPM7 reduction repressed the pyroptosis mediated by NLRP3 inflammasome. NLRP3 agonist nigericin partly abolished the protection elicited by TRPM7 silencing against inflammation, oxidative damage as well as intestinal barrier damage in vitro. Collectively, TRPM7 deletion might possess the therapeutic potential in UC, the working mechanism of which might involve the inactivation of NLRP3-dependent pyroptosis.

19.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39273373

RESUMEN

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing to OSA occurrence and development seems to be serotonin (5-HT). Currently, the research focuses on establishing and interlinking OSA pathogenesis and the severity of the disease on the molecular neurotransmitter omnipresent in the human body-serotonin, its pathway, products, receptors, drugs affecting the levels of serotonin, or genetic predisposition. The 5-HT system is associated with numerous physiological processes such as digestion, circulation, sleep, respiration, and muscle tone-all of which are considered factors promoting and influencing the course of OSA because of correlations with comorbid conditions. Comorbidities include obesity, physiological and behavioral disorders as well as cardiovascular diseases. Additionally, both serotonin imbalance and OSA are connected with psychiatric comorbidities, such as depression, anxiety, or cognitive dysfunction. Pharmacological agents that target 5-HT receptors have shown varying degrees of efficacy in reducing the Apnea-Hypopnea Index and improving OSA symptoms. The potential role of the 5-HT signaling pathway in modulating OSA provides a promising avenue for new therapeutic interventions that could accompany the primary treatment of OSA-continuous positive airway pressure. Thus, this review aims to elucidate the complex role of 5-HT and its regulatory mechanisms in OSA pathophysiology, evaluating its potential as a therapeutic target. We also summarize the relationship between 5-HT signaling and various physiological functions, as well as its correlations with comorbid conditions.


Asunto(s)
Serotonina , Transducción de Señal , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Serotonina/metabolismo , Animales , Receptores de Serotonina/metabolismo
20.
J Clin Med ; 13(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39274279

RESUMEN

Background: This study aimed to compare clinical outcomes and recurrence of instability after arthroscopic Bankart repair (ABR) in patients with anterior shoulder instability, with and without a GLAD lesion, while distinguishing between primary and recurrent instability. Methods: Consecutive patients who underwent isolated ABR between January 2012 and December 2021 were included. Patients with a concomitant GLAD lesion were matched in with patients without a GLAD lesion according to the following criteria: age, sex, BMI, follow-up time, and primary versus recurrent instability. At minimum two-year follow-up, the clinical outcome (Rowe score, redislocation rate) and the functional outcome, including the American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Shoulder Instability Index (WOSI), Oxford Shoulder Instability Score (OSIS), satisfaction (1-10 scale, 0 = unsatisfied, 10 = very satisfied), and Visual Analogue Scale (VAS), were compared between groups. Results: In total, 28 patients (14 GLAD vs. 14 Bankart; age: 32.5 ± 13.0 years; sex: 92.9% male; BMI: 24.6 ± 2.2) were included 6.9 ± 2.8 (2-11) years after isolated ABR (follow-up rate 63.6%). Clinical and functional outcome did not differ significantly between patients with versus without GLAD lesions (ASES score: 100 [96.5-100] vs. 97.5 [93.3-100], p = 0.27); WOSI (%): 9.0 [3.7-24.5] vs. 3.8 [0.8-8.9], p = 0.22; Rowe score: 90.0 [75.0-100] vs. 95.0 [78.8-100], p = 0.57; OSIS: 46 [44.7-48] vs. 46 [43.0-48], p = 0.54; satisfaction: 8.9 ± 1.4 vs. 8.0 ± 1.4, p = 0.78; VAS 0 [0-1.3] vs. 0 [0-1.0]. In both groups, two patients (14.3%) reported a redislocation during the observation period. Conclusions: At short- to mid-term follow-up, ABR showed favorable outcomes, low dislocation rates, and high patient satisfaction, regardless of the presence of a GLAD lesion or primary versus recurrent instability. However, follow-up time was heterogeneous, and the follow-up rate was marginal.

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