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1.
Appl Microbiol Biotechnol ; 106(9-10): 3599-3610, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35590081

RESUMO

A novel ß-galactosidase gene (galM) was cloned from an aquatic habitat metagenome. The analysis of its translated sequence (GalM) revealed its phylogenetic closeness towards Verrucomicrobia sp. The sequence comparison and homology structure analysis designated it a member of GH42 family. The three-dimensional homology model of GalM depicted a typical (ß/α)8 TIM-barrel containing the catalytic core. The gene (galM) was expressed in a heterologous host, Escherichia coli, and the purified protein (GalM) was subjected to biochemical characterization. It displayed ß-galactosidase activity in a wide range of pH (2.0 to 9.0) and temperature (4 to 60 °C). The heat exposed protein showed considerable stability at 40 and 50 °C, with the half-life of about 100 h and 35 h, respectively. The presence of Na, Mg, K, Ca, and Mn metals was favorable to the catalytic efficiency of GalM, which is a desirable catalytic feature, as these metals exist in milk. It showed remarkable tolerance of glucose and galactose in the reaction. Furthermore, GalM discerned transglycosylation activity that is useful in galacto-oligosaccharides' production. These biochemical properties specify the suitability of this biocatalyst for milk and whey processing applications. KEY POINTS: • A novel ß-galactosidase gene was identified and characterized from an aquatic habitat. • It was active in extreme acidic to mild alkaline pH and at cold to moderate temperatures. • The ß-galactosidase was capable to hydrolyze lactose in milk and whey.


Assuntos
Leite , Soro do Leite , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Galactose/metabolismo , Concentração de Íons de Hidrogênio , Lactose/metabolismo , Leite/metabolismo , Oligossacarídeos/metabolismo , Filogenia , Soro do Leite/metabolismo , beta-Galactosidase/metabolismo
2.
Int J Neurosci ; 132(10): 985-993, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33272086

RESUMO

BACKGROUND: Migraine is often associated with psychiatric and emotional co-morbidities. Several studies have shown association of sleep problems and/or emotional co-morbidities among migraineurs. However, less is known about the association of migraine disability with sleep and emotional co-morbidities. OBJECTIVE: To explore the association of emotional co-morbidities and sleep quality with migraine disability among migraineurs in the central part of India. METHODS AND MATERIAL: A cross-sectional study enrolling 132 patients of migraine was conducted at a tertiary care centre. They were evaluated for migraine disability by Migraine Disability Assessment Test (MIDAS), emotional co-morbidities by depression, anxiety, stress scale (DASS-21) and sleep quality by Pittsburgh Sleep Quality Index (PSQI). RESULT: Mean age of participants was 32.9 ± 9.8 and 83.3% (n = 110) were females. Fourty seven percentage(n = 62) patients reported moderate to severe disability on MIDAS. Anxiety was most frequent (n = 87; 65.9%) emotional co-morbidity followed by depression (n = 70;53%) and stress (n = 52;39.4%). Severity of emotional co-morbidities increased while sleep quality deteriorated with increasing migraine disability. However, migraine frequency had positive correlation only with sleep quality. Stress showed a linear relationship with migraine disability at highest second-third decile of MIDAS. CONCLUSION: Migraineurs in central India have higher emotional co-morbidities. These co-morbidities increased and sleep quality deteriorated with increasing migraine disability. Frequency of migraine has no association with emotional co-morbidities. Linear association of stress at higher migraine disability prompts possible role of stress management to break the complex relationship between stress and migraine.


Assuntos
Transtornos de Enxaqueca , Ansiedade/complicações , Ansiedade/epidemiologia , Estudos Transversais , Emoções , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/psicologia , Sono , Inquéritos e Questionários
3.
Ecol Indic ; 111: 106020, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32372880

RESUMO

Ecological perturbations caused by biotic invasion have been identified as a growing threat to global sustainability. Invasive alien plants species (IAPS) are considered to be one of the major drivers of biodiversity loss and thereby altering the ecosystem services and socio-economic conditions through different mechanisms. Although the ecological impacts of IAPS are well documented, there is a dearth of studies regarding their economic quantification, livelihood considerations, biotechnological prospects (phytoremediation, bioenergy, phyto-synthesis of nanoparticles, biomedical, industrial applications etc.) and human health risk assessments of IAPS. In this context, the current panoramic review aimed to investigate the environmental, socio-ecological and health risks posed by IAPS as well as the compounded impact of IAPS with habitat fragmentation, climate and land use changes. To this end, the need of an integrated trans-disciplinary research is emphasized for the sustainable management of IAPS. The management prospects can be further strengthened through their linkage with geo-spatial technologies (remote sensing and GIS) by mapping and monitoring the IAPS spread. Further, the horizon of IAPS management is expanded to ecological indicator perspectives of IAPS, biosecurity, and risk assessment protocols with critical discussion. Moreover, positive as well as negative implications of the IAPS on environment, health, ecosystem services and socio-economy (livelihood) are listed so that a judicious policy framework could be developed for the IAPS management in order to mitigate the human health implications.

4.
Brain ; 140(4): 940-952, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334956

RESUMO

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.


Assuntos
Encéfalo/crescimento & desenvolvimento , Proteínas de Transporte/genética , Deficiências do Desenvolvimento/genética , Microcefalia/genética , Adolescente , Diferenciação Celular/genética , Movimento Celular/genética , Córtex Cerebral/crescimento & desenvolvimento , Criança , Pré-Escolar , Citoesqueleto/genética , Citoesqueleto/ultraestrutura , Feminino , Genes Recessivos , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Lactente , Masculino , Microtúbulos/genética , Microtúbulos/ultraestrutura , Mutação/genética , Linhagem , Monoéster Fosfórico Hidrolases , Adulto Jovem
5.
Phys Chem Chem Phys ; 17(32): 20741-53, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26206553

RESUMO

Ferroelectric BaTiO3 became a multifunctional material via doping of lanthanide ions (0.3 mol% Er(3+)/3.0 mol% Yb(3+)) and subsequently upconversion luminescence was enhanced by incorporation of Zn(2+) ions. Upconversion luminescence of BaTiO3:Er(3+)/Yb(3+) perovskite nanophosphor has been studied using 800 and 980 nm laser excitations. The emission dynamics is studied with respect to its dependence on input power and external temperature including lifetime. Based on time-resolved spectroscopy, it is inferred that two types of Er(3+) sites are present in the barium titanate lattice. The first one is a short lived component (minor species) present at 6-coordinated Ti-sites of low symmetry while the second one is a long lived component (major species), present at 12-coordinated Ba-sites with high symmetry. The influence of the introduction of Zn(2+) ions on the lifetime of (4)S3/2 and (4)F9/2 levels of Er(3+) ions is also investigated. Enhanced temperature sensing performance (120 K to 505 K) of the material is observed using the fluorescence intensity ratio technique, employing the emission from the thermally coupled, (2)H11/2 and (4)S3/2 energy levels of Er(3+) ions. The defect luminescence of the material is also found to increase upon Zn-doping.


Assuntos
Compostos de Bário/química , Érbio/química , Nanopartículas/química , Temperatura , Titânio/química , Itérbio/química , Zinco/química , Íons/química , Luminescência , Tamanho da Partícula , Propriedades de Superfície
6.
Indian J Otolaryngol Head Neck Surg ; 76(4): 3543-3547, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39130350

RESUMO

INTRODUCTION: Lymphangioma is a malformation of superficial lymphatic vessels. Tongue lymphangiomas are relatively uncommon. Multiple treatment modalities have been reported, with variable treatment responses. Most of the traditional treatment modalities have a high recurrence rate. CASE REPORT: We describe the use of coblation in the management of lymphangioma circumscriptum of the dorsum of tongue in two patients. Radiofrequency ablation of oral lymphangiomas showed early postoperative oral intake and minimal postoperative pain. There was no recurrence of disease on 1 year follow up. CONCLUSION: Improved wound healing, early postoperative oral intake and minimal postoperative pain, make radiofrequency ablation a highly valuable treatment modality for oral lymphangiomas and may be recommended as the treatment of choice.

7.
Int J Pharm ; 660: 124311, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38848798

RESUMO

The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation's shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.


Assuntos
Apoptose , Liberação Controlada de Fármacos , Ácido Glicirrízico , Ácido Hialurônico , Metotrexato , Neoplasias Bucais , Nanofibras , Ácido Hialurônico/química , Nanofibras/química , Animais , Metotrexato/administração & dosagem , Metotrexato/química , Metotrexato/farmacologia , Neoplasias Bucais/tratamento farmacológico , Humanos , Ácido Glicirrízico/química , Ácido Glicirrízico/administração & dosagem , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Masculino , Portadores de Fármacos/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia
8.
Curr Pharm Des ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38963114

RESUMO

INTRODUCTION: Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 µg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. METHODS: This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. RESULTS: Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. CONCLUSION: Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.

9.
J Biomol Struct Dyn ; 41(19): 9382-9388, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36376022

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by persistent challenges in social interactions and repetitive behavioral patterns. It is a significant problem emerging worldwide, as one in 100 children is affected by this disorder globally. In this study, a meta-analysis was performed for the identification of differentially expressed genes (DEGs) along with the expression analysis of regulatory genes. Functional enrichment analysis was an integral part of current findings to notify the significant pathways of this complex disorder. The study was conducted with two RNA-Seq datasets, viz., GSE64018 and GSE62098, for ASD patients and control samples from the GEO database. The identification of up-regulatory and down-regulatory genes was performed by the interaction analysis of transcription factors (TF) and DEGs. As an outcome of the meta-analysis, 2543 DEGs were identified as common across both of the datasets in which 1402 DEGs exhibited upregulation and 1130 genes have shown downregulation. In network analysis, upregulatory genes have shown strong interaction while downregulatory genes exhibit weak or null interaction. Further, in the enrichment analysis of screened upregulatory DEGs, three major significant pathways were identified namely the ATP synthesis pathway, FAS signaling pathway, and the Huntington's disease pathway. The common expression of CYC 1 gene in all the identified pathways has indicated that it is an important key regulator gene for the majorly associated pathways. The study concludes that all the potential DEGs were found to show their related high expression in neurobiological regulations specifically with ASD.Communicated by Ramaswamy S. Sarma.


Assuntos
Transtorno do Espectro Autista , Transcriptoma , Criança , Humanos , Transcriptoma/genética , Transtorno do Espectro Autista/genética , Redes Reguladoras de Genes , Encéfalo/metabolismo , Genes Reguladores , Perfilação da Expressão Gênica , Biologia Computacional
10.
Food Chem ; 421: 136130, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37116444

RESUMO

The study aims to enhance the functional properties of soybean meal (SBM) using potent proteolytic Bacillus strains isolated from kinema, a traditional fermented soybean product of Sikkim Himalaya. Selected Bacillus species; Bacillus licheniformis KN1G, B. amyloliquifaciens KN2G, B. subtilis KN36D, B. subtilis KN2B, and B. subtilis KN36D were employed for solid state fermentation (SSF) of SBM samples. The water and methanol extracts of SBM hydrolysates presented a significant increase in antioxidant activity. The water-soluble extracts of B. subtilis KN2B fermented SBM exhibited the best DPPH radical scavenging activity of 2.30 mg/mL. In contrast, the methanol-soluble extract of B. licheniformis KN1G fermented SBM showed scavenging activity of 0.51 mg/mL. Proteomic analysis of fermented soybean meal revealed several common and unique peptides produced by applying different starter cultures. Unique antioxidant peptides (HFDSEVVFF and VVDMNEGALFLPH) were identified from FSBM via LC/MS. B. subtilis KN36D showed the highest diversity of peptides produced during fermentation. The results indicate the importance of specific strains for fermentation to upgrade the nutritional value of raw fermented biomass.


Assuntos
Bacillus , Alimentos Fermentados , Metanol , Proteômica , Glycine max/química , Peptídeos , Peptídeo Hidrolases , Fermentação , Extratos Vegetais
11.
J Biol Dyn ; 17(1): 2206859, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37134223

RESUMO

Here, we investigate a mathematical model to assess the impact of disinfectants in controlling diseases that spread in the population via direct contacts with the infected persons and also due to bacteria present in the environment. We find that the disease-free and endemic equilibria of the system are related via a transcritical bifurcation whose direction is forward. Our numerical results show that controlling the transmissions of disease through direct contacts and bacteria present in the environment can help in reducing the disease prevalence. Moreover, fostering the recovery rate and the death rate of bacteria play significant roles in disease eradication. Our numerical observations convey that reducing the bacterial density at the source discharged by the infected population through the use of chemicals has prominent effect in disease control. Overall, our findings manifest that the disinfectants of high quality can completely control the bacterial density and the disease outbreak.


Assuntos
Infecções Bacterianas , Desinfetantes , Humanos , Desinfetantes/farmacologia , Modelos Biológicos , Modelos Teóricos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Surtos de Doenças
12.
J AOAC Int ; 106(5): 1305-1312, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37294736

RESUMO

BACKGROUND: Due to its medicinal properties, Pistacia integerrima is in high demand and is extensively used as a key ingredient in various formulations. However, its popularity has led to its inclusion on the International Union for Conservation of Nature threatened category list. In Ayurvedic texts, such as Bhaishajaya Ratnavali, Quercus infectoria is recommended as a substitute for P. integerrima in different formulations. Additionally, Yogratnakar highlights that Terminalia chebula shares similar therapeutic properties with P. integerrima. OBJECTIVE: The objective of the current study was to gather scientific data on metabolite profiling and marker-based comparative analysis of Q. infectoria, T. chebula, and P. integerrima. METHODS: In present study, hydroalcoholic and aqueous extracts of all three plants were prepared and standardized for the comparative evaluation of secondary metabolites. TLC was carried out for the comparative fingerprinting of the extracts using chloroform-methanol-glacial acetic acid-water (60 + 8 + 32 + 10, by volume) as a solvent system. A fast, sensitive, selective, and robust HPLC method was developed to determine gallic acid and ellagic acid from both extracts of all three plants. The method was validated for precision, robustness, accuracy, LOD and LOQ as per the International Conference on Harmonization guidelines. RESULTS: The TLC analysis revealed the presence of several metabolites, and the pattern of metabolites in the plants exhibited a certain degree of similarity. A highly precise and reliable quantification technique was created for gallic acid and ellagic acid, operating within a linear concentration range of 81.18-288.22 µg/mL and 3.83-13.66 µg/mL, respectively. The correlation coefficients for gallic acid and ellagic acid were 0.997 and 0.996, indicating good linear relationships. The gallic acid content in all three plants ranged from 3.74 to 10.16% w/w, while the ellagic acid content ranged from 0.10 to 1.24% w/w. CONCLUSION: The study contributes to the scientific understanding of the metabolite profiles and comparative analysis of Q. infectoria, T. chebula, and P. integerrima. The findings provide valuable insights into the chemical composition of these plants and can be used for various applications in herbal medicine. HIGHLIGHTS: This pioneering scientific approach highlights the phytochemical similarities between Q. infectoria, T. chebula and P. integerrima.


Assuntos
Pistacia , Quercus , Terminalia , Ácido Gálico/análise , Ácido Elágico , Extratos Vegetais/análise , Terminalia/química , Pistacia/química , Padrões de Referência
13.
Gene ; 877: 147548, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37279863

RESUMO

GPER is a seven transmembrane G-protein-coupled estrogen receptor that mediates rapid estrogen actions. Large volumes of data have revealed its association with clinicopathological variables in breast tumors, role in epidermal growth factor (EGF)-like effects of estrogen, potential as a therapeutic target or a prognostic marker, and involvement in endocrine resistance in the face of tamoxifen agonism. GPER cross-talks with estrogen receptor alpha (ERα) in cell culture models implicating its role in the physiology of normal or transformed mammary epithelial cells. However, discrepancies in the literature have obfuscated the nature of their relationship, its significance, and the underlying mechanism. The purpose of this study was to assess the relationship between GPER, and ERα in breast tumors, to understand the mechanistic basis, and to gauge its clinical significance. We mined The Cancer Genome Atlas (TCGA)-BRCA data to examine the relationship between GPER and ERα expression. GPER mRNA, and protein expression were analyzed in ERα-positive or -negative breast tumors from two independent cohorts using immunohistochemistry, western blotting, or RT-qPCR. The Kaplan-Meier Plotter (KM) was employed for survival analysis. The influence of estrogen in vivo was studied by examining GPER expression levels in estrus or diestrus mouse mammary tissues, and the impact of 17ß-estradiol (E2) administration in juvenile or adult mice. The effect of E2, or propylpyrazoletriol (PPT, an ERα agonist) stimulation on GPER expression was studied in MCF-7 and T47D cells, with or without tamoxifen or ERα knockdown. ERα-binding to the GPER locus was explored by analysing ChIP-seq data (ERP000380), in silico prediction of estrogen response elements, and chromatin immunoprecipitation (ChIP) assay. Clinical data revealed significant positive association between GPER and ERα expression in breast tumors. The median GPER expression in ERα-positive tumors was significantly higher than ERα-negative tumors. High GPER expression was significantly associated with longer overall survival (OS) of patients with ERα-positive tumors. In vivo experiments showed a positive effect of E2 on GPER expression. E2 induced GPER expression in MCF-7 and T47D cells; an effect mimicked by PPT. Tamoxifen or ERα-knockdown blocked the induction of GPER. Estrogen-mediated induction was associated with increased ERα occupancy in the upstream region of GPER. Furthermore, treatment with 17ß-estradiol or PPT significantly reduced the IC50 of the GPER agonist (G1)-mediated loss of MCF-7 or T47D cell viability. In conclusion, GPER is positively associated with ERα in breast tumors, and induced by estrogen-ERα signalling axis. Estrogen-mediated induction of GPER makes the cells more responsive to GPER ligands. More in-depth studies are warranted to establish the significance of GPER-ERα co-expression, and their interplay in breast tumor development, progression, and treatment.


Assuntos
Receptor alfa de Estrogênio , Neoplasias Mamárias Animais , Animais , Feminino , Camundongos , Linhagem Celular Tumoral , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação ao GTP/genética , Neoplasias Mamárias Animais/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
14.
Front Physiol ; 14: 1292033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38054039

RESUMO

The space radiation (IR) environment contains high charge and energy (HZE) nuclei emitted from galactic cosmic rays with the ability to overcome current shielding strategies, posing increased IR-induced cardiovascular disease risks for astronauts on prolonged space missions. Little is known about the effect of 5-ion simplified galactic cosmic ray simulation (simGCRsim) exposure on left ventricular (LV) function. Three-month-old, age-matched male Apolipoprotein E (ApoE) null mice were irradiated with 137Cs gamma (γ; 100, 200, and 400 cGy) and simGCRsim (50, 100, 150 cGy all at 500 MeV/nucleon (n)). LV function was assessed using transthoracic echocardiography at early/acute (14 and 28 days) and late/degenerative (365, 440, and 660 days) times post-irradiation. As early as 14 and 28-days post IR, LV systolic function was reduced in both IR groups across all doses. At 14 days post-IR, 150 cGy simGCRsim-IR mice had decreased diastolic wall strain (DWS), suggesting increased myocardial stiffness. This was also observed later in 100 cGy γ-IR mice at 28 days. At later stages, a significant decrease in LV systolic function was observed in the 400 cGy γ-IR mice. Otherwise, there was no difference in the LV systolic function or structure at the remaining time points across the IR groups. We evaluated the expression of genes involved in hemodynamic stress, cardiac remodeling, inflammation, and calcium handling in LVs harvested 28 days post-IR. At 28 days post-IR, there is increased expression of Bnp and Ncx in both IR groups at the lowest doses, suggesting impaired function contributes to hemodynamic stress and altered calcium handling. The expression of Gals3 and ß-Mhc were increased in simGCRsim and γ-IR mice respectively, suggesting there may be IR-specific cardiac remodeling. IR groups were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). No lower threshold was determined using the observed dose-response curves. These findings do not exclude the possibility of the existence of a lower IR threshold or the presence of IR-induced cardiovascular disease (CVD) when combined with additional space travel stressors, e.g., microgravity.

15.
Hum Immunol ; 83(12): 808-817, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36229379

RESUMO

The progressive decline of the anatomical architecture and loss of functional integrity of an individual is aging. Accumulation of degenerative cellular and molecular changes in the aging cells increases the fragility at the cellular and molecular levels. It pushes towards age-associated diseases like Alzheimer's disease, hypertension, cancer, cardiovascular diseases, etc. The impaired T cell function in aging is a leading contributor to increased susceptibility to pathogens, minimized vaccine response, and skewed inflammation. Recent studies about the role of T cells in the remodelling of the immune system have provided ways to examine and explore aging puzzles and their correlation with T cell functions. Here we review the metabolic aspect of T cell function and its possible restoration. IL-7 and mTOR mediated pathways and their association with reactivation of effector T cell function could help understanding the dark side of the compromised adaptive immune system, particularly T cell response, in aging. Understanding these crucial fundamentals could help design and target new molecules to prevent loss of T cell functionality in aging.


Assuntos
Envelhecimento , Linfócitos T , Humanos , Idoso , Senescência Celular , Inflamação
16.
Immunol Res ; 70(4): 530-536, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35585420

RESUMO

Retinoic acid (RA) plays a role in the mounting immune response and controls several functions of the human body, including cholesterol homeostasis. The synthesis, uptake, and efflux of cellular cholesterol are significantly linked to the mammalian target of rapamycin complex-1 (mTORC1). Activation of mTORC1 promotes the synthesis and uptake of the cholesterol and suppresses its efflux, thus causing accumulation of cellular cholesterol. It is intriguing to know the effect of a high dose of RA on cholesterol accumulation in macrophages (mφ) and whether it is via mTOR activation. It is important to note that the long-term treatment of RA in humans is safe. Therefore, we chose a high dose of RA to observe its effect, which may be implicated in diseases like visceral leishmaniasis, where cholesterol deficiency is established. In the present study, we found the increased expression of RAPTOR, a regulatory component of the mTORC1 complex, in mφ upon treatment with RA. We observed the increased expression of SREBP2, LDLR, and PCSK9 in RA-treated mφ under sufficient cholesterol conditions, which further increased cellular cholesterol levels. Notably, their expressions were decreased when the mTOR pathway was inhibited by rapamycin. However, treatment with rapamycin did not result in the loss of cellular cholesterol in RA-treated mφ. Comparison with rapamycin-treated mφ suggests that RA induces cellular cholesterol levels in a mTORC1-independent manner.


Assuntos
Pró-Proteína Convertase 9 , Tretinoína , Colesterol , Humanos , Pró-Proteína Convertase 9/metabolismo , Proteína Regulatória Associada a mTOR/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Tretinoína/metabolismo , Tretinoína/farmacologia
17.
Cureus ; 14(11): e31575, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36540487

RESUMO

Persistent sciatic artery (PSA) aneurysms are a rare cause of gluteal or lower extremity pain. The persistent sciatic artery is an uncommon congenital vasculature anomaly that presents with variable clinical presentation and is prone to cause an aneurysm, thrombosis, rupture, and possible amputation. Thus, early diagnosis is imperative to prevent further complications. We present the case of a 75-year-old female who was diagnosed with a persistent sciatic artery aneurysm after presenting with gluteal and lower extremity pain initially thought to be sciatica. Our patient underwent a successful hybrid open and endovascular approach with a femoral to below-knee popliteal artery bypass and the placement of coils at the proximal and distal ends of the aneurysmal segment.

18.
Mol Clin Oncol ; 17(4): 143, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36157315

RESUMO

The expression of genes is altered in various diseases and is responsible for the disease's initiation, progression and pathology. Several other genes, predominantly inactivated, may become activated in a given condition and contribute to the initiation and progression of the disease. Similarly, human endogenous viruses (HERVs) are an incomplete, non-productive and inactive viral sequence present in the heterochromatin of the human genome, and are often referred to as junk DNA. HERVs were inserted into the host genome millions of years ago. However, they were silenced due to multiple mutations and recombination that occurred over time. However, their expression is increased in cancers due to either epigenetic or transcriptional dysregulation. Some of the HERVs having intact open reading frames have been reported to express virus-like particles, functional peptides and proteins involved in tumorigenesis. To summarize, there is involvement of different HERVs in the initiation and progression of several cancers. The present review aims to provide concise information on HERV and its involvement in the initiation and progression of multiple types of cancer.

19.
Cureus ; 14(11): e31140, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36479405

RESUMO

Eosinophilic fasciitis is an uncommon disorder presenting with diffuse fasciitis and peripheral eosinophilia. Due to the rarity of this disorder and limited literature, its diagnosis and treatment are often delayed. We present the case of a young male wherein the diagnosis of eosinophilic fasciitis was initially delayed due to an atypical presentation. However, after the diagnosis was confirmed, the patient was successfully managed with oral corticosteroids. A well-written informed consent was obtained from the patient prior to the preparation of this manuscript. An 18-year-old right-hand dominant male presented with a sudden onset, progressive, non-traumatic, left forearm swelling associated with a weak hand grip. The swelling was tender on examination with a local rise in temperature. Radiographs taken at the time of presentation revealed no osseous pathology. As the initial blood investigations were suggestive of a localized inflammatory pathology involving the forearm, the patient was managed with non-steroidal anti-inflammatory drugs and analgesics. He returned 6 months later with a recurrence of the symptoms. A magnetic resonance imaging scan of the left forearm was performed to further investigate the pathology and it was suggestive of a diffuse plaque-like thickening involving the myofascial layer of the muscles. Blood investigations showed peripheral eosinophilia, raised immunoglobulin G count, and raised inflammatory markers. A full-thickness forearm biopsy showed the presence of lymphocytic infiltration. A diagnosis of eosinophilic fasciitis was suspected and the patient was managed with oral corticosteroids, given as a tapering dose. Following this, the patient had symptomatic improvement with the resolution of the deranged blood parameters. He was asymptomatic at the latest follow-up of 4 years.

20.
Food Chem X ; 13: 100231, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35499015

RESUMO

In this study, simulated in vitro GI digestion of the Himalayan hard chhurpi cheese resulted in the increase of hydrolyzed protein content, antioxidant and ACE-inhibitory activities. LC-MS/MS-based peptidomics revealed a total of 1473 peptides in the samples originating from different milk proteins, including α-S1-casein, α-S2-casein, ß-casein, κ-casein, α-lactalbumin, and ß-lactoglobulin, out of which 60 peptides have been reported for different functional properties. A total of 101 peptides were predicted to be antihypertensive using the bioactivity prediction web servers, AHTpin and mAHTPred. In silico molecular docking studies predicted 20 antihypertensive peptides, exhibiting non-bond interactions between hard chhurpi peptides and ACE catalytic residues. A peptide, SLVYPFPGPI, identified in GI digested cow hard chhurpi and undigested, and GI digested samples of yak hard chhurpi, showed a stronger binding affinity towards ACE. Identifying antioxidant and ACE inhibitory peptides in hard cheese products adds value to them as functional foods of the Himalayan region.

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