Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 463
Filtrar
1.
JAMA ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985542

RESUMO

This JAMA Insights explores the adverse effects of wildfires on human health and health care systems and offers suggestions on how clinicians can help mitigate the health threats posed by wildfires.

2.
Nat Commun ; 15(1): 5173, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890352

RESUMO

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.


Assuntos
Modelos Animais de Doenças , Bainha de Mielina , Oligodendroglia , Infecção por Zika virus , Zika virus , Animais , Infecção por Zika virus/virologia , Infecção por Zika virus/patologia , Oligodendroglia/virologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Feminino , Bainha de Mielina/metabolismo , Gravidez , Zika virus/patogenicidade , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/patologia , Macaca nemestrina , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/metabolismo , Humanos , Proteína Básica da Mielina/metabolismo , Proteína Básica da Mielina/genética
3.
Pediatr Dev Pathol ; 27(3): 241-254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549265

RESUMO

BACKGROUND: The unexpected observation of calretinin immunoreactivity in smooth muscle cells in the muscularis propria of the cecum led to a more detailed examination of calretinin expression and its possible relationship to propulsive contractile activity around the vermiform appendix. METHODS: Immunohistochemistry and RNA in situ hybridization were performed to analyze calretinin expression in intestinal samples from 33 patients at ages ranging from mid-gestation fetuses to adults, as well as in some potentially relevant animal models. Dual immunolabeling was done to compare calretinin localization with markers of smooth muscle and interstitial cells of Cajal. RESULTS: Calretinin expression was observed consistently in the innermost smooth muscle layers of the muscularis interna in the human cecum, appendiceal base, and proximal ascending colon, but not elsewhere in the intestinal tract. Calretinin-positive smooth muscle cells did not co-express markers located in adjacent interstitial cells of Cajal. Muscular calretinin immunoreactivity was not detected in the ceca of mice or macaques, species which lack appendices, nor in the rabbit cecum or appendix. CONCLUSIONS: Localized expression of calretinin in cecal smooth muscle cells may reduce the likelihood of retrograde, calcium-mediated propulsive contractions from the proximal colon and suppress pro-inflammatory fecal stasis in the appendix.


Assuntos
Apendicite , Calbindina 2 , Ceco , Músculo Liso , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Pessoa de Meia-Idade , Coelhos , Adulto Jovem , Apendicite/genética , Apendicite/metabolismo , Apendicite/patologia , Apêndice/metabolismo , Apêndice/patologia , Calbindina 2/genética , Calbindina 2/metabolismo , Ceco/metabolismo , Imuno-Histoquímica , Músculo Liso/metabolismo
4.
J Healthc Eng ; 2024: 3733705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38223259

RESUMO

Osteoporosis is a word used to describe a condition in which bone density has been diminished as a result of inadequate bone tissue development to counteract the elimination of old bone tissue. Osteoporosis diagnosis is made possible by the use of medical imaging technologies such as CT scans, dual X-ray, and X-ray images. In practice, there are various osteoporosis diagnostic methods that may be performed with a single imaging modality to aid in the diagnosis of the disease. The proposed study is to develop a framework, that is, to aid in the diagnosis of osteoporosis which agrees to all of these CT scans, X-ray, and dual X-ray imaging modalities. The framework will be implemented in the near future. The proposed work, CBTCNNOD, is the integration of 3 functional modules. The functional modules are a bilinear filter, grey-level zone length matrix, and CB-CNN. It is constructed in a manner that can provide crisp osteoporosis diagnostic reports based on the images that are fed into the system. All 3 modules work together to improve the performance of the proposed approach, CBTCNNOD, in terms of accuracy by 10.38%, 10.16%, 7.86%, and 14.32%; precision by 11.09%, 9.08%, 10.01%, and 16.51%; sensitivity by 9.77%, 10.74%, 6.20%, and 12.78%; and specificity by 11.01%, 9.52%, 9.5%, and 15.84%, while requiring less processing time of 33.52%, 17.79%, 23.34%, and 10.86%, when compared to the existing techniques of RCETA, BMCOFA, BACBCT, and XSFCV, respectively.


Assuntos
Osteoporose , Humanos , Raios X , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Redes Neurais de Computação , Aprendizado de Máquina
5.
Pediatr Surg Int ; 40(1): 19, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38086970
6.
J Obstet Gynaecol India ; 73(Suppl 2): 234-239, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38143992

RESUMO

Aims and Objectives: To determine utilization of spot urinary albumin/creatinine ratio (UACR) to predict subsequent development of preeclampsia, measured between 17 and 24 weeks of gestational age in asymptomatic antenatal woman and determine their maternal and neonatal outcomes. Introduction: In preeclampsia the basic pathology is generalized endothelial dysfunction. It causes glomerular endotheliosis which leads to proteinuria, decreased glomerular filtration rate and renal blood flow. Thus microalbuminuria is an early marker which can measured to predict preeclampsia. Materials and Methods: It is a prospective observational study, carried out for one year in a cohort of asymptomatic antenatal women at 17-24 weeks of gestational age, attending hospital for routine antenatal check-up with a singleton pregnancy and no associated complications. Urine albumin and creatinine ratio (UACR) is measured at first visit, and women were followed till delivery and the maternal and foetal outcomes were recorded. Results: Out of 81 pregnant women enrolled in the study, 58% belonged to 18-25 years, 54.3% belonged to lower middle class. There was a significant difference in mean UACR among women who developed preeclampsia (PE) and gestational diabetes mellitus (GDM) with p value < 0.05. In the study there was significant association between severe PE, PE and GDM with UACR at 22 as cut-off, with p value < 0.05. In the study among those with UACR > 22, 2.5% had IUFD, 12.5% had LBW, and 7.5% were admitted to NICU. Conclusion: With the measurement of spot UACR in mid-trimester we can predict the development of preeclampsia before the onset of clinical manifestations. UACR > = 171 mg/g predicted preeclampsia well before the onset of clinical manifestations with high sensitivity of 83.3% and specificity of 98.6%. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-023-01862-9.

7.
bioRxiv ; 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37873381

RESUMO

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in non-microcephalic infants, of which the pathogenesis remains poorly understood. We utilized an established pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We found prenatal ZikV exposure led to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses revealed marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals showed multi-focal decompaction consistent with perturbation or remodeling of previously formed myelin, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.

8.
J Allergy Clin Immunol ; 152(3): 582-590, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295475

RESUMO

The epigenome is at the intersection of the environment, genotype, and cellular response. DNA methylation of cytosine nucleotides, the most studied epigenetic modification, has been systematically evaluated in human studies by using untargeted epigenome-wide association studies (EWASs) and shown to be both sensitive to environmental exposures and associated with allergic diseases. In this narrative review, we summarize findings from key EWASs previously conducted on this topic; interpret results from recent studies; and discuss the strengths, challenges, and opportunities regarding epigenetics research on the environment-allergy relationship. The majority of these EWASs have systematically investigated select environmental exposures during the prenatal and early childhood periods and allergy-associated epigenetic changes in leukocyte-isolated DNA and more recently in nasal cells. Overall, many studies have found consistent DNA methylation associations across cohorts for certain exposures, such as smoking (eg, aryl hydrocarbon receptor repressor gene [AHRR] gene), and allergic diseases (eg, EPX gene). We recommend the integration of both environmental exposures and allergy or asthma within long-term prospective designs to strengthen causality as well as biomarker development. Future studies should collect paired target tissues to examine compartment-specific epigenetic responses, incorporate genetic influences in DNA methylation (methylation quantitative trait locus), replicate findings across diverse populations, and carefully interpret epigenetic signatures from bulk, target tissue or isolated cells.


Assuntos
Epigenoma , Hipersensibilidade , Gravidez , Feminino , Humanos , Pré-Escolar , Estudo de Associação Genômica Ampla , Epigênese Genética , Hipersensibilidade/genética , Metilação de DNA
9.
J Psychosom Res ; 170: 111350, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37207550

RESUMO

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting mainly the skin. Chronic stress leads to the blunted hypothalamic-pituitary-adrenal axis (HPA) that might induce pro-inflammatory conditions. Hence, we assessed the blood levels of the HPA hormones and interleukin-17 (IL-17) and the effect of stress and emotional distress to understand the link between stress and psoriasis better. METHODS: This cross-sectional study included 45 patients with psoriasis and 45 age and gender-matched apparently healthy volunteers (n = 45). IL-17, cortisol, and adrenocorticotrophic hormone (ACTH) levels were assessed in both groups. Psoriasis Area Severity Index (PASI) was used to assess disease severity. Presumptive Stressful Life Events scale [PSLE], Perceived Stress scale [PSS] and Daily Hassles and Uplifts Scale [DHUS] scoring were used to assess stress levels and emotional distress. RESULTS: Patients with psoriasis had higher levels of IL-17 and ACTH and lower levels of cortisol, as compared to controls. Stress scores (PSS, PSLE & DHUS) were significantly elevated in cases, as compared to the controls. IL-17, ACTH and stress scores showed a significant positive correlation with one another and a significant negative correlation with cortisol levels. They also showed a significant positive correlation with PASI, while cortisol levels showed a significant negative correlation. CONCLUSION: Psoriasis patients having high ACTH, IL-17 and stress scores had lower levels of cortisol, indicating a dysregulated HPA axis with the pro-inflammatory state. This might lead to exacerbation of psoriatic flares, which needs investigation in further prospective studies.


Assuntos
Sistema Hipotálamo-Hipofisário , Psoríase , Humanos , Hidrocortisona , Interleucina-17 , Estudos Transversais , Estudos Prospectivos , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico , Inflamação
10.
Am J Ophthalmol ; 253: 206-214, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37044197

RESUMO

PURPOSE: To compare the utility of keratometry vs total keratometry (TK) for intraocular lens power calculations in eyes with keratoconus (KCN) using KCN and non-KCN formulae. DESIGN: Retrospective cohort study. METHODS: This study was conducted at 2 academic centers and included 87 eyes in 67 patients who underwent cataract surgery between 2019 and 2021. Biometry measurements were obtained using a swept-source optical coherence tomography biometer (IOL Master 700). Refractive prediction errors, including root mean square error (RMSE), were calculated for 13 formulae. These included 4 classical formulae (Haigis, Hoffer Q, Holladay 1 [H1], and SRK/T), 5 new formulae (NF) (Barrett Universal II [BU2], Cooke K6, EVO 2.0, Kane, and Pearl-DGS), 3 KCN formulae (BU2 KCN: M-PCA, BU2 KCN: P-PCA, and Kane KCN), and H1 with equivalent keratometry reading values (H1-EKR). Formulae were ranked by RMSE. Friedman analysis of variance with post hoc analysis and H-testing was used for statistical significance testing. RESULTS: KCN formulae had the lowest RMSEs in all eyes, and BU2 KCN:M-PCA performed the best among KCN formulae in all subgroups. In eyes with severe KCN, if TK values are unavailable, the BU2 KCN: P-PCA performed better than the top-ranked non-KCN formula (SRK/T). In eyes with nonsevere KCN, if TK values are unavailable, EVO 2.0 K was statistically superior to the next competitor (Kane K). H1-EKR had the highest RMSE. CONCLUSIONS: KCN formulae and TK are useful for intraocular lens power calculations in KCN eyes, especially in eyes with severe KCN. The BU2 KCN: M-PCA using TK values performed best for eyes with all severities of KCN. For eyes with nonsevere KCN, the EVO 2.0 TK or K can also be used.


Assuntos
Ceratocone , Lentes Intraoculares , Facoemulsificação , Erros de Refração , Humanos , Ceratocone/diagnóstico , Ceratocone/cirurgia , Implante de Lente Intraocular/métodos , Refração Ocular , Estudos Retrospectivos , Biometria/métodos , Óptica e Fotônica , Facoemulsificação/métodos , Comprimento Axial do Olho
11.
Artigo em Inglês | MEDLINE | ID: mdl-36767891

RESUMO

Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dermatite Atópica , Animais , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Estudos Transversais , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Pele/química , Material Particulado , Exposição Ambiental/efeitos adversos
12.
JAMA Netw Open ; 6(1): e2251553, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36637821

RESUMO

This cross-sectional study examines whether clinic visits and online search interest for psoriasis were associated with wildfire air pollution after a delayed lag period.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Psoríase , Incêndios Florestais , Humanos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Psoríase/epidemiologia , Assistência Ambulatorial
13.
Arch Dermatol Res ; 315(4): 1037-1039, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36308559

RESUMO

Epigenetic (or DNA methylation) age is calculated based on methylation of certain cytosine-guanine (CpG) repeats, and it can accurately estimate one's chronologic age. Importantly, epigenetic age acceleration (EAA) is highly predictive of age-associated morbidity and all-cause mortality. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with significant systemic disease burden. Here, we performed a pilot study to calculate EAA from formalin-fixed paraffin-embedded skin samples using Illumina Infinium MethylationEpic BeadChip arrays. Our results demonstrated no significant difference in intrinsic EAA among HS compared to controls (- 1.00 years, p-value = 0.52), significant increases in both extrinsic EAA (13.72 years, p-value < 0.001) and PhenoAge acceleration (7.72 years, p-value = 0.003), and a significant decrease in GrimAge acceleration (- 5.14 years, p-value < 0.001). Our findings suggest that the acceleration of epigenetic age in the HS skin may be associated with extrinsic immune-related changes and can potentially serve as a biomarker of the present and/or future disease burden in HS patients.


Assuntos
Hidradenite Supurativa , Humanos , Hidradenite Supurativa/genética , Epigênese Genética , Projetos Piloto , Metilação de DNA , Pele , Envelhecimento/genética
14.
Am J Obstet Gynecol ; 228(4): 463.e1-463.e20, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36126729

RESUMO

BACKGROUND: COVID-19 is caused by the SARS-CoV-2 virus and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology. However, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus. To what extent a SARS-CoV-2 infection of the placenta alters the placental antiviral innate immune response is not well understood. A dysregulated innate immune response in the setting of maternal COVID-19 disease may increase the risk of inflammatory tissue injury or placental compromise and may contribute to deleterious pregnancy outcomes. OBJECTIVE: We sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of 6 antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response. Our hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an up-regulated placental antiviral innate immune response. STUDY DESIGN: We performed a case-control study on placental tissues (chorionic villous tissues and chorioamniotic membrane) collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease. We performed real-time quantitative polymerase chain reaction and immunohistochemistry, and the placental histopathology was evaluated. Clinical data were abstracted. Fisher exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (<10 days since diagnosis) vs recovered COVID-19 (>10 days since diagnosis) at the time of delivery. Secondary regression models adjusted for labor status as a covariate and evaluated potential correlation between placental innate immune gene expression and other variables. RESULTS: SARS-CoV-2 viral RNA was detected in placental tissues from 5 women with COVID-19 and from no controls (0/24, 0%). Only 1 of 5 cases with detectable SARS-CoV-2 viral RNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells. We detected a considerably lower gene expression of 5 critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in the chorionic villi and chorioamniotic membranes from women with active or recovered COVID-19 than controls, which remained significant after adjustment for labor status. There were minimal correlations between placental gene expression and other studied variables including gestational age at diagnosis, time interval between COVID-19 diagnosis and delivery, prepregnancy body mass index, COVID-19 disease severity, or placental pathology. CONCLUSION: A maternal SARS-CoV-2 infection was associated with an impaired placental innate immune response in chorionic villous tissues and chorioamniotic membranes that was not correlated with gestational age at COVID-19 diagnosis, time interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity, or placental pathology.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Feminino , Gravidez , Humanos , Recém-Nascido , COVID-19/patologia , Placenta/metabolismo , SARS-CoV-2 , Antivirais/metabolismo , Teste para COVID-19 , Estudos de Casos e Controles , Complicações Infecciosas na Gravidez/diagnóstico , Nascimento Prematuro/metabolismo , Imunidade Inata , RNA Viral/metabolismo , Expressão Gênica , Transmissão Vertical de Doenças Infecciosas
15.
Qual Quant ; 57(1): 561-585, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35382094

RESUMO

The pandemic recession has caused enormous disturbances in many industrialized countries. The massive disruption of the supply chain of production is affecting manufacturing companies operating in and around India. Particularly the medium-sized bus body building works have been reduced, due to its compound anomalies. The integrated view of the production facility priorities is not an easy task. Since it is difficult for available labour to conduct an entire project, the completion of a production process is delayed. But still, the dilemma remains as to how production managers can correctly interpret the priorities of the facility. Indeed, this is a problem missing from the previous study. Fortunately, in the current competitive environment, it is essentially needed. This study has been used Back Propagation Neural Network (BPNN) approach for predicting production facility priorities. The experimental results confirm the suitability of the model for predicting priorities. A real-world problem is taken into account in making use of the model output. In this sense, this total solution facilitates production managers in assessing and enhancing the production facilities. The findings emphasize the priority of "equipment effectiveness, labour scheduling and communication" in order to strengthen the post-pandemic production facility.

16.
Int J Cardiol ; 372: 101-109, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36481261

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes with no known biomarkers for early detection. Mitochondria-associated endoplasmic reticulum membranes (MAM) are less studied subcellular targets but an emerging area for exploration in metabolic disorders including DCM. We herein studied the role of MAMs and downstream mitochondrial functions in DCM. We also explored the efficacy of ferulic acid (FeA) against DCM via modulation of MAM and its associated signaling pathway. METHODS: The H9c2 cardiomyoblast cells were incubated with high concentration (33 mM) of d-glucose for 48 h to create a high glucose ambience in vitro. The expression of various critical proteins of MAM, mitochondrial function, oxidative phosphorylation (OxPhos) and the genesis of apoptosis were examined. The rats fed with high fat/high fructose/streptozotocin (single dose, i.p.) were used as a diabetic model and analyzed the insulin resistance and markers of cardiac hypertrophy and apoptosis. RESULTS: High glucose conditions caused the upregulation of MAM formation via PACS2, IP3R2, FUNDC1, and VDAC1 and decreased mitochondrial biogenesis, fusion and OxPhos. The upregulation of mitochondria-driven SMAC-HTRA2-ARTS-XIAP apoptosis and other cell death pathways indicate their critical roles in the genesis of DCM at the molecular level. The diabetic rats also showed cardiomyopathy with increased heart mass index, TNNI3K, troponin, etc. FeA effectively prevented the high glucose-induced MAM alterations and associated cellular anomalies both in vitro and in vivo. CONCLUSION: High glucose-induced MAM distortion and subsequent mitochondrial dysfunctions act as the stem of cardiomyopathy. MAM could be explored as a potential target to treat diabetic cardiomyopathy. Also, the FeA could be an attractive nutraceutical agent for diabetic cardiomyopathy.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Ratos , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/farmacologia , Proteínas Reguladoras de Apoptose/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Glucose/toxicidade , Glucose/metabolismo , Proteínas de Membrana , Proteínas Mitocondriais/farmacologia , Miócitos Cardíacos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 1 Dependente de Voltagem/uso terapêutico , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo
17.
Pediatr Dev Pathol ; 26(1): 39-51, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36571289

RESUMO

BACKGROUND: Pathogenic mutations in the smooth muscle myosin heavy chain gene, MYH11, cause megacystis megacolon intestinal hypoperistalsis syndrome and other forms of chronic intestinal pseudo-obstruction. Evaluation of intestinal tissues from affected patients is often performed before mutational analysis, but the pathological findings of MYH11-variant visceral myopathy have not been well defined. METHODS: Light microscopic, immunohistochemical, and ultrastructural findings from multiple intestinal samples from 2 patients with MYH11-variant visceral myopathy were reviewed, including MYH11-specific immunohistochemistry. The findings were compared with intestinal samples from patients with gamma-smooth muscle actin (ACTG2)-variant visceral myopathy and non-pseudo-obstruction controls. RESULTS: Apart from non-specific changes (e.g., muscle hypertrophy and distension-related muscularis propria necrosis), no alterations were identified by routine histopathological evaluation or electron microscopy. Immunohistochemistry with antibodies against a battery of smooth muscle proteins, including MYH11, revealed indistinguishable patterns of immunoreactivity in the muscularis propria of both patients and controls. CONCLUSIONS: Myopathic morphological or immunohistochemical changes may not be present in intestinal specimens from patients with MYH11-variant visceral myopathy. Molecular genetic studies should be considered for patients with chronic intestinal pseudo-obstruction and normal or non-specific pathology findings.


Assuntos
Anormalidades Múltiplas , Doenças Fetais , Pseudo-Obstrução Intestinal , Feminino , Humanos , Colo/patologia , Anormalidades Múltiplas/patologia , Pseudo-Obstrução Intestinal/diagnóstico , Pseudo-Obstrução Intestinal/genética , Pseudo-Obstrução Intestinal/metabolismo , Mutação , Doenças Fetais/patologia , Actinas/genética , Cadeias Pesadas de Miosina/genética
18.
Cell Signal ; 104: 110579, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36572189

RESUMO

Eph receptors, the largest known family of receptor tyrosine kinases, and ephrin ligands have been implicated in a variety of human cancers. The novel bidirectional signaling events initiated by binding of Eph receptors to their cognate ephrin ligands modulate many cellular processes such as proliferation, metastasis, angiogenesis, invasion, and apoptosis. The relationships between the abundance of a unique subset of Eph receptors and ephrin ligands with associated cellular processes indicate a key role of these molecules in tumorigenesis. The combinatorial expression of these molecules converges on MAP kinase and/or AKT/mTOR signaling pathways. The intracellular target proteins of the initial signal may, however, vary in some cancers. Furthermore, we have also described the commonality of up- and down-regulation of individual receptors and ligands in various cancers. The current state of research in Eph receptors illustrates MAP kinase and mTOR pathways as plausible targets for therapeutic interventions in various cancers.


Assuntos
Neoplasias , Receptores da Família Eph , Humanos , Receptores da Família Eph/química , Receptores da Família Eph/metabolismo , Efrinas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ligantes , Neoplasias/metabolismo , Proteínas Quinases Ativadas por Mitógeno , Serina-Treonina Quinases TOR
19.
Front Cell Infect Microbiol ; 13: 1299644, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38239507

RESUMO

Background: Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints. Methods: Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests. Results: Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1ß, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05). Conclusion: Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.


Assuntos
Nascimento Prematuro , Infecções Estreptocócicas , Recém-Nascido , Animais , Humanos , Gravidez , Feminino , Streptococcus agalactiae/fisiologia , Placenta , Proteínas de Checkpoint Imunológico/metabolismo , Regulação para Cima , Cesárea , Infecções Estreptocócicas/patologia , Primatas
20.
J Healthc Eng ; 2022: 3376079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465249

RESUMO

Motivation. In the modern world of information technology, the need for ensuring the safety of wireless transmissions while transiting through a given network is growing rapidly. The process of transmitting images via a wireless network is fraught with difficulty. There is a possibility that data may be corrupted while being transmitted, which would result in an image with low resolution. Both of these issues were investigated head-on in this research methodology using the aiding double space-time block coding (DSTTD) system and the self-super-resolution (SSR) method. Description. In recent times, medical image transmission over a wireless network has received a significant amount of attention, as a result of the sharing of medical images between patients and doctors. They would want to make sure that the image was sent in a risk-free and protected manner. Arnold cat map, often known as ACM, is a well-known and widely implemented method of image transmission encryption that has been in use for quite some time. At the receiver end, SSR is now being employed in order to view the transmitted medical image in the finest possible resolution. It is anticipated that in the near future, image transmission through wireless DSTTD will be technically feasible. This is performed in order to maximize the benefits that the system has to offer in terms of both spatial diversity and multiplexing as much as is possible. Conclusion. The SSR approach is used in order to represent the image in a document pertaining to human resources. ACM is used so that the image may be sent in a risk-free and protected way. The adoption of a DSTTD-based architecture for wireless communication is suggested. A comparison of the results is provided, and PSNR and SSIM values are detailed towards the results and discussion of the article.


Assuntos
Tecnologia da Informação , Imageamento por Ressonância Magnética , Humanos , Projetos de Pesquisa , Comunicação , Ciência da Informação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...