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1.
Heart Views ; 25(1): 50-51, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774546

RESUMO

Recent advances in coronary revascularization include total arterial grafting, however, in a few cases, harvesting the right internal thoracic artery (RITA) is not possible due to various reasons. In such cases, where the aorta is also calcified, few surgeons perform Y anastomosis configuration with the left internal thoracic artery(LITA) and saphenous vein which can have disastrous complications. Our patient is a 65-year-old man who was diagnosed with multivessel coronary disease and presented with a coronary steal during coronary artery bypass grafting surgery. The RITA was not harvested due to osteoporosis sternum. LITA-saphenous vein Y anastomosis configuration was done as the aorta was calcified. The anastomosis was done between the LITA to the left anterior descending (LAD) artery and the Y arm saphenous vein was anastomosed to an obtuse marginal (OM)branch. He developed coronary steal following anastomosis of the Y graft to the OM branch. The patient had ischemic changes inside the operation theatre in LAD territory, hence grafts were revised following which the patient became stable. There is a high possibility of a coronary steal when the caliber of the Y arm does not match with the LITA. LITA-saphenous vein Y anastomosis can cause more complications as the saphenous vein is much bigger in caliber compared to the LITA.

2.
Pharmaceutics ; 16(4)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38675125

RESUMO

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

3.
Indian Pediatr ; 61(5): 413-418, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38584403

RESUMO

OBJECTIVE: Acute encephalitis syndrome (AES) in children results in significant neurocognitive deficits or mortality. It is pertinent to study the AES patterns periodically to identify the changes in the etiological trends and outcomes. Our objective was to find the etiological agents of AES, mode of diagnosis, treatment given, and outcomes. METHODS: We reviewed the electronic records of children aged 1 month to 15 years who were admitted with AES in our centre from January 2015 to December 2019. We analyzed the the clinical, laboratory, and radiological profile of these children and adolescents in relation to their outcome. Poor outcome was defined as death, discharge against medical advice with neurological deficits, or Glasgow Outcome Score Extended (GOS-E) d≤ 5 at the time of discharge. RESULTS: Among 250 patients admitted with AES during the study period, a definitive etiological diagnosis was established in 56.4% of children (30.4% viral, 22% bacterial). Scrub typhus (11.2%) and dengue (9%) were the two most common underlying illnesses. Serology helped in clinching the diagnosis in 30% of children. A surge in AES cases in the post-monsoon season was observed in our cohort. Third-generation cephalosporin drugs (85.7%) and acyclovir (77.7%) were the most commonly used empiric antimicrobial drugs. About one-third of children (n = 80) had a poor outcome. GCS ≤ 8 at presentation and requirement for invasive ventilation were found to be significant predictors of poor outcome. CONCLUSION: A definitive diagnosis was obtained in about half of the children with AES. Viral (30.4%) and rickettsial infections (22%) were the common etiologies identified. Poor outcome was observed in 32% of patients.


Assuntos
Encefalopatia Aguda Febril , Humanos , Índia/epidemiologia , Criança , Adolescente , Pré-Escolar , Feminino , Masculino , Lactente , Encefalopatia Aguda Febril/epidemiologia , Encefalopatia Aguda Febril/diagnóstico , Estudos Retrospectivos
4.
J Med Chem ; 67(8): 6495-6507, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38608245

RESUMO

We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including the COVID-19 pandemic caused by SARS-CoV-2. Main protease (MPro), a highly conserved protease among various CoVs, is essential for viral replication and pathogenesis, making it a prime target for antiviral drug development. Here, we leverage proteolysis targeting chimera (PROTAC) technology to develop a new class of small-molecule antivirals that induce the degradation of SARS-CoV-2 MPro. Among them, MPD2 was demonstrated to effectively reduce MPro protein levels in 293T cells, relying on a time-dependent, CRBN-mediated, and proteasome-driven mechanism. Furthermore, MPD2 exhibited remarkable efficacy in diminishing MPro protein levels in SARS-CoV-2-infected A549-ACE2 cells. MPD2 also displayed potent antiviral activity against various SARS-CoV-2 strains and exhibited enhanced potency against nirmatrelvir-resistant viruses. Overall, this proof-of-concept study highlights the potential of targeted protein degradation of MPro as an innovative approach for developing antivirals that could fight against drug-resistant viral variants.


Assuntos
Antivirais , Proteases 3C de Coronavírus , Proteólise , SARS-CoV-2 , Humanos , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Proteólise/efeitos dos fármacos , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/antagonistas & inibidores , Células HEK293 , Descoberta de Drogas , Tratamento Farmacológico da COVID-19 , Células A549
5.
Lupus ; : 9612033241247358, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607271

RESUMO

Idiopathic intracranial hypertension (IIH) is a diagnosis of exclusion characterized by features of raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. Commonly used other terms for this entity include benign intracranial hypertension (BIH) or pseudotumor cerebri. Few case reports of systemic lupus erythematosus (SLE) presenting as IIH are available in the literature. We report a 12-year-old girl presented with chronic holocranial headache and occasional episodes of projectile vomiting for the last 6 months and then developed blurring of vision for the last month. She fulfilled the criteria for IIH. Subsequent evaluation revealed a diagnosis of SLE. The occurrence of IIH in SLE is not coincidental and is reported in 1%-5.4% of patients with SLE. Though corticosteroids have not been widely used in IIH, underlying SLE warranted administering corticosteroids with subsequent complete resolution of IIH. Pediatricians, neurologists, intensivists, and ophthalmologists should consider SLE as a differential diagnosis in children presenting with IIH.

6.
Heliyon ; 10(7): e28725, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596026

RESUMO

Environmental monitoring, ocean research, and underwater exploration are just a few of the marine applications that require precise underwater target localization. This study goes into the field of underwater target localization using Recurrent Neural Networks (RNNs) enhanced with proximity-based approaches, with a focus on mean estimation error as a performance metric. In complex and dynamic underwater environments, conventional localization systems frequently face challenges such as signal degradation, noise interference, and unstable hydrodynamic conditions. This paper presents a novel approach to employing RNNs to increase the accuracy of underwater target localization by exploiting the temporal dynamics of proximity-informed data. This method uses an RNN architecture to track changes in audio emissions from underwater targets sensed by a microphone network. Using the temporal correlations represented in the data, the RNN learns patterns indicative of target localization quickly and correctly. Furthermore, the addition of proximity-based features increases the model's ability to understand the relative distances between hydrophone nodes and the target, resulting in more accurate localization estimates. To evaluate the suggested methodology, thorough simulations and practical experiments were carried out in a variety of underwater environments. The results show that the RNN-based strategy beats conventional methods and works effectively even in difficult settings. The utility of the proximity-aware RNN model is demonstrated, in particular, by considerable reductions in the mean estimate error (MEE), an important performance measure.

7.
Int J Biol Macromol ; 265(Pt 2): 131128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537856

RESUMO

In this study, coaxial electrospinning is employed to make core-shell fibers, which represents a major advance in biomaterial innovation. Fibers that combine a protective shell and a therapeutic agent-loaded core, herald a revolutionary era in tissue engineering and wound care. Besides supporting cell growth, these fibers also preserve sterility, which makes them ideal for advanced wound dressings. We used embelin as the basis for this study because of its natural antibacterial properties. Its effectiveness in inhibiting the growth of bacteria made it the ideal candidate for our research. We have synthesized core-shell nanofibers that contain Sodium Alginate (SAL) in a Poly (ethylene oxide) (PEO) shell and Embelin in a Poly (3-hydroxybutyric acid) (PHB) core, which exhibit the homogeneity and flawless structure required for biomedical applications. When using SAL-PEO and EMB-PHB solutions dissolved in 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP), high consistency in results can be achieved. A biocompatibility study was conducted using NIH-3T3 fibroblasts, which demonstrated remarkable adhesion and proliferation, with over 95 % growth supporting both PHB + SAL-PEO and EMB-PHB + SAL-PEO fibers. In addition, the scaffold loaded with Embelin shows strong antibacterial activity and cytocompatibility. The combined activity demonstrates the potential of EMB-PHB + SAL-PEO fibers in wound healing, where tissue regeneration and preservation of sterility are crucial. The optimized concentration of Embelin within these scaffolds demonstrates robust antibacterial efficacy while exhibiting minimal toxicity, thus positioning them as highly promising candidates for a wide range of biological applications, including wound healing.


Assuntos
Benzoquinonas , Infertilidade , Nanofibras , Humanos , Nanofibras/química , Ácido 3-Hidroxibutírico , Cicatrização , Antibacterianos/farmacologia
8.
Indian J Community Med ; 49(1): 199-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425975

RESUMO

Background: Smartphone addiction among young adults is a growing concern that is often underestimated despite its significant health hazards. The objective of this study was to assess the extent of smartphone addiction and its association with physical activity level, anthropometric indices, and quality of sleep in young adults. Material and Methods: This cross-sectional study was conducted among 138 allied health sciences undergraduates of a tertiary care medical school in Puducherry, South India. The participants' extent of smartphone addiction, physical activity, and sleep quality were assessed using the Smartphone Addiction Scale (SAS), International Physical Activity Questionnaire, and Pittsburgh Sleep Quality Index (PSQI), respectively. Anthropometric indices (body mass index [BMI], waist-to-hip [W: H] ratio, waist-to-height [W: Ht] ratio, Conicity Index, and A Body Shape Index [ABSI]) were also measured following standardized procedures. Correlations between smartphone addiction, physical activity, anthropometric indices, and sleep quality were evaluated using Pearson's/Spearman's rank correlation coefficient. P <0.05 was considered statistically significant. Result: Over 50% of participants showed smartphone addiction and poor sleep quality. Although a significant negative correlation was observed between SAS scores and physical activity levels, significant positive correlations were noted between SAS scores and BMI and SAS and PSQI scores. Conclusion: Smartphone addiction is associated with decreased physical activity, increased BMI, and poor sleep quality in young adults.

9.
Perioper Med (Lond) ; 13(1): 13, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439069

RESUMO

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

10.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339130

RESUMO

Obstructive sleep apnea (OSA), a respiratory sleep disorder associated with cardiovascular diseases, is more prevalent in men. However, OSA occurrence in pregnant women rises to a level comparable to men during late gestation, creating persistent effects on both maternal and offspring health. The exact mechanisms behind OSA-induced cardiovascular diseases remain unclear, but inflammation and oxidative stress play a key role. Animal models using intermittent hypoxia (IH), a hallmark of OSA, reveal several pro-inflammatory signaling pathways at play in males, such as TLR4/MyD88/NF-κB/MAPK, miRNA/NLRP3, and COX signaling, along with shifts in immune cell populations and function. Limited evidence suggests similarities in pregnancies and offspring. In addition, suppressing these inflammatory molecules ameliorates IH-induced inflammation and tissue injury, providing new potential targets to treat OSA-associated cardiovascular diseases. This review will focus on the inflammatory mechanisms linking IH to cardiovascular dysfunction in males, pregnancies, and their offspring. The goal is to inspire further investigations into the understudied populations of pregnant females and their offspring, which ultimately uncover underlying mechanisms and therapeutic interventions for OSA-associated diseases.


Assuntos
Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Masculino , Animais , Humanos , Feminino , Gravidez , Doenças Cardiovasculares/complicações , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Imunidade , Inflamação/metabolismo
11.
Disabil Rehabil Assist Technol ; : 1-13, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385777

RESUMO

Objectives: The ability to localize sound sources is crucial for everyday listening, as it contributes to spatial awareness and the detection of warning signs. Individuals with hearing impairment have poorer localization abilities, which further deteriorate when they are fitted with a hearing aid. Although numerous studies have addressed this phenomenon, there is a lack of systematic evidence. The aim of the current systematic review is to address the following research question, "Do behavioural measures of spatial hearing ability improve with bilateral hearing aid fitting compared to the unaided hearing condition?"Design: A comprehensive search was conducted by two independent authors utilizing electronic databases, using various electronic databases, covering the period of 1965 to 2022. The inclusion and exclusion criteria were formulated using the Population, Intervention, Compression, Outcome, and Study design (PICOS) format, and the certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines.Results: The comprehensive search resulted in 2199 studies, 17 studies for qualitative synthesis and 15 studies for quantitative synthesis. The collected data was divided into two groups, namely vertical and horizontal localization. The results of the quantitative analysis indicate that the localization performance was significantly better in the unaided condition for both vertical and horizontal planes. The certainty of our evidence was judged to be moderate, meaning that "we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different".Conclusion: The review findings demonstrate that the bilateral fitting of the hearing aid did not effectively preserve spatial cues, which resulted in poorer localization performance irrespective of the plane of assessment.Review Registration: Prospective Register of Systematic Reviews (PROSPERO); CRD42022358164.


Hearing aids are a widely used rehabilitative method to compensate for the loss of audibility in individuals with hearing impairment. The current review highlights that, even though hearing aids can enhance audibility, they often fail to preserve spatial cues.This review paper provides a comprehensive summary of the existing literature, focusing on the preservation of spatial cues by hearing aids and the technologies that can enhance localization performance to a certain degree.The findings of the current study encourage both researchers and hearing aid manufacturers to advance their research methods pertaining to the preservation of spatial cues. This advancement has the potential to improve spatial awareness and possibly improve speech perception in the presence of noise in hearing aid users.

13.
BMJ Case Rep ; 17(1)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38233005

RESUMO

A wide range of inherited and acquired conditions can manifest as infantile erythroderma, among which CARD14-associated papulosquamous eruption (CAPE) is a rare cause. An infant boy presented with a psoriasiform rash that progressed to erythroderma and was unresponsive to topical steroids and cyclosporine. The early onset of the disease, its severity and resistance to conventional treatment were suggestive of a genetic cause. Genetic evaluation revealed a homozygous CARD14 variant of uncertain significance establishing the diagnosis of CAPE, and his parents were heterozygous carriers. There was only minimal improvement in the condition with supportive management and treatment with acitretin. Unfortunately, the child succumbed to sepsis and metabolic complications following a sudden worsening of skin disease. This case highlights the significance of genetic studies in diagnosing treatment-refractory cases of infantile erythroderma and emphasises the importance of early recognition of this rare condition.


Assuntos
Dermatite Esfoliativa , Lactente , Masculino , Criança , Humanos , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/genética , Acitretina , Ciclosporina , Guanilato Ciclase , Proteínas de Membrana , Proteínas Adaptadoras de Sinalização CARD
14.
Indian J Pediatr ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163829

RESUMO

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The International League of Associations for Rheumatology (ILAR) has defined JIA as "arthritis of unknown etiology persisting for ≥6 wk with an onset at <16 y of age, after excluding other causes of joint inflammation". Synovial inflammation is the result of a complex interplay of aberrant immune systems (both adaptive and innate) in a genetically susceptible individual, with possible external stimuli/triggers. Diagnosis of JIA essentially remains clinical, and laboratory investigations usually help to assess the severity of disease activity. Few investigations like antinuclear antibodies (ANA), human leukocyte antigen (HLA)-B27, and rheumatoid factor (RF) help to categorize or prognosticate a child with JIA. Timely use of effective therapeutic interventions including biological has shown good long-term outcomes of JIA.

15.
Autophagy ; 20(1): 166-187, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37642583

RESUMO

ABBREVIATIONS: AD: Alzheimer disease; APP: amyloid beta precursor protein; ATG: autophagy related; Aß: amyloid-ß; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; EEA1: early endosome antigen 1; FA: formic acid; GFP: green fluorescent protein; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP2: microtubule-associated protein 2; nmAß: non-modified amyloid-ß; npAß: non-phosphorylated amyloid-ß; pAß: phosphorylated amyloid-ß; p-Ser26Aß: amyloid-ß phosphorylated at serine residue 26; p-Ser8Aß: amyloid-ß phosphorylated at serine residue 8; RAB: RAB, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestome 1; YFP: yellow fluorescent protein.


Assuntos
Peptídeos beta-Amiloides , Autofagia , Autofagia/fisiologia , Peptídeos beta-Amiloides/metabolismo , Fosforilação , Proteínas de Fluorescência Verde/metabolismo , Lisossomos/metabolismo , Serina
17.
Biol Reprod ; 110(1): 185-197, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-37823770

RESUMO

Obstructive sleep apnea is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia, a hallmark of obstructive sleep apnea, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague-Dawley rats were subjected to normoxia (control), mild intermittent hypoxia (10.5% O2), or severe intermittent hypoxia (6.5% O2) from gestational days 10-21. Blood pressure was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mild and severe intermittent hypoxia groups demonstrated elevated blood pressure, reduced plasma nitrate/nitrite, and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor and phosphorylated endothelial nitric oxide synthase, while the levels of endothelin type A receptor and total endothelial nitric oxide synthase remained unchanged following intermittent hypoxia exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mild and severe intermittent hypoxia rats. However, mild and severe intermittent hypoxia rats exhibited impaired endothelium-dependent vasorelaxation responses to endothelin type B receptor agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in endothelin type B receptor-mediated relaxation. Treatment with IRL-1620 during intermittent hypoxia exposure significantly attenuated intermittent hypoxia-induced hypertension in pregnant rats. This was associated with elevated circulating nitrate/nitrite levels, enhanced endothelin type B receptor expression, increased endothelial nitric oxide synthase activation, and improved vasodilation responses. Our data suggested that intermittent hypoxia exposure during gestation increases blood pressure in pregnant rats by suppressing endothelin type B receptor-mediated signaling, providing a molecular mechanism linking intermittent hypoxia and gestational hypertension.


Assuntos
Hipertensão Induzida pela Gravidez , Apneia Obstrutiva do Sono , Humanos , Gravidez , Feminino , Ratos , Animais , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Endotelina-1/metabolismo , Endotelina-1/farmacologia , Hipertensão Induzida pela Gravidez/etiologia , Hipertensão Induzida pela Gravidez/metabolismo , Nitratos/metabolismo , Nitratos/farmacologia , Nitritos/metabolismo , Nitritos/farmacologia , Vasodilatação , Endotelinas/metabolismo , Endotelinas/farmacologia , Hipóxia/metabolismo , Receptor de Endotelina A/metabolismo , Artérias Mesentéricas , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Endotélio Vascular
18.
Virology ; 589: 109890, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37951086

RESUMO

Two recent studies documented the genome of a novel, extremely large (35.9 kb), nidovirus in RNA sequence databases from the marine neural model Aplysia californica. The goal of the present study was to document the distribution and transcriptional dynamics of this virus, Aplysia abyssovirus 1 (AAbV), in maricultured and wild animals. We confirmed previous findings that AAbV RNA is widespread and reaches extraordinary levels in apparently healthy animals. Transmission electron microscopy identified viral replication factories in ciliated gill epithelial cells but not in neurons where viral RNA is most highly expressed. Viral transcripts do not exhibit evidence of discontinuous RNA synthesis as in coronaviruses but are consistent with production of a single leaderless subgenomic RNA, as in the Gill-associated virus of Penaeus monodon. Splicing patterns in chronically infected adults suggested high levels of defective genomes, possibly explaining the lack of obvious disease signs in high viral load animals.


Assuntos
Aplysia , Nidovirales , Animais , Aplysia/genética , Nidovirales/genética , RNA Viral/genética , Microscopia Eletrônica de Transmissão
19.
Placenta ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37977936

RESUMO

Maternal vascular adaptations to establish an adequate blood supply to the uterus and placenta are essential for optimal nutrient and oxygen delivery to the developing fetus in eutherian mammals, including humans. Numerous factors contribute to maintaining appropriate hemodynamics and placental vascular development throughout pregnancy. Failure to achieve or sustain these pregnancy-associated changes in women is strongly associated with an increased risk of antenatal complications, such as preeclampsia, a hypertensive disorder of pregnancy. The precise etiology of preeclampsia is unknown, but emerging evidence points to a potential role for androgens. The association between androgens and maternal cardiovascular and placental function merits particular attention due to the notable 2- to 3-fold elevated plasma testosterone (T) levels observed in preeclampsia. T levels in preeclamptic women positively correlate with vascular dysfunction, and preeclampsia is associated with increased androgen receptor (AR) levels in placental tissues. Moreover, animal studies replicating the pattern and magnitude of T increase observed in preeclamptic pregnancies have reproduced key features of preeclampsia, including gestational hypertension, endothelial dysfunction, heightened vasoconstriction to angiotensin II, impaired spiral artery remodeling, placental hypoxia, reduced nutrient transport, and fetal growth restriction. Collectively, these findings suggest that AR-mediated activity plays a significant role in the clinical presentation of preeclampsia. This review critically evaluates this hypothesis, considering both clinical and preclinical evidence.

20.
J Environ Sci Public Health ; 7(4): 164-175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920428

RESUMO

Perfluorooctane sulfonate (PFOS), a synthetic chemical used in various commercial applications and industrial settings, has led to contamination of drinking water and has been detected in the bloodstream of pregnant women with gestational complications. Recent investigations have indicated that PFOS disrupts placental function; however, the mechanism remains elusive. Given the significant abundance of mitochondria in the placenta, which play a pivotal role in fulfilling the heightened energy requirements of pregnancy, our research aimed to examine the repercussions of PFOS exposure on mitochondrial dynamics within placental trophoblasts. Specifically, human trophoblasts (HTR-8/SVneo) were exposed to environmentally relevant concentrations of PFOS ranging from 0.1 to 50 µM for 48 hours. Findings revealed that PFOS exposure elicited a concentration-dependent decrease in basal, maximal, and ATP-linked respiration. PFOS inhibited the activity of electron transport complexes I, II, and III, resulting in diminished ATP production. Furthermore, PFOS reduced mitochondrial DNA copy number, indicating less mitochondrial content. Concurrently, there was a downregulation in the expression of mitochondrial biogenesis-related genes, including PGC-1α, NRF1, and NRF2. Notably, PFOS perturbed mitochondrial dynamics by suppressing the expression of fission-related genes (FIS1 and DRP1) and fusion-related genes (MFN1 and MFN2). In summary, our findings suggest that PFOS exposure leads to a decline in mitochondrial content and compromises the bioenergetic capacity of trophoblasts by impairing cellular respiration. This reduction in mitochondrial biogenesis and alterations in fission/fusion dynamics induced by PFOS may contribute to mitochondrial dysfunction in trophoblasts. Consequently, strategies that preserve mitochondrial function in trophoblasts may mitigate PFOS-induced impairment of placental energy metabolism.

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